opus4.kobv.de · v Danksagung Bei Herrn Prof. Dr. John A. Gladysz bedanke ich mich für den...

New Design Strategies for Phosphine Organocatalysts:

Enantioselective Processes involving

Chiral Rhenium Fragments

and

Recycling involving Perfluorinated Pony Tails

Den Naturwissenschaftlichen Fakultäten

der Friedrich-Alexander-Universität Erlangen-Nürnberg

zur

Erlangung des Doktorgrades

vorgelegt von

Florian O. Seidel

aus Nürnberg

ii

Als Dissertation genehmigt von den Naturwissenschaftlichen

Fakultäten der Universität Erlangen-Nürnberg.

Tag der mündlichen Prüfung: 21.01.2009

Vorsitzender der Promotionskommission: Prof. Dr. E. Bänsch

Erstberichterstatter: Prof. Dr. J. A. Gladysz

Zweitberichterstatter: Prof. Dr. H. Gröger

iii

meiner Familie

iv

Die vorliegende Arbeit wurde am Institut für Organische Chemie der Friedrich-Alexander-

Universität Erlangen-Nürnberg in der Zeit von Januar 2005 bis Dezember 2008 unter Anleitung von

Prof. Dr. John A. Gladysz angefertigt.

v

Danksagung

Bei Herrn Prof. Dr. John A. Gladysz bedanke ich mich für den wissenschaftlichen Anstoß

und die Betreuung dieser Arbeit, wobei maximaler Freiraum für die eigene Kreativität und den

Forscherdrang blieb. Weiterhin bedanke ich mich für die wohlwollende Förderung.

Dem gesamten Arbeitskreis Gladysz danke ich für das angenehme Arbeitsklima, sowie für

viele fachliche und außerfachliche Anregungen und Aktivitäten.

Insbesondere danke ich hierbei Sabine Seidel für die Gemeinschaft und fachliche

Diskussion über den Laboralltag hinaus. Dank auch an Inka Wolf durch deren Nachbarschaft am

Schreibtisch der Erforschung der Entropie keine Grenzen gesetzt waren. Auch Dirk Skaper hat den

Büro- und Laboralltag durch seine Anwesenheit stets aufgelockert. Dank schulde ich auch Dr.

Frank Hampel, der Unmögliches möglich machte.

Ganz besonderen Dank schulde ich meinen Eltern, Biene und meinen Freunden für die

moralische Unterstützung und den Beistand während dieser Doktorarbeit.

vii

Zusammenfassung

In dieser Dissertation wird die Entwicklung neuer rheniumhaltiger Phosphine beschrieben,

und deren Wirksamkeit als "Organokatalysatoren" bezüglich enantioselektiver Morita Baylis

Hillman und Rauhut Currier Reaktionen untersucht. Außerdem wird gezeigt, dass achirale fluorige

Phosphine sowohl wirksame als auch rückgewinnbare Katalysatoren für oben genannte Reaktionen

sind.

Kapitel 1 beschreibt kurz die historische Entwicklung der Morita Baylis Hillman und der

Rauhut Currier Reaktionen.

Kapitel 2 zeigt zuerst, dass bereits bekannte chirale rheniumhaltige Phosphine wirksame

Katalysatoren für die Morita Baylis Hillman und Rauhut Currier Reaktionen sind. Anschließend

werden neue rheniumhaltige Phosphine entwickelt und getestet, wobei die Reaktionen bezüglich

Geschwindigkeit und Enantioselektivität optimiert werden.

In C6H6 und PhCl katalysiert das racemische rheniumhaltige Phosphin (η5-

C5H5)Re(NO)(PPh3)(CH2PPh2) (1a; 10 mol%) eine intramolekulare Morita Baylis Hillman

Reaktion ausgehend von (E)-Ph(CO)CH=CHCH2CH2CHO (2a) zu Ph(CO)C=CHCH2CH2CHOH,

wobei Ausbeuten von 90% bis 95% nach 0.8-2.0 h bei Raumtemperatur erhalten werden.

Die ähnlichen Verbindungen (E)-R(CO)CH=CHCH2(CH2)nCHO (2; n/R = b, 1/EtO; c,

1/CH3O; d, 1/p-Tol; e, 1/CH3; f, 1/i-PrS; g, 2/p-Tol; h, 2/CH3; i, 2/EtO; j, 2/CH3O; k, 2/Ph) und

die Bis(enone) (E,E)-R(CO)CH=CHCH2(CH2)nCH=CH(CO)R (3; n/R = a, 1/Ph; b, 1/CH3; c, 1/i-

PrS; d, 2/CH3; e, 2/p-Tol) werden auf Zyklisierungen zu den Morita Baylis Hillman Produkten

R(CO)C=CHCH2(CH2)nCHOH und Rauhut Currier Produkten R(CO)C=CHCH2-

(CH2)nCHCH2(CO)R untersucht. Während einige Substrate (2a,d-h, 3a-c) mit 1a (10 mol%) gute

Reaktivitäten und Produktausbeuten (50-99%) aufweisen, werden andere Substrate (2b,c,i-k, 3d,e)

schlecht oder gar nicht umgesetzt.

Mehrere andere rheniumhaltige Phosphine mit der Formel (η5-C5H4R)Re(NO)(PPh3)-

(CR'HPR''R''') (4; R/R'/R''/R''' = a, H/CH3/Ph/Ph; b, H/Ph/Ph/Ph; c, PPh2/Ph/Ph/Ph; d,

viii

PPh2/H/Ph/Ph; e, H/H/Cy/Ph; f, H/H/Cy/t-Bu) werden synthetisiert, wobei 4a eine neue

Verbindung ist. Diese Phosphine werden als Katalysatoren für die Zyklisierungen von 2a,b,h,i,k

unter den selben Reaktionsbedingungen wie vorher getestet. Die Katalysatoren 4a-f sind weit

weniger reaktiv als 1a, trotzdem werden NMR-Ausbeuten von bis zu 90% erzielt.

Reaktionen von enantiomerenreinen (1a, 4d), diastereomerenreinen (4a) oder

diastereomerenangereicherten (4e) Katalysatoren werden mit verschiedenen Substraten

durchgeführt. Dabei werden mittels chiraler HPLC ee Werte von 3% bis 74% bestimmt. Die besten

Ergebnisse werden mit 1a erzielt (38-74% ee).

Die neuen rheniumhaltigen Phosphine (η5-C5H5)Re(NO)(PPh3)(CH2PRR') (1; R/R' = b, p-

Tol/p-Tol; c, p-C6H4OCH3/p-C6H4OCH3; d, p-C6H4N(CH3)2/p-C6H4N(CH3)2; e, 2-biphen/2-

biphen; f, α-naph/α-naph; g, Ph/α-naph; h, Ph/β-naph) werden auch enantiomerenrein (1b-d) und

diastereomerenangereichert (1g,h) synthetisiert (siehe unten). Bei Testreaktionen dieser als

Katalysatoren (10 mol%) mit verschiedenen Substraten werden im besten Fall quantitative

Produktausbeuten erzielt. Die detektierten Enantioselektivitäten variieren von –11% bis 88%, wobei

1g der selektivste Katalysator von allen ist (53-88% ee).

Kapitel 3 beschreibt die Synthese der neuen rheniumhaltigen Phosphine, welche in Kapitel 2

als Katalysatoren eingesetzt wurden. Diese werden ausgehend von dem bereits bekannten

Methylkomplex (η5-C5H5)Re(NO)(PPh3)(CH3) (5) synthetisiert. Für die Darstellung racemischer

Komplexe wird 5 mit Ph3C+ PF6– umgesetzt, wobei der Methylidenkomplex [(η5-

C5H5)Re(NO)(PPh3)(=CH2)]+ PF6– gebildet wird. Die darauffolgende Addition der sekundären

Phosphine PRR'H (6; R/R' = b, p-Tol/p-Tol; c, p-C6H4OCH3/p-C6H4OCH3; d, p-C6H4N(CH3)2/p-

C6H4N(CH3)2; e, 2-biphen/2-biphen; f, α-naph/α-naph) führt zu den Phosphoniumsalzen [(η5-

C5H5)Re(NO)(PPh3)(CH2PRR'H)]+ PF6– ([1(b-f)-H]+ PF6

–, 87-94%). Nach Deprotonierung mit t-

BuOK erhält man die reinen Phosphine 1b-f in guten Ausbeuten (64-91%). Analoge Umsetzungen,

welche allerdings mit (S)-5 durchgeführt werden, ergeben die enantiomerenreinen Phosphine (S)-

1b-d in vergleichbaren Ausbeuten. In einer ähnlichen Reaktionsabfolge werden die beiden

racemischen sekundären Phosphine PHRR' (6; R/R' = g, Ph/α-naph; h, Ph/β-naph) eingesetzt.

Ersteres führt mit 78% Ausbeute zu dem Phosphoniumsalz [1g-H]+ PF6–, welches aus einem

ix

Gemisch von SReRP/SReSP Diastereomeren besteht. Mittels mehrmaligen Ausfällens aus n-

Pentan/CH2Cl2 werden die SReRP und SReSP Diastereomere getrennt, wobei maximal 94% de

erhalten wird. Beide Diastereomere werden unter Retention der Phosphorkonfiguration deprotoniert

und der oben eingesetzte Katalysator 1g wird erhalten. Mit 6h wird auf ähnlichem Weg Komplex

(SReRP)/(SReSP)-1h (50:50) hergestellt. Ausfällen aus n-Pentan/C6H6 liefert die SReRP and SReSP

Diastereomere mit maximal 92% de.

Der C-stereogene, protonierte Katalysator (SReSC)-[4a-H]+ PF6– wird synthetisiert indem

der bekannte Ethylkomplex (S)-(η5-C5H5)Re(NO)(PPh3)(CH2CH3) mit Ph3C+ PF6– bei –78 °C

umgesetzt wird. Dabei wird der Ethylidenkomplex (sc)-[(η5-C5H5)Re(NO)(PPh3)(=CH2CH3)]+

PF6– gebildet, welcher anschließend mit PPh2H zum Produkt reagiert. Dieses wird mit 55%

Ausbeute erhalten und direkt vor der Katalysereaktion deprotoniert, ohne das freie Phosphin direkt

zu charakterisieren.

Die Synthesen der sekundären Phosphine 6c-h werden beschrieben. Von diesen

Verbindungen sind drei neu (6e,g,h), welche mittels Reduktion der entsprechenden

Diarylchlorphosphine mit LiAlH4 in 32% bis 70% Ausbeute synthetisiert werden.

Kapitel 4 zeigt den erstmaligen Einsatz von fluorigen Phosphinen als Katalysatoren für

Morita Baylis Hillman und Rauhut Currier Reaktionen. Zwei bereits bekannte fluorige Phosphine

P((CH2)3(CF2)n-1CF3)3 (7; a, n = 6; b, n = 8) werden dafür untersucht. Eine mögliche

Rückgewinnung mittels Ausfällen wird getestet. Die Löslichkeit jener Phosphine ist in CH3CN bei

Raumtemperatur eher gering, steigt bei höheren Temperaturen (ca. 50-60 °C) aber deutlich an.

Demzufolge wird 2a in CH3CN gelöst und 7a,b (10 mol%) zugegeben. Die bei 60-64 °C

stattfindende Reaktion wird im Fall von 7b mittels HPLC verfolgt. Nachdem die Reaktionen

beendet sind und die Lösungen abgekühlt werden, fallen 7a,b wieder aus und werden in je einem

neuen, identischen Zyklus wiederverwendet. Das Reaktionsprodukt wird aus der überstehenden

Lösung isoliert. Da die Rückgewinnung von 7a nur moderat funktioniert, wird im folgenden dem

weniger löslichen 7b mehr Bedeutung beigemessen. Der Reaktionsverlauf von 2a mit 7b (10 mol%)

wird über fünf Zyklen hinweg verfolgt. Produktausbeuten von 78% bis 85% werden erzielt, wobei

die Aktivität pro Zyklus kaum abnimmt.

x

Wenn gelöste fluorige Verbindungen abgekühlt werden, adsorbieren diese sehr leicht auf

fluorigen Feststoffen. In anderen Experimenten werden daher den Reaktionsmischungen fluorige

Polymere beigegeben (Teflon® Band und Gore-Rastex® Faser) um den Wiedergewinnungsprozess

effizienter zu gestalten. Je fünf Zyklen werden durchgeführt, wobei Ausbeuten von 66% bis 82%

(Teflon® Band) und 74% bis 82% (Gore-Rastex® Faser) erhalten werden. Allerdings wird ein

Aktivitätsverlust während des vierten und fünften Zyklus festgestellt (Teflon® Band > Gore-

Rastex® Faser). Der Einsatzbereich von 7b wird mit drei Substraten (2f,g, 3c) erweitert. Je drei

Zyklen werden mittels HPLC oder GC verfolgt. Alle Reaktionen werden mit 10 mol% 7b in

CH3CN bei 60-72 °C durchgeführt. Ausbeuten von 71% bis 96% werden erzielt, wobei für jeden

folgenden Zyklus nur geringe Aktivitätsverluste beobachtet werden.

Kapitel 5 beschreibt eine einfache und extrem flexible Synthese für die Substrate 2 und 3.

Ausgehend von leicht erhältlichen Molekülbausteinen wie α-Bromacetylbromid oder

Methylketonen werden die α-Bromcarbonyle R(CO)CH2Br (R = EtO, CH3O, i-PrS, p-Tol, Ph, CH3;

36-90%) synthetisiert. Diese reagieren mit PPh3 zu den Phosphoniumsalzen [R(CO)CH2PPh3]+ Br–

in 60% bis 92% Ausbeute. Anschließende Deprotonierungen mit wässriger NaOH führen zu den

stabilen Yliden R(CO)CHPPh3 in 52% bis 85% Ausbeute. Die Ylide reagieren nach Wittig mit den

Dialdehyden OHCCH2(CH2)nCHO (n = 1, 2) je nach Stöchiometrie entweder zu den Morita Baylis

Hillman Substraten (2; 34-75%) oder zu den Rauhut Currier Substraten (3; 40-82%).

xi

Abstract

In this thesis, new chiral rhenium-containing phosphines are developed, and their

effectiveness as "organocatalysts" for enantioselective Morita Baylis Hillman and Rauhut Currier

reactions are assayed. Achiral fluorous phosphines are also shown to be effective as well as

recyclable catalysts for these reactions.

Chapter 1 briefly describes the historical development of the Morita Baylis Hillman and

Rauhut Currier reactions.

Chapter 2 first establishes that previously reported chiral rhenium-containing phosphines are

effective catalysts for the Morita Baylis Hillman and Rauhut Currier reactions. New rhenium-

containing phosphines are then developed and screened, optimizing rates and product

enantioselectivities.

In C6H6 and PhCl, the racemic rhenium-containing phosphine (η5-C5H5)Re(NO)(PPh3)-

(CH2PPh2) (1a; 10 mol%) effects an intramolecular Morita Baylis Hillman cyclization of (E)-

Ph(CO)CH=CHCH2CH2CHO (2a) to Ph(CO)C=CHCH2CH2CHOH in 90% to 95% yields after

0.8-2.0 h at room temperature.

The related compounds (E)-R(CO)CH=CHCH2(CH2)nCHO (2; n/R = b, 1/EtO; c, 1/CH3O;

d, 1/p-Tol; e, 1/CH3; f, 1/i-PrS; g, 2/p-Tol; h, 2/CH3; i, 2/EtO; j, 2/CH3O; k, 2/Ph) and the

bis(enones) (E,E)-R(CO)CH=CHCH2(CH2)nCH=CH(CO)R (3; n/R = a, 1/Ph; b, 1/CH3; c, 1/i-PrS;

d, 2/CH3; e, 2/p-Tol), are screened with respect to the Morita Baylis Hillman products

R(CO)C=CHCH2(CH2)nCHOH and Rauhut Currier products R(CO)C=CHCH2(CH2)nCH-

CH2(CO)R. Several substrates (2a,d-h, 3a-c) exhibit good reactivity towards 1a (10 mol%) with

good product yields (50-99%), while others show little or no reactivity (2b,c,i-k, 3d,e).

Several other rhenium-containing phosphines of the formulae (η5-C5H4R)Re(NO)-

(PPh3)(CR'HPR''R''') (4; R/R'/R''/R''' = a, H/CH3/Ph/Ph; b, H/Ph/Ph/Ph; c, PPh2/Ph/Ph/Ph; d,

PPh2/H/Ph/Ph; e, H/H/Cy/Ph; f, H/H/Cy/t-Bu) are prepared, the first one (4a) of which is a new

xii

compound. These are screened as catalysts for the cyclization of 2a,b,h,i,k under analogous

conditions. Catalysts 4a-f are much less active than 1a, but with 4a,d,e NMR yields up to 90% are

obtained.

Reactions of enantiopure (1a, 4d) and diastereopure (4a) or diastereoenriched (4e) catalysts

with various substrates are conducted under analogous conditions. Chiral HPLC establishes ee

values ranging from 3% to 74%. The best results are obtained with 1a (38-74% ee).

The new rhenium-containing phosphines (η5-C5H5)Re(NO)(PPh3)(CH2PRR') (1; R/R' = b,

p-Tol/p-Tol; c, p-C6H4OCH3/p-C6H4OCH3; d, p-C6H4N(CH3)2/p-C6H4N(CH3)2; e, 2-biphen/2-

biphen; f, α-naph/α-naph; g, Ph/α-naph; h, Ph/β-naph) are prepared (below) in enantiopure (1b-d)

and diastereoenriched (1g,h) form. These are screened (10 mol%) with various substrates, and give

up to quantitative product yields. Enantioselectivities range from –11% to 88%, with 1g being most

effective (53-88% ee).

Chapter 3 describes the preparation of the new rhenium-containing phosphines used as

catalysts in Chapter 2. These are synthesized from the previously reported methyl complex (η5-

C5H5)Re(NO)(PPh3)(CH3) (5). For racemic complexes, 5 is treated with Ph3C+ PF6– to generate

the methylidene complex [(η5-C5H5)Re(NO)(PPh3)(=CH2)]+ PF6–. The subsequent addition of the

secondary phosphines PRR'H (6; R/R' = b, p-Tol/p-Tol; c, p-C6H4OCH3/p-C6H4OCH3; d, p-

C6H4N(CH3)2/p-C6H4N(CH3)2; e, 2-biphen/2-biphen; f, α-naph/α-naph) give the phosphonium

salts [(η5-C5H5)Re(NO)(PPh3)(CH2PRR'H)]+ PF6– ([1(b-f)-H]+ PF6

–, 87-94%). Deprotonations

with t-BuOK give the pure phosphines 1b-f in good yields (64-91%). Analogous procedures

starting with (S)-5 give the enantiopure phosphines (S)-1b-d in comparable overall yields. Identical

sequences are conducted using the racemic secondary phosphines PHRR' (6; R/R' = g, Ph/α-naph; h,

Ph/β-naph). The first gives the phosphonium salt [1g-H]+ PF6– in 78% total yield as a mixture of

SReRP/SReSP diastereomers. Precipitations from n-pentane/CH2Cl2 allow the SReRP and SReSP

diastereomers to be obtained in up to 94% de. Both undergo deprotonation with retention of

configuration at phosphorus to give the 1g employed for catalysis above. With 6h, (SReRP)/(SReSP)-

1h (50:50) is similarly obtained. Precipitations from n-pentane/C6H6 give the SReRP and SReSP

diastereomers in up to 92% de.

xiii

The C-stereogenic protonated catalyst (SReSC)-[4a-H]+ PF6– is obtained by the reaction of

the previously reported ethyl complex (S)-(η5-C5H5)Re(NO)(PPh3)(CH2CH3) with Ph3C+ PF6– at

–78 °C to generate the ethylidene complex (sc)-[(η5-C5H5)Re(NO)(PPh3)(=CH2CH3)]+ PF6–,

followed by the addition of PPh2H. This material is obtained in 55% yield and directly deprotonated

before catalysis without characterization of the free phosphine.

The syntheses of the secondary phosphines 6c-h are described. Three of them are new

(6e,g,h), and are obtained by the reduction of the corresponding diarylchlorophosphines with

LiAlH4 in 32% to 70% yields.

Chapter 4 describes the first use of fluorous phosphines as catalysts for Morita Baylis

Hillman and Rauhut Currier reactions. Two previously reported fluorous phosphines P((CH2)3-

(CF2)n-1CF3)3 (7; a, n = 6; b, n = 8) are tested for their suitability for recovery by precipitation.

They are only slightly soluble in CH3CN at room temperature, but become much more soluble at

elevated temperatures (ca. 50-60 °C). Therefore, CH3CN solutions of 2a are treated with 7a,b (10

mol%) at 60-64 °C and the reaction with 7b is monitored by HPLC. Upon completion and cooling,

7a,b precipitate and are reused in an identical cycle. The product is isolated from the supernatant.

The recovery with 7a is low, and therefore attention is focused on the less soluble 7b. The rate of

the reaction of 2a with 7b (10 mol%) is monitored for five cycles. Product yields range from 78%

to 85%, with only a slight loss of activity.

In parallel experiments, fluoropolymers (Teflon® tape and Gore-Rastex® fiber) are added to

mechanically facilitate the recycling process, as fluorous compounds easily adsorb onto such

polymers upon cooling. Five reaction cycles are accomplished using each recycling strategy, with

product yields ranging from 66% to 82% (Teflon® tape) and 74% to 82% (Gore-Rastex® fiber).

However, some loss of activity is seen in the fourth and fifth cycle (Teflon® tape > Gore-Rastex®

fiber). The scope of these protocols is broadened with three further substrates (2f,g, 3c). The rates of

three cycles, each with 10 mol% 7b in CH3CN at 60-72 °C, are monitored by HPLC or GC. The

yields range from 71% to 96%, with only a slight loss of activity.

Chapter 5 describes a simple and extremely versatile synthetic route to the substrates 2 and 3

xiv

employed in Chapters 2 and 4. Starting with readily accessible building blocks such as α-

bromoacetyl bromide or methyl ketones, α-bromocarbonyl derivatives R(CO)CH2Br (R = EtO,

CH3O, i-PrS, p-Tol, Ph, CH3; 36-90%) are prepared. These react with PPh3 to give the

phosphonium salts [R(CO)CH2PPh3]+ Br– in 60% to 92% yields. Subsequent deprotonations with

aqueous NaOH give the stable ylides R(CO)CHPPh3 in 52% to 85% yields. The ylides undergo

Wittig reactions with the dialdehydes OHCCH2(CH2)nCHO (n = 1, 2) to give either Morita Baylis

Hillman substrates (2; 34-75%) or Rauhut Currier substrates (3; 40-82%), depending on the

stoichiometry.

xv

Table of Contents

Zusammenfassung..............................................................................................................................vii

Abstract ...............................................................................................................................................xi

List of Schemes.................................................................................................................................xix

List of Figures ...................................................................................................................................xxi

List of Tables .................................................................................................................................xxvii

1 General Introduction ...................................................................................................................1

1.1 Organocatalysis – a New Chapter within Catalytic Chemistry............................................1

1.2 The Historical Rauhut Currier and Morita Baylis Hillman Reaction ..................................3

1.3 The Intramolecular Phosphine Catalyzed Rauhut Currier Reaction....................................5

1.4 The Intramolecular Phosphine Catalyzed Morita Baylis Hillman Reaction........................8

1.5 Future Directions................................................................................................................11

2 Enantioselective Organocatalysis with Rhenium-Containing Phosphines ...........................13

2.1 Introduction........................................................................................................................13

2.2 The Intramolecular Morita Baylis Hillman and Rauhut Currier Reaction:

First Experiments ...............................................................................................................19

2.2.1 Results ........................................................................................................................19

2.2.1.1 A First Reaction Series ......................................................................................... 19

2.2.1.2 Solvent Dependency ............................................................................................. 20

2.2.1.3 Temperature Dependency ..................................................................................... 21

2.2.1.4 Substrate Dependency........................................................................................... 23

2.2.1.5 Reactions with Other Rhenium-Containing Phosphines....................................... 26

2.2.1.6 Enantioselective Catalyses.................................................................................... 29

2.2.2 Discussion ..................................................................................................................31

2.2.2.1 Solvent Dependency ............................................................................................. 31

2.2.2.2 Temperature Dependency ..................................................................................... 33

2.2.2.3 Substrate Dependency........................................................................................... 33

xvi

2.2.2.4 Formation of a Side Product ................................................................................. 34

2.2.2.5 Oxidation of the Catalyst ...................................................................................... 35


2.2.2.7 Activity of Different Phosphorus Centers............................................................. 39

2.2.2.8 Conclusions ..........................................................................................................41

2.3 First Series of Improved Catalysts .....................................................................................42

2.3.1 Results ........................................................................................................................42

2.3.1.1 Increased Nucleophilicity by Electron Rich Aryl Substituents ............................ 42


2.3.1.3 Preparative Experiments ....................................................................................... 47

2.3.2 Discussion ..................................................................................................................49

2.4 Second Series of Improved Catalysts.................................................................................51

2.4.1 Results ........................................................................................................................51

2.4.1.1 Increased Steric Demand at the Catalytic Center.................................................. 51

2.4.1.2 Introduction of Chirality at the Catalytic Center .................................................. 53


2.4.2 Discussion ..................................................................................................................57

2.4.2.1 Discussion of the Second Series Improved Catalysts ........................................... 57

2.4.2.2 Short Summary and Outlook................................................................................. 58

2.5 Experimental ......................................................................................................................60

2.5.1 General Data...............................................................................................................60

2.5.2 General Procedures.....................................................................................................61

2.5.3 Analytic Experiments Listed by Figures ....................................................................63

2.5.4 Preparative Reactions .................................................................................................74

2.5.5 Isolation of Side Product C=CHCH2CH2CHCH2C(CH3)(OH)CH2(CO) (19) .........76

3 Rhenium-Containing Phosphines .............................................................................................77

3.1 Introduction to Rhenium Complexes .................................................................................77

3.2 Results................................................................................................................................81

xvii

3.2.1 Preparation of Rhenium Complexes...........................................................................81

3.2.1.1 Preparation of Racemic Rhenium-Containing Phosphines................................... 81

3.2.1.2 Preparation of Enantiopure Complexes ................................................................ 85

3.2.1.3 Preparation of Diastereomeric Mixtures of P Chiral Complexes ......................... 86

3.2.1.4 Preparation of (SReSC)-[(η5-C5H5)Re(NO)(PPh3)(CHCH3PPh2H)]+ PF6–

((SReSC)-[15b-H]+ PF6–) ....................................................................................... 91

3.2.2 Preparation of Secondary Phosphines ........................................................................92

3.2.2.1 Preparation via Reduction of Secondary Phosphine Oxides................................. 93

3.2.2.2 Preparation via Reduction of Diarylchlorophosphines ......................................... 93

3.3 Discussion ..........................................................................................................................95

3.4 Experimental ......................................................................................................................97

3.4.1 General Data...............................................................................................................97

3.4.2 Preparation of Rhenium-Containing Phosphines .......................................................98

3.4.3 Preparation of Secondary Phosphines ......................................................................113

4 Recycling of Fluorous Phosphines from Organocatalytic Reactions ..................................117

4.1 Introduction......................................................................................................................117

4.1.1 Introduction of Fluorous Concepts and Recycling...................................................117

4.1.2 Introduction of Fluorous Phosphines .......................................................................123

4.2 Results..............................................................................................................................126

4.2.1 Catalytic Reactions with P((CH2)3Rf6)3 (30a) ........................................................126

4.2.2 Catalytic Reactions with P((CH2)3Rf8)3 (30b) ........................................................129

4.2.2.1 Reactions with Substrate C1Ph........................................................................... 129

4.2.2.2 Reactions with Substrates C1S(i-Pr) and C1S(i-Pr)2......................................... 131

4.2.2.3 Reactions with Substrate C2(p-Tol) ................................................................... 133

4.2.2.4 Preparative Experiments ..................................................................................... 134

4.2.3 Recycling of 30b by Precipitation............................................................................135

4.2.3.1 Recycling from Reactions with C1Ph................................................................. 135

4.2.3.2 Recycling from Reactions with C1S(i-Pr), C1S(i-Pr)2, and C2(p-Tol)............. 137

xviii

4.2.4 Recycling of 30b with Fluoropolymer Supports......................................................140

4.2.4.1 Recycling with the Support of Teflon® Tape..................................................... 141

4.2.4.2 Recycling with the Support of Gore-Rastex® Fiber........................................... 143

4.2.5 Thermomorphic Behavior of 30b in CH3CN...........................................................145

4.3 Discussion ........................................................................................................................147

4.4 Experimental ....................................................................................................................149

4.4.1 General Data.............................................................................................................149

4.4.2 Analytic Experiments Listed by Figures or Tables ..................................................149

4.4.2.1 Experiments with Catalyst 30a ........................................................................... 149

4.4.2.2 Experiments with Catalyst 30b ........................................................................... 150

4.4.3 Preparative Reactions ...............................................................................................155

4.4.4 Thermomorphic Behavior of 30b.............................................................................156

5 Preparation of Substrates........................................................................................................157

5.1 Introduction......................................................................................................................157

5.2 Results..............................................................................................................................160

5.2.1 Preparation of the Stable Ylides...............................................................................160

5.2.2 Wittig Reactions of the Stable Ylides with Dialdehydes .........................................162

5.3 Discussion ........................................................................................................................164

5.4 Experimental ....................................................................................................................166

5.4.1 General Data.............................................................................................................166

5.4.2 Ylide Preparation......................................................................................................166

5.4.3 Substrate Preparation................................................................................................171

5.4.3.1 Morita Baylis Hillman Substrates ....................................................................... 171

5.4.3.2 Rauhut Currier Substrates ................................................................................... 173

6 References and Notes ...............................................................................................................177

xix

List of Schemes

Scheme 1.1. Dimerization of an alkyl acrylate (I), mediated by tertiary phosphines; the

"historical" Rauhut Currier reaction.

Scheme 1.2. Addition of PPh3 to acrylonitrile gives a zwitterionic species III which yields to the

ylide IV.

Scheme 1.3. Wittig reaction of ylide IV with aromatic aldehydes.

Scheme 1.4. Reaction sequence published by Morita. The double bond is activated by an electron

withdrawing group (EWG). The moiety R can be aliphatic as well as aromatic.

Scheme 1.5. Reaction cycle for the phosphine catalyzed intramolecular Rauhut Currier reaction.

Scheme 1.6. Intramolecular Rauhut Currier reaction published by Krische.

Scheme 1.7. The Rauhut Currier reaction as a key step for the total synthesis of (–)-spinosyn A

reported by Roush.

Scheme 1.8. Reaction cycle for the phosphine catalyzed intramolecular Morita Baylis Hillman

reaction.

Scheme 1.9. First intramolecular Morita Baylis Hillman reaction carried out by Fráter.

Scheme 1.10. Representative reaction reported by Murphy.

Scheme 2.1. Enhanced basicity of the lone pairs of (η5-C5H5)Re(NO)(PPh3)(CH2SCH3) (1).

Scheme 2.2. First intramolecular Morita Baylis Hillman reactions with C1Ph and 10 mol% of 14a,

carried out in different solvents.

Scheme 2.3. Formation of cyclic side products 19 and 20 from the reaction of C1Me2 with 10

mol% 14b in PhCl.

Scheme 2.4. Possible pathway for the formation of catalyst-derived phosphorus oxide.

Scheme 2.5. Possible future directions for catalysts based upon rhenium-containing phosphines.

Scheme 3.1. Syntheses of rhenium-containing phosphines with chiral centers. Enantioselective

(and diastereoselective) syntheses are possible in each case. a) Ph3C+ PF6–, CH2Cl2.

b) PPh2H. c) t-BuOK, THF. d) n-BuLi, THF. e) PPh2Cl. f) PhLi. g) t-BuLi. h)

HBF4.OEt2, PhCl.

xx

Scheme 3.2. Preparation of the protonated racemic rhenium-containing phosphines [14-H]+ PF6–.

a) Ph3C+ PF6– (1.1 equiv.), CH2Cl2. b) PR2H.

Scheme 3.3. Deprotonation of the racemic phosphonium salts [14-H]+ PF6–. a) t-BuOK (1.5

equiv.), C6H6.

Scheme 3.4. Preparation of the protonated diastereomeric rhenium-containing phosphines

(SReRP)/(SReSP)-[17-H]+ PF6–. a) Ph3C+ PF6

–, CH2Cl2. b) PRR'H.

Scheme 3.5. Preparation of (SReSC)-[15b-H]+ PF6–. a) Ph3C+ PF6

–, CH2Cl2, –78 °C. b) PPh2H.

Scheme 3.6. Syntheses of the secondary phosphines 28c,d (yields overall). a) Mg, THF. b)

OP(OEt)2H. c) DIBAL-H. d) NaOH/H2O.

Scheme 3.7. Synthesis of the secondary phosphines 28e,f. a) Mg, THF. b) PCl3. c) LiAlH4. d)

NaOH/H2O.

Scheme 3.8. Synthesis of the racemic secondary phosphines 29c,d. a) Mg, THF. b) PPhCl2. c)

LiAlH4. d) NaOH/H2O.

Scheme 4.1. General procedure for the syntheses of tertiary fluorous phosphines 30a,b.

Scheme 4.2. Intramolecular Morita Baylis Hillman reaction of C1Ph catalyzed by 10 mol% of

fluorous phosphine 30a.

Scheme 4.3. Cyclizations of substrates C1S(i-Pr) and C1S(i-Pr)2 catalyzed by 10 mol% of 30b.

Scheme 4.4. Cyclization of substrate C2(p-Tol) catalyzed by 10 mol% of 30b.

Scheme 4.5. Reaction sequence with recyclable catalyst system, reported by Yi.

Scheme 5.1. General route to substrates C1R, published by Koo.

Scheme 5.2. General route to substrates C1R, published by Denmark.

Scheme 5.3. General route to substrates C1R, published by Murphy.

Scheme 5.4. Preparation of the stable ylides 34.

Scheme 5.5. Preparation of the substrates CnR and CnR2, by reaction of ylides and dialdehydes.

xxi

List of Figures

Figure 1.1. Count of publications by year containing the topic "organocatalysis". Result from

SciFinder® search (07.2008).

Figure 1.2. Key features of the highly functionalized intramolecular Morita Baylis Hillman

product XVII.

Figure 2.1. General idealized structures of the rhenium fragment [(η5-C5H5)Re(NO)(PPh3)]+ (A)

and (η5-C5H5)Re(NO)(PPh3)(X) (B), upon which many rhenium complexes are

based.

Figure 2.2. Key orbital interactions in coordinatively saturated octahedral LnMPR2 (C) and

LnMCH2PR2 (D, E) complexes.

Figure 2.3. Rhenium-containing monophosphines that have been employed successfully in

catalysis.

Figure 2.4. Adducts of rhenium-containing diphosphines that have been employed successfully

in catalysis.

Figure 2.5. Reaction profiles for the formation of C1Phprod in Scheme 2.2 in different solvents.

The purple graph (♦) shows for comparison the reaction of C1Ph with 10 mol% of

PPh3 in CH2ClCH2Cl.

Figure 2.6. Reaction profiles for Scheme 2.2 at room temperature and 0 °C in CH3CN. The

former experiment is also in Figure 2.5.

Figure 2.7. Reaction profiles for Scheme 2.2 at room temperature and 40 °C in CH2ClCH2Cl.

The former experiment is also in Figure 2.5.

Figure 2.8. Substrates employed herein for catalytic reactions, and product structures. Substrates

with n = 1 (C1R, C1R2) give products with five-membered rings (C1Rprod,

C1R2prod) and with n = 2 (C2R, C2R2) give products with six-membered rings

(C2Rprod, C2R2prod). Many have already been reported in the literature: C1Ph,

25,28,42,43 C2Me,44 C1Ph2,19,20,26,45 C1OEt,25 C1OMe,46-48 C2OEt,25,46,49

C2OMe,47,48 C2Ph, 25 C1Me,28 C1(p-Tol),42,43 C2Me2,26 and C1Me250).

Figure 2.9. Reaction profiles for the cyclizations of various substrates under the conditions of

xxii

Scheme 2.2 in PhCl; the data for C1Ph are repeated from Figure 2.5.


Scheme 2.2 in PhCl and C6H6; the data for C1Ph involving PhCl are repeated from

Figure 2.5.

Figure 2.11. Rhenium-containing phosphines that were screened as catalysts.

Figure 2.12. Reaction profile for the cyclization of C1Ph with 10 mol% of (SReSC)-15b in PhCl.

Figure 2.13. Reaction profile for the cyclization of C1Ph with 10 mol% of (S)-16b in PhCl.

Figure 2.14. Reaction profiles for the cyclizations of C1Ph (■) and C2Me (∆) with 10 mol% of

(SReSP)/(SReRP)-17a in PhCl.

Figure 2.15. Top rated solvents for the intramolecular Morita Baylis Hillman reactions described

herein and their dielectric constants.

Figure 2.16. Possible substrate-catalyst interaction that may be a factor in solvent rate trends.

Figure 2.17. 1H NMR spectrum of side products obtained from the reaction of C1Ph with 10

mol% 14a at –25 °C in PhCl.

Figure 2.18. Newman projections down the Ph2P-CHR[Re] bonds of catalysts 14a and 15.

Figure 2.19. Qualitative comparison of different types of phosphorus donor groups with respect to

reactivity towards C1Ph.

Figure 2.20. Newman like projection down the η5-C5H4PPh2-Re axis of (S)-16b.

Figure 2.21. New rhenium-containing phosphines 14b-d.

Figure 2.22. Reaction profiles for the cyclizations of various substrates with 10 mol% of 14a-c in

C6H6; the data for C1S(i-Pr) and C2(p-Tol) involving 14a are repeated from Figure

2.10.

Figure 2.23. Reaction profiles for the cyclization of C2(p-Tol) with 10 mol% 14a-c in C6H6.

Conversion refers to the consumption of substrate. The product yield data are

repeated from Figure 2.22.

Figure 2.24. New rhenium-containing phosphines 14e,f.

Figure 2.25. Reaction profiles for the cyclizations of C1Ph (■) and C1S(i-Pr) (▲) with 10 mol%

14f in C6H6. The conversion of 14f to other species in the former reaction is given by

the orange trace (*).

xxiii

Figure 2.26. New rhenium-containing P-stereogenic phosphines (SReSP)/(SReRP)-17c,d.


of (SReSP)/(SReRP)-17c in C6H6.


of (SReSP)/(SReRP)-17d in C6H6.

Figure 3.1. Enantiopure complexes (S)-14b-d, obtained from (S)-(η5-C5H5)Re(NO)(PPh3)(CH3)

((S)-26) by procedures analogous to the racemates (Schemes 3.2 and 3.3).

Figure 3.2. Partial 1H NMR spectrum (CD2Cl2) of an aliquot of the reaction mixture that yields

(SReSP)/(SReRP)-[17c-H]+ PF6– (δ in ppm).

Figure 3.3. Partial 1H NMR spectra (CD3CN) of diastereomeric mixtures of (SReSP)/(SReRP)-

[17c-H]+ PF6– (δ in ppm), de = 92% and –92%.

Figure 4.1. Common orthogonal liquid phases.

Figure 4.2. Concept A: Recycling of a fluorous catalyst from biphasic liquid/liquid systems. I:

lower temperature, biphasic system, catalyst dissolved in phase B, substrate

dissolved in phase A. II: higher temperature, monophasic system, catalyst and

substrate dissolved in the mixed phase AB. III: lower temperature, biphasic system,

catalyst dissolved in phase B, product dissolved in phase A.

Figure 4.3. Concept B: Recycling of a fluorous catalyst from biphasic solid/liquid systems. I:

lower temperature, biphasic system, undissolved solid catalyst, substrate dissolved in

phase A. II: higher temperature, monophasic system, catalyst and substrate dissolved

in phase A. III: lower temperature, biphasic system, solid undissolved catalyst,

product dissolved in phase A.

Figure 4.4. Concept C: Recycling of a fluorous catalyst from biphasic solid/liquid systems with

fluoropolymer support. I: lower temperature, biphasic system, undissolved solid

catalyst which is coated on a fluoropolymer, substrate dissolved in phase A. II:

higher temperature, monophasic system, catalyst and substrate dissolved in phase A,

uncoated solid fluoropolymer. III: lower temperature, biphasic system, undissolved

solid catalyst which is again coated on the fluoropolymer, product dissolved in phase

A.

xxiv

Figure 4.5. General structure for the phosphines P((CH2)3Rfn)3 (30, a: n = 6, b: n = 8) that were

employed for the intramolecular Morita Baylis Hillman and related reactions.

Segment A: catalytically active center. Segment B: methylene spacers for modulation

of electronic and solubility properties. Segment C: fluorous tag, also for modulation

of solubility properties.

Figure 4.6. Reactions of C1Ph with 10 mol% of 30b in CH3CN at 60-64 °C. Aliquots of one

were assayed by 1H NMR (■), and the other (smaller scale) by HPLC (▲).

Figure 4.7. Reactions of C1S(i-Pr) with 10 mol% of 30b in CH3CN at 60-64 °C. Aliquots of one

were assayed by 1H NMR (■), and the other (smaller scale) by GC (▲).

Figure 4.8. Reactions of C1S(i-Pr)2 with 10 mol% of 30b in CH3CN at 60-64 °C. Aliquots of

one were assayed by 1H NMR (■), and the other (smaller scale) by GC (▲).

Figure 4.9. Reaction of C2(p-Tol) with 10 mol% of 30b in CH3CN at 70-72 °C. Aliquots were

assayed by HPLC.

Figure 4.10. A: Reaction mixture prior to heating. B: Reaction mixture after cooling. C: Catalyst

after separation from the reaction mixture. D: Recovered catalyst.

Figure 4.11. Reaction of C1Ph with 10 mol% of 30b in CH3CN at 60-64 °C. Aliquots were

assayed by HPLC.

Figure 4.12. Reaction of C1S(i-Pr) with 10 mol% of 30b in CH3CN at 60-64 °C. Aliquots were

assayed by GC.

Figure 4.13. Reaction of C1S(i-Pr)2 with 10 mol% of 30b in CH3CN at 60-64 °C. Aliquots were

assayed by GC.


assayed by HPLC.

Figure 4.15. Photographs from cycle 1 of Figure 4.16. A: Reaction mixture prior to heating. B:

Reaction mixture after cooling to –30 °C. C: Washed and dried Teflon® tape, coated

with catalyst.

Figure 4.16. Reaction of C1Ph with 10 mol% of 30b in CH3CN at 60-64 °C in the presence of

Teflon® tape. Aliquots were assayed by HPLC.


xxv

Reaction mixture after cooling. C: Washed and dried Gore-Rastex® fiber, coated

with catalyst.


Gore-Rastex® fiber. Aliquots were assayed by HPLC.

Figure 4.19. Solubility of 30b in CH3CN as a function of temperature. The hysteresis curve was

determined from two independent 19F NMR experiments. Red (■): heating curve.

Blue (▲): cooling curve.

xxvii

List of Tables

Table 2.1. Product ee values for reactions of C1Ph with 10 mol% of enantiopure catalysts in

PhCl.

Table 2.2. Product ee values for reactions of various substrates with 10 mol% of (S)-14a in

C6H6 and PhCl.

Table 2.3. Product yields for reactions of various substrates with 10 mol% 14a-d in PhCl.

Table 2.4. Product ee values for reactions of various substrates with 10 mol% (S)-14a-c in C6H6.

The values for 14a are repeated from Table 2.2.

Table 2.5. Preparative and 1H NMR product yields for reactions of various substrates with 10

mol% of 14a in C6H6.


mol% of 14c in PhCl.

Table 2.7. Nucleophilicity factors (N) depending on para substituents (R) of aryl phosphines

reported by Mayr.

Table 2.8. Product ee values for reactions of C1Ph and C1S(i-Pr) with 10 mol% of catalysts

(SReSP)/(SReRP)-17c and (SReSP)/(SReRP)-17d in C6H6.

Table 3.1. 31P{1H} NMR shifts and coupling constants for the rhenium-containing phosphines

14a-f.

Table 3.2. Oxidation of 14b with time, assayed as described in the text.a

Table 3.3. Comparison of selected physical properties of diastereomers 1 and 2 of

(SReSP)/(SReRP)-[17c-H]+ PF6–.

Table 4.1. Qualitative solubility of 0.050 g 30a in several solvents at different temperatures.

Table 4.2. Reaction of C1Ph with 10 mol% of 30a in CH3CN at 60-64 °C for 2.5 h. Product

yield as a function of cycle (Concept B).

Table 4.3. Reaction of C1Ph with 10 mol% of 30a in CH3CN at 60-64 °C for 6 h. Product yield

as a function of cycle. Catalyst was recovered by precipitation (Concept B) or

adsorption onto Teflon® shavings (Concept C).

xxviii

Table 4.4. Reaction of C1Ph with 10 mol% of 30b in CH3CN at 60-64 °C for ca. 6 h. Yield as a

function of cycle (Concept B).

Table 4.5. Phosphine oxide O=30b formed during the reactions in Figure 4.12-4.14, as assayed

by 1H NMR and 31P{1H} NMR spectra. The result after the first cycle is from an

independent reaction.

Table 4.6. Phosphine oxide O=30b formed during the reactions in Figures 4.11, 4.16, and 4.18

as assayed by 1H NMR and 31P{1H} NMR spectra.

Table 5.1. Yields of substrates obtained from the reactions of succinaldehyde with ylides 34

(Scheme 5.5).

Table 5.2. Yields of substrates obtained from the reactions of glutaraldehyde with ylides 34

(Scheme 5.5).

1

General Introduction

1.1 Organocatalysis – a New Chapter within Catalytic Chemistry

Starting from the beginning of the organic chemistry, it has always been a challenge to

synthesize new compounds. Essential for this is the formation and breaking of atom-atom bonds.

For such transformations catalysts are often involved, achieving in many cases mild and economic

conditions. And very often products are accessible more easily, or even exclusively by catalytic

controlled reactions. A good case in point would be the formation of scalemic or even enantiopure

products. In the decades before the year 2000 mostly two categories of enantioselective catalysts

were recognized in reviews and course curricula. One was the enzyme catalyzed category and the

other the transition metal mediated one. Without doubt both are very important up to now and many

research groups concentrate on these areas.

However, the targets of interest naturally spread and the means for accomplishing catalysis

broadens. Therefore, in the last years the field of organocatalysis has become more and more

important. According to a recent review, organocatalysis is described as the acceleration of

chemical reactions through the addition of a substoichiometric quantity of an organic compound -

the organocatalyst.1 A simple SciFinder® search for the term "organocatalysis" shows the growing

interest for this field (Figure 1.1).

As depicted, starting with the year 2000 and four publications it can be estimated that during

the calendar year 2008 over 900 publications will be released. This does not necessarily show that

this field was unknown before; of course it was not, only the term "organocatalysis" was coined by

MacMillan in 2000.2 One of the earliest reports wherein a reaction was enantioselectively catalyzed

by organic molecules, in this special case by cinchona alkaloids, was that from Pracejus in 1960.3,4

2 1 General Introduction

Figure 1.1. Count of publications by year containing the topic "organocatalysis". Result from

SciFinder® search (07.2008).

However, the increasing number of publications in the last decade reflects the great interest

within the chemistry community, as there is clearly a high potential for future applications. As the

field has spread widely and there is a plethora of reactions involving organocatalysis, a full

overview is not attempted within this introduction. There are several excellent reviews available,

which illustrate the incredible breadth of this subject.1,5-10 For this reason only reactions relevant to

this thesis are highlighted within this introduction.

For many reactions, organocatalysts offer several notable advantages: usually they are small

organic molecules that are cheap, inert towards oxygen and moisture, and often available on large

scales from the "chiral pool". However, the enantiopure catalysts that are obtained from the "chiral

pool" are commonly only available as one stereoisomer. The other stereoisomer is often not

available or only accessible via an extended synthetic pathway. Furthermore, there are some

reactions that can, in comparison to other familiar transformations, only be quite slowly catalyzed.

Examples extensively studied within this thesis include the Morita Baylis Hillman reaction and the

related Rauhut Currier reaction. The latter is often referred to the vinylogous Morita Baylis Hillman

reaction. In this thesis it was of primary interest to design organocatalysts for the Baylis Hillman

and the Rauhut Currier reaction offering both high reactivities and enantioselectivities.

Independently from this the recycling capabilities of selected catalysts were investigated.

2000 2001 2002 2003 2004 2005 2006 2007 2008 0

100 200 300 400 500 600 700

Num

ber o

f pub

licat

ions

Year

1 General Introduction 3

1.2 The Historical Rauhut Currier and Morita Baylis Hillman Reaction

The Rauhut Currier reaction dates back to 1963, when Rauhut and Currier filed a US patent

on the reaction of alkyl acrylates (I) to yield the needed esters of 2-methylene glutaric acid (II),

mediated by tertiary phosphines (Scheme 1.1).11 This work was carried out at the American

Cyanamid Corporation, and was not further described in refereed journals.

Scheme 1.1. Dimerization of an alkyl acrylate (I), mediated by tertiary phosphines; the "historical"

Rauhut Currier reaction.

Rauhut and Currier described this reaction with several acrylates I, having moieties R with

one to twelve carbon atoms. Furthermore, they used several catalysts PR'3 having moieties R'

ranging from alkyl and alkenyl to alkoxy and others. They claimed that catalyst loads of 0.008-20

mol% are suitable for such reactions, depending on the educt. Independently from this, McClure12

and Baizer13 described similar phosphine mediated reactions with acrylonitriles.

In the year 1962, Price reported the initial reaction of PPh3 with acrylonitrile in the course

of investigating polymerization reactions. He postulated a kind of tautomerism leading from the

Michael adduct III to the ylide IV (Scheme 1.2).14

Scheme 1.2. Addition of PPh3 to acrylonitrile gives a zwitterionic species III which yields to the

ylide IV.

OR

O

PR'3 RO

O

OR

O

I II

2

CNPPh3 CNPh3P

CNPh3P

III IV


In earlier studies, he had employed the zwitterion III to initiate polymerization of the

acrylonitrile. However, he found that in the presence of protolytic solvents like EtOH, a proton of

zwitterion III migrated to give ylide IV. The latter was noted to be thermodynamically more stable.

Two years later, in 1964, Tanimoto thought about the utilization of ylides like IV to effect

Wittig reactions.15 He was able to successfully implement this idea, leading to the olefination

products V. He demonstrated these reactions for the case of PPh3 with several acrylonitrile

derivatives and aldehydes. An example involving ylide IV is depicted in Scheme 1.3.

Scheme 1.3. Wittig reaction of ylide IV with aromatic aldehydes.

Of course, for this kind of reaction a stoichiometric amount of PPh3 is needed and after the

reaction is finished the whole amount of phosphine is oxidized. Therefore, this reaction is not

catalytic. Also only moderate yields were realized (< 56%).

Morita, from the Toyo Rayon Company, knew about the isomerization from zwitterionic

structure III to ylide IV and did similar experiments but with acrylonitriles and acrylates VI. Also,

he added an aldehyde to the mixture to get coupling products. He could successfully intercept III

with the aldehyde, using catalytic amounts of the aliphatic phosphine PCy3 (Scheme 1.4).16

Scheme 1.4. Reaction sequence published by Morita. The double bond is activated by an electron

withdrawing group (EWG). The moiety R can be aliphatic as well as aromatic.

He never observed products that were derived from isomer IV, and he attributed this to the

OPPh3CNPh3P

IV

(Aryl)CHO CN

VAryl

RCHO H2C C

EWG

CH(OH)RVI VII

PCy3H2C C

EWG

H

0.6 mol%


use of trialkylphosphine PCy3 catalyst. In contrast Price (Scheme 1.2), as well as Tanimoto

(Scheme 1.3), employed the aromatic tertiary phosphine PPh3. However, the selectivities and

conversions they published for a special sample were very low (both ca. 20%).

Several years later, in 1972, Baylis and Hillman from the Celanese Corporation announced a

patent dealing with the same reaction that Morita had found, but with a distinctly improved

procedure.17 Therein they complained about Morita's poor yields, the deactivation of the phosphine

catalyst, and the high amount of side products. To avoid such problems, they employed tertiary

amines that had at least one bridgehead nitrogen atom, for example DABCO. Such strongly basic

catalysts could act as nucleophiles and were inert towards oxidation. In contrast to the preceding

reactions, Baylis and Hillman's normally proceeded at room temperature and only small amounts of

side products were obtained.

However, after the patent of Baylis and Hillman was accredited, for many years no

publications about this kind of reaction were released. Perhaps the patent discouraged many

research groups from investigating this reaction in more detail. Around the year 1990 several

publications were released as a simple SciFinder® search showed. Around 2000 more and more

groups focused onto this organocatalytic reaction and in 2007 more and more publications (231)

appeared. Also, many variants of this reaction have now been established. The next sections will

focus on phosphine catalyzed, intramolecular reactions.

1.3 The Intramolecular Phosphine Catalyzed Rauhut Currier Reaction

Little attention was paid to the Rauhut Currier reaction for many years. Conceivably there

were problems concerning the reactivity and particularly the chemoselectivities for the

intermolecular variant.18 However, an intramolecular variant locates the subsequently reacting

electrophile within the same molecule. The reaction cycle for the intramolecular variant is shown in

Scheme 1.5.

The reaction starts with substrate VIII. This contains two potentially equivalent double

bonds, each activated by an electron withdrawing group (EWG). One of these Michael systems then

undergoes nucleophilic attacked by a tertiary phosphine resulting in the zwitterionic intermediate


IX, wherein the carbanion is stabilized by the EWG'. This step is mostly reported to be an

equilibrium. Subsequently, the carbanion attacks the second intramolecular Michael system giving

the cyclic, zwitterionic intermediate X, which is also stabilized, but this time by the second EWG''.

Proton transfer gives intermediate XI, which subsequently undergoes an E1-cb type elimination.

This provides product XII while releasing the phosphine catalyst for the next reaction cycle. As

denoted within the cycle several stereocenters (*) are formed. However, two of them are removed

en route from X to XII due to the phosphine elimination. Nonetheless, the product still contains one

chiral center.

Scheme 1.5. Reaction cycle for the phosphine catalyzed intramolecular Rauhut Currier reaction.

In 2001 Krische published a communication wherein he reported a phosphine catalyzed

intramolecular variant of the Rauhut Currier reaction.19 He investigated the chemoselectivities with

educts that featured two independent Michael systems. These systems were connected by a two or

three carbon metyhlene spacer (VIII, n = 1, 2). An example with a two carbon atom spacer is

*EWG'

EWG''

PR3

EWG''

EWG'

n

*

EWG''

EWG'

nR3P

*

*

*EWG'

EWG''

R3Pn

n

VIII

IXX

XII

*

*

*EWG'

EWG''

R3Pn

XI


illustrated in Scheme 1.6.

Scheme 1.6. Intramolecular Rauhut Currier reaction published by Krische.

As depicted above two different products XII can be obtained, as the catalyst is presented

with independent Michael systems where it can attack. It was shown that very high selectivities

could be realized (> 95:5), depending on the Michael systems' substituents and the spacer chain

length. Also the reported product yields were very good (87%). Employing the same catalyst,

Murphy reported similar results in 2002.20

Roush reported in 2004 the total synthesis of (–)-spinosyn A, wherein one of the key steps

was the formation of a five-membered cyclic alkene (Scheme 1.7).21 This was achieved by an

intramolecular Rauhut Currier reaction that was promoted by eight equiv. of the tertiary phosphine

P(CH3)3. Although this is not a catalytic quantity, in this special case it was more important to

maximize the yields. And in fact, quantitative conversion to the desired product was reported.

Although it does not qualify as a phosphine catalyzed reaction, some attention should be

paid to a cysteine catalyzed variant published by Miller last year (2007).22 Therein he reports

intramolecular Rauhut Currier reactions mediated by thiolates with moderate to good yields. More

important are the excellent enantiomeric excess values (ee; up to 95%) he obtained under optimized

conditions. However, one equiv. of cysteine was required for optimum yields and


O

OEt

O

O O

OEt

OEt

O

O

PBu3

VIII, n = 1

EWG' = CH3(CO)

EWG'' = (CO)OEt

> 95:587%

XII, n = 1

EWG' = CH3(CO)

EWG'' = (CO)OEt

XII, n = 1

EWG' = (CO)OEt

EWG'' = CH3(CO)

10 mol%


Scheme 1.7. The Rauhut Currier reaction as a key step for the total synthesis of (–)-spinosyn A

reported by Roush.

1.4 The Intramolecular Phosphine Catalyzed Morita Baylis Hillman Reaction

The Morita Baylis Hillman reaction is closely related to the Rauhut Currier reaction. The

reaction cycle for the intramolecular phosphine catalyzed variant is shown in Scheme 1.8.

The cycle depicted below is very similar to that in Scheme 1.5. The difference is that the

carbanion of the zwitterionic intermediate XIV attacks the aldehyde (or ketone) group, which leads

to the zwitterionic alcoholate XV. A subsequent proton shift to give zwitterion XVI, followed by

elimination of the catalyst leads to the highly functionalized product XVII. Again several

stereocenters (*) are formed during the reaction cycle, and one remains in the chiral alcohol product

XVII.

Several phosphine catalyzed intramolecular Morita Baylis Hillman reactions have been

H H

O

OOCH3

OCH3OCH3

O

O

O

O

ON(CH3)2

R'''

R''H

O

OR'

R

OR'''

R''H

O

OR'

R

OP(CH3)3

(−)-spinosyn A

key step

8 equiv.


reported to date. The first was published in 1992 by Fráter who needed the particular product XIX

shown in Scheme 1.9.23 For his ring closing process the depicted substrate XVIII was found to be

most reactive with catalyst PBu3. However, the selectivity was only 75% and the reaction took 24 h

to finish. Amine catalysts did not afford any product XIX.

Scheme 1.8. Reaction cycle for the phosphine catalyzed intramolecular Morita Baylis Hillman

reaction.

Scheme 1.9. First intramolecular Morita Baylis Hillman reaction carried out by Fráter.

CHO

∗EWG

OHPR3

EWG

n

CHO

∗

EWG

nR3P

∗

∗

∗EWG

OH

R3Pn

nXIII

XIVXVI

XVII

∗

∗

∗EWG

O

R3Pn

XV

O HO25 mol%

75%, 24 h

XIX

EtO

O

EtO

O

XVIII

PBu3


During the period from 1999 to 2006, Murphy published four reports detailing systematic

investigations of ring closing Morita Βaylis Hillman reactions.20,24-26 He found that phosphines,

usually 20-30 mol% of PBu3, were generally good choices for the intramolecular reaction. He also

employed amines or thiolates as catalysts but the product yields were lower or the reactions did not

occur at all. A typical cyclization is depicted in Scheme 1.10.

Scheme 1.10. Representative reaction reported by Murphy.

Keck investigated the same reaction in 2002 with a substrate similar to XIII (Scheme 1.10),

but with R equal to SEt.27 Employing 10 mol% of P(CH3)3, he obtained 82% yield of a thioester

alcohol after 15 h.

Also Koo published a communication in 2004 reporting PPh3 promoted reactions similar to

those in Scheme 1.10.28 However, he employed one equiv. of the phosphine. Under optimum

conditions and using a reactive substrate that gave a five-membered ring system, it took 12 h to

obtain the product in 98% yield. Many substrates needed longer reaction times and gave lower

yields.

Noteworthy here is a further publication from Miller, this time in the year 2005.29 He

reported an amine catalyzed intramolecular Morita Baylis Hillman reaction with a complex co-

catalyst system. He employed a catalyst mixture of 20 mol% of pipecolinic acid and 10 mol% of a

particular scalemic peptide. The best yield he obtained was 82%. Even more important was the ee

of 80% he obtained. With a subsequent kinetic resolution of the scalemic product mixture, he was

able to isolate a product in 50% yield with > 98% ee.

CHO

HO

20-30 mol%

PBu3

58-80%, 5-16 h

XVIIEWG = R(CO)

R

O

R

On = 1,2

n = 1,2

XIIIEWG = R(CO)


1.5 Future Directions

The Morita Baylis Hillman reaction, particularly the intramolecular variant, offers a

tremendous breadth with regard to substrate diversity and product scope. In Figure 1.2 the highly

functionalized product molecule XVII is depicted.

Figure 1.2. Key features of the highly functionalized intramolecular Morita Baylis Hillman product

XVII.

Importantly, the product molecule XVII features three different groups. Many further

reactions at these groups are conceivable. The alcohol could be alkylated. If the EWG features a

carbonyl (R(CO)) group, 1,2-addition, 1,4-addition, or reduction to a second allylic alcohol center

could be effected. The double bond could be stereoselectively hydrogenated leading to a second

stereocenter. Or the double bond could be oxidized selectively to a glycol again leading to a triol

with three adjacent stereocenters.

This stereocenter is embedded in a rigid skeleton formed by a five- or six-membered ring

system. Hence, after modification of the functional groups, such molecules could be useful for

docking to receptors, leading to pharmaceutical applications. Therefore, it is critical to develop

reliable synthetic pathways leading to such molecules, ideally with high stereoselectivity.

It was and it will be a challenge to synthesize molecules of the type XVII. In the past the

Morita Baylis Hillman reaction often had slow reaction rates associated with low yields. High

substrate as well as solvent dependencies were found. Furthermore, at the outset of this work in

∗EWG

OH

nXVII

Three functional groups

Rigid skeleton

Stereocenter


2004, there were no satisfying chiral catalysts for the enantioselective formation of these products.

Therefore, we asked whether it would be possible to develop highly reactive catalysts

leading to satisfying product yields. Additionally, the catalyst should provide high


A second target was to find a way to recycle the catalyst. Until now there is only one

publication dealing with the recycling of a catalyst for the Morita Baylis Hillman reaction.30 It was

released while this work was going on. However, it involves a totally different catalytic system than

that employed within this work, as detailed in section 4.3.

2

Enantioselective Organocatalysis with Rhenium-Containing Phosphines

2.1 Introduction

In the last few decades there have been many publications involving rhenium complexes.

Rhenium-containing phosphines are distinguished by one or more non-coordinating PR2 moieties,

and were first reported by Gladysz and Buhro.31 The general structure of the rhenium center

featured in this early work is depicted in Figure 2.1. Such complexes are often termed "chiral at

rhenium". However, detailed information regarding the enantioselective synthesis of the rhenium-

containing phosphines employed in this chapter are given in Chapter 3. In the following text some

structural and electronic attributes are highlighted, followed by representative rhenium complexes

that have been applied in catalytic reactions other than those treated in Chapter 1.

Figure 2.1. General idealized structures of the rhenium fragment [(η5-C5H5)Re(NO)(PPh3)]+ (A)

and (η5-C5H5)Re(NO)(PPh3)(X) (B), upon which many rhenium complexes are based.

Structure A in Figure 2.1 shows the d-orbital HOMO of the fragment [(η5-

C5H5)Re(NO)(PPh3)]+. This is a sixteen valence electron species and therefore this fragment is a

strong Lewis acid with attractive interactions.32 A variety of adducts with Lewis bases X– have

been reported (B, Figure 2.1). On the other hand, the rhenium fragment is a π-base as well, as the d-

ON PPh3

Re

PPh3

ON

X

125°

125°90°

90°

A B

14 2 Catalysis with Rhenium-Containing Phosphines

orbital HOMO can donate into the π-acceptor system of subsequently bound ligands. Of course, this

donating effect is also present if groups X without low-lying π-acceptor orbitals are bound. This has

particular consequences when such ligands also feature a lone pair, as sketched in the generalized

structure C in Figure 2.2. Repulsive interactions should result between the occupied orbitals, i.e. the

ligand's lone pair and the d-orbital HOMO.31,33 This explains the experimentally observed

increased basicity of the ligand's lone pairs.

Figure 2.2. Key orbital interactions in coordinatively saturated octahedral LnMPR2 (C) and

LnMCH2PR2 (D, E) complexes.

Increased basicity is also observed when a methylene spacer is present between the metal

center and the lone pair bearing atom. The two relevant interactions are illustrated in structures D

and E. Structure D depicts the repulsive interaction between the filled metal-carbon σ-orbital and

the phosphorus lone pair. This results in an enhanced energy, and therefore enhanced basicity and

nucleophilicity, of the phosphorus lone pair. This effect is exactly analogous to the increase of

carbon basicity and nucleophilicity in allyl silanes.34 The other orbital interaction shown in

structure E involves the metal d-orbital HOMO and the carbon phosphorus σ*-orbital. This filled-

empty (attractive) interaction serves to decrease the carbon phosphorus bond order, putting more

electron density on the phosphorus atom and raising the lone pair orbital energy.

These effects were evidenced by the simple experiment depicted in Scheme 2.1.35

L

L

PL

L

L

RR

C

repulsive:metal d-orbital HOMO / phosphorus lone pair

D

repulsive:σ-orbital /

phosphorus lone pair

E

attractive:metal d-orbital HOMO /

σ*-orbital

L

L

L

L

L

P

L

L

L

L

L

CC

P

2 Catalysis with Rhenium-Containing Phosphines 15

Scheme 2.1. Enhanced basicity of the lone pairs of (η5-C5H5)Re(NO)(PPh3)(CH2SCH3) (1).

When the thioether 1 was mixed with the cationic sulfonium salt 2 an equilibrium developed

and the reaction shifted to the side of the cationic sulfonium salt 3 and the free thioether dimethyl

sulfide. This showed that 1 is a stronger base towards [(η5-C5H5)Re(NO)(PPh3)(=CH2)]+ than

dimethyl sulfide, proving the enhanced basicity of the sulfur atom lone pairs in 1.

Going back to Figure 2.1, someone could guess naively that the fragment B has a tetrahedral

structure (four ligands). In fact it is formally an octahedral structure wherein the cyclopentadienyl

ligand occupies three coordination sites of the rhenium center. Therefore, the angles between the

other three ligands are all formally 90°. However, these angles differ in reality by up to several

degrees, which could effect product stereoselectivities.

Summarizing these characteristics, there is a spectator metal center that enhances electron

density at the catalytically active Lewis base center, and hence greater reactivity is anticipated.

Second, the chiral rhenium center with its three different sized ligands (η5-C5H5, PPh3, and NO)

provides the possibility of enantioselective catalysis. In view of the octahedral geometry, there are

significantly different bond angles as compared to analogs with carbon stereocenters.

There has been a long tradition in employing this fragment for catalysis within the Gladysz

group. Some catalytically active rhenium-containing monophosphines are summarized in Figure 2.3.

ON PPh3Re

H2C

S

CH3

ON PPh3Re

H2C

S

CH3

CH3

ON PPh3Re

H2C

S

ON PPh3Re

CH2

CH3

S

CH3

CH3

1 2 3


Figure 2.3. Rhenium-containing monophosphines that have been employed successfully in

catalysis.

Compounds 4-6 were successfully employed for the Suzuki coupling reactions of PhBr with

phenyl boronic acid.36 For this 4-6 were generated in situ from the corresponding conjugate acid,

the phosphonium salt, using t-BuOK as a base. Then Pd(OAc)2 was added and the resulting

palladium-phosphine adducts were utilized for catalysis without isolation. Biphenyl was formed in

57% to 99% yields. Typically 4 mol% of ligand 4-6 and 1 mol% of Pd(OAc)2 were utilized. These

catalytic systems tolerated many differently substituted bromophenyl substrates.

Catalyst 7 was employed for Suzuki coupling reactions with the above mentioned

substrates.37 It is a bidentate species that is easily synthesized via cyclometalation and subsequently

isolated. Catalyst 7 gave product yields of 86% to 99%. It is a very reactive species and turnover

numbers of nearly 100000 have been reached.

Rhenium-containing diphosphines that are functionalized at the cyclopentadienyl moiety

have been synthesized. These have been used as chelate ligands for rhodium and palladium

catalysts. Selected catalyst precursors are depicted in Figure 2.4.

Complexes 8-12 in all have a diphenylphosphinocyclopentadienyl ligand, η5-C5H4PPh2. An

H2C

Ph3P Re ∗

ONPd

Ph2P

Br

2

ON PPh3Re∗

PR2

ON PPh3Re∗

CH3

R2P

OC CORe∗

CO

R2P

4 5

6 7


additional PPh2 group was coordinated to the rhenium directly (9, 12) or linked through a single

carbon spacer (8, 10, 11, and 13).

Figure 2.4. Adducts of rhenium-containing diphosphines that have been employed successfully in

catalysis.

Hydrosilylations of aromatic ketones were successfully carried out with catalysts 8, 9, and

PPh2

NORe∗

PPh3

Ph2P

RhCH2

NORe∗

PPh3

Ph2P

Rh

Ph2P

PPh2

NORe∗

PPh3

Ph2P

Pd

CH2

NORe∗

PPh3

Ph2P

Pd

Ph2P

Cl

Cl

Cl

Cl

CH∗

NORe∗

PPh3

Ph2P

RhPh2P

Ph

ON PPh3Re∗

H2C

P

NOPh3PRe∗

H2C

NOPh3PRe∗

CH2

P

ON PPh3Re∗

CH2

Rh

8 9

10 11

12

13

0,1


10. After workup the corresponding scalemic alcohols were obtained with ee values ranging from

11% to 92% and good yields (50-83%).38,39 Hydrogenations of protected dehydro amino acids

were also performed with catalysts 8, 9, and 10 resulting in good yields (70-98%) of products and

with good to excellent enantioselectivities (40-98% ee).39 Arylations of dihydrofuran were achieved

with palladium based catalysts 11 and 12. However, the best yield was 84% and the highest ee

12%.40

Catalyst 13 contains four rhenium fragments, each of which is singly bonded to a

phosphorus center through a methylene spacer. As the phosphorus centers are bridged by (CH2)n

spacers, a bidentate ligand for the active rhodium center is obtained. This molecule was screened

with a large variety of reactions. These included hydrogenations of protected dehydro amino acids

and hydrosilylations of aromatic ketones. The conversions ranged from 32% to 99%; unfortunately

products with low enantioselectivities were always obtained (0-33% ee).41


2.2 The Intramolecular Morita Baylis Hillman and Rauhut Currier Reaction: First

Experiments

2.2.1 Results

2.2.1.1 A First Reaction Series

The starting point of this work was the well known racemic complex (η5-

C5H5)Re(NO)(PPh3)(CH2PPh2) (14a)38 and the substrate C1Ph for the intramolecular Morita

Baylis Hillman reaction (Scheme 2.2). Murphy had established that C1Ph reacts smoothly with the

catalyst PBu3 (Scheme 1.10).25

Scheme 2.2. First intramolecular Morita Baylis Hillman reactions with C1Ph and 10 mol% of 14a,

carried out in different solvents.

For all test reactions in this chapter the following sequence and conditions were employed,

unless noted. First, the reaction mixtures were always 0.050 M in substrate and 0.0050 M in catalyst.

Higher concentrations resulted in more side products while lower concentrations decreased the

reaction rate and rendered NMR monitoring more difficult. The reactions were carried out at room

temperature. In some cases, product formation was monitored. One method was by 1H NMR, using

CH2ClCH2Cl (δ(ppm) = 3.73) as internal standard. For such experiments, reactions were conducted

in a NMR tube under N2. The tube was transferred regularly to the NMR spectrometer. In other

CHOPh

OO

Ph OH

10 mol%

ON PPh3Re

CH2PPh2

C1Ph C1Phprod

14a


cases, product formation was monitored by GC. For such experiments, 0.050 mL aliquots of the

reaction solutions were removed and added to the ethyl acetate solutions of decane, which served as

an internal standard. More information about the monitorings are detailed in section 2.5.2. The

curves shown in all rate profiles were calculated by standard fitting methods.

2.2.1.2 Solvent Dependency

The reaction in Scheme 2.2 was carried out in several solvents. Only the reactions in

CH3CN, CH2ClCH2Cl, PhCl, or C6H6 were successful. Data obtained by GC or NMR monitoring

as described above are given in Figure 2.5.

Figure 2.5. Reaction profiles for the formation of C1Phprod in Scheme 2.2 in different solvents.

The purple graph (♦) shows for comparison the reaction of C1Ph with 10 mol% of PPh3 in

CH2ClCH2Cl.

In general, nonpolar solvents gave faster reactions. The optimum solvent rate-wise was

0 40 80 120 1600

20

40

60

80

Prod

uct Y

ield

(%)

Time (h)

CH3CN

CH2ClCH2Cl / t-BuOH

C6H6

PhCl CH2ClCH2Cl

CH2ClCH2Cl / PPh3


C6H6 (●); the substrate was fully consumed after ca. 1 h. In PhCl ( ) the reaction was comparable

but a little slower (2 h). It was much slower in CH2ClCH2Cl (■; 120 h) but the reaction went to

completion anyway. A mixture of CH2ClCH2Cl and t-BuOH (▼) rapidly initiated catalysis but the

yield of product reached a maximum of 30% after 20 h. Much substrate remained unconsumed. In

general, in the presence of an alcohol additive, the reaction was much slower or the selectivity

decreased dramatically. Often many unassigned side products were found in addition to unreacted

substrate. The reaction in CH3CN (▲) is depicted above but it did not go to completion also.

Furthermore, many side products were detected by GC but were not further investigated.

To compare the effect of the rhenium fragment upon activity, a comparison experiment with

PPh3 was conducted in CH2ClCH2Cl (♦). As shown in Figure 2.5, reaction was much slower. The

experiment was terminated after one week of reaction time with ca. 20% yield and much

unconverted substrate.

2.2.1.3 Temperature Dependency

Since the reaction in CH3CN gave many side products, a lower temperature was

investigated in hopes of increasing selectivity. Data are shown in Figure 2.6.

Surprisingly, product formation appeared faster initially. However, the starting material was

consumed after 25 h, at which time the product yield was only 25%. Many more side products than

at room temperature were noted. This showed that for optimization purposes CH3CN seemed to be

the wrong solvent.

As the reaction in CH2ClCH2Cl gave few side products, the temperature was raised and the

effect upon rate assayed. Data are given in Figure 2.7. This shows that raising the temperature to 40

°C in CH2ClCH2Cl decreases the rate of product formation. The catalyst was inactive after several

hours and gave only 20% product as analyzed by GC. These measurements further showed that

there was much substrate left beside some unknown side products. To exclude a temperature

dependent equilibrium, a CH2ClCH2Cl solution of C1Phprod and 14a (10 mol%) was kept at 40 °C

for 24 h. No reaction occurred, as assayed by 1H NMR and 31P{1H} NMR spectroscopy.


Figure 2.6. Reaction profiles for Scheme 2.2 at room temperature (▲) and 0 °C (■) in CH3CN. The

former experiment is repeated from Figure 2.5.

Figure 2.7. Reaction profiles for Scheme 2.2 at room temperature (▲) and 40 °C (■) in

CH2ClCH2Cl. The former experiment is repeated from Figure 2.5.

0 50 100 1500

10

20

30

40

50P

rodu

ct Y

ield

(%)

Time (h)

rt

0 °C

0 20 40 60 80 100 120 1400

20

40

60

80

Prod

uct Y

ield

(%)

Time (h)

40 °C

rt


The catalyst 14a, as well as C1Phprod remained. An independent NMR experiment, wherein a

CH2ClCH2Cl solution of 14a was kept at 40 °C overnight, showed the ruggedness of the catalyst

under such conditions.

Similar experiments with C1Ph and 14a in PhCl but with a temperature gradient (–20 °C to

room temperature, 12 h) showed only the formation of side products. As a result of these

experiments, an ambient reaction temperature was judged to be optimal. For practical reasons this

meant a temperature range of 20-25 °C for all experiments that were carried out at room

temperature. If the ambient temperature exceeded 25 °C, a cryostat was employed to cool the

mixtures to 20 °C.

2.2.1.4 Substrate Dependency

Given the superiority of C6H6 and PhCl as solvents established in the previous section,

several substrates were tested. These substrates and their abbreviations are summarized in Figure

2.8. References are given for the substrates that are known from the literature; all others are new

and their syntheses are presented in Chapter 5. Their Morita Baylis Hillman products are also

depicted, but not all of them could be obtained with the employed catalysts in this chapter.

Several of those substrates were tested in PhCl with the conditions of Scheme 2.2 (10 mol%

14a). The reaction profiles are given in Figure 2.9. In the course of this work a set of substrates was

found that showed excellent reactivity. These were C1Ph, C1(p-Tol), C1Me, C1S(i-Pr), C2(p-Tol),

C2Me, C1Ph2, and C1S(i-Pr)2. The others (C1OMe, C1OEt, C2OMe, C2OEt, C2Ph, C2(p-Tol)2,

and C2Me2) showed only low or even no reactivity.

It was found that the Morita Baylis Hillman substrates C1(p-Tol) ( ) and C1Ph (■) were

very quickly transformed into their products (3 h and 2 h respectively). The yield in the latter

reaction was slightly lower (95% vs. 90%). The Rauhut Currier substrate C1Ph2 (▼) also showed a

fast reaction, and product formation was complete within 3 h. Both C1Me ( ) and C2(p-Tol) (□)

reacted more slowly, with maximum product yields achieved after 22 h and 48 h, respectively. The

reaction with C1S(i-Pr) (▲) was less selective, as after 29 h the substrate had been consumed, but


the product yield was only 50%.

The reaction rates increased when the solvent PhCl was replaced by C6H6. The data are

shown in Figure 2.10, with all other conditions the same as before. The data in PhCl are repeated

from Figure 2.9.

Figure 2.8. Substrates employed herein for catalytic reactions, and product structures. Substrates

with n = 1 (C1R, C1R2) give products with five-membered rings (C1Rprod, C1R2prod) and with n

= 2 (C2R, C2R2) give products with six-membered rings (C2Rprod, C2R2prod). Many have already

been reported in the literature: C1Ph,25,28,42,43 C2Me,44 C1Ph2,19,20,26,45 C1OEt,25 C1OMe,46-48

C2OEt,25,46,49 C2OMe,47,48 C2Ph,25 C1Me,28 C1(p-Tol),42,43 C2Me2,26 and C1Me250).

In the case of substrate C2(p-Tol) the reaction rate was only slightly increased by the usage

of C6H6 (red traces, □). For C1Ph this effect was stronger (black traces, ■) and for the substrate

CHOR

On = 1,2

Morita Baylis Hillman substrates

R

O

n = 1,2

R

O

Rauhut Currier substrates

C1Ph, C1S(i-Pr), C1OMe, C1OEt, C1Me, C1(p-Tol)C2(p-Tol), C2Me, C2OMe, C2OEt, C2Ph

C1Ph2, C1S(i-Pr)2, C1Me2

C2(p-Tol)2, C2Me2

CnR CnR2

R

OOH

R

O

R

O

CnRprod CnR2prod

Morita Baylis Hillman products Rauhut Currier products

n = 1,2

n = 1,2



Scheme 2.2 in PhCl; the data for C1Ph are repeated from Figure 2.5.


Scheme 2.2 in PhCl and C6H6; the data for C1Ph involving PhCl are repeated from Figure 2.5.

0 20 400

20

40

60

80P

rodu

ct Y

ield

(%)

Time (h)

C1Ph

C1(p-Tol)

C1Ph2

C1Me

C2(p-Tol)

C1S(i-Pr)

0 5 10 150

20

40

60

80

( ) C1Ph

( ) C1S(i-Pr)

( ) C2(p-Tol)

Pro

duct

Yie

ld (%

)

Time (h)

C6H6

PhCl C6H6

C6H6

PhCl

PhCl


C1S(i-Pr) it was significantly higher (green traces, ▲). This meant for the latter substrate a reaction

time of ca. 6 h (C6H6) vs. 30 h (PhCl) and furthermore nearly a doubling of the yield (90% vs.

50%).

Two more substrates were tested in C6H6 (C1Ph2, C1S(i-Pr)2). Also these gave very good

yields (92%, 98%). These data are given in the experimental to keep Figure 2.10 more tractable.

Next it was sought to ascertain how the catalyst could be optimized. For this, previously

synthesized rhenium-containing phosphines were screened.

2.2.1.5 Reactions with Other Rhenium-Containing Phosphines

The next series of experiments utilized different rhenium-containing phosphines, as

summarized in Figure 2.11. All complexes except one had been previously characterized either in

the literature ((SReSC)-15a,51 (SReSC)-16a,51 and (S)-16b38) or a doctoral dissertation ((SReSp)/

(SReRP)-17a,b52). The synthesis of (SReSC)-15b is described in Chapter 3.

Figure 2.11. Rhenium-containing phosphines that were screened as catalysts.

In comparison to catalyst 14, 15 and 16 have a second chiral center at the carbon spacer.

Furthermore, the complexes 16 are distinguished by a second PPh2 group. The complexes 17 also

feature a phosphorus stereocenter.

All following reactions were conducted in PhCl and monitored by 1H NMR. The reaction of

the catalysts 15 with the substrates C2Me, C2Ph, C2OEt, and C1OEt showed no formation of the

ON PPh3Re∗

∗

(SReSC)-15a: R = Ph

(SReSC)-15b: R = CH3

RPh2P

H

ON PPh3Re∗

∗RPh2P

H

(SReSC)-16a: R = Ph

(S)-16b: R = H

PPh2

ON PPh3Re∗

CH2PRR'∗

(SReSP)/(SReRP)-17a: R/R' = Cy/Ph

(SReSP)/(SReRP)-17b: R/R' = Cy/t-Bu


target products. These substrates were recovered after 168 h, together with a smaller amount of side

products. Only the substrate C1Ph was converted. However, the reactivity of the phenyl-substituted

catalyst (SReSC)-15a was so low that only ca. 10% of the C1Ph was transformed into the cyclic

product within 120 h. Much substrate was unconverted (ca. 80%) and some side products were

found. The methyl-substituted catalyst (SReSC)-15b was somewhat more reactive towards C1Ph as

shown in Figure 2.12. However, in comparison to catalyst 14a very long reaction times were

required (ca. 144 h vs. 2 h).

Figure 2.12. Reaction profile for the cyclization of C1Ph with 10 mol% of (SReSC)-15b in PhCl.

The diphosphine catalysts 16a,b were similarly tested. As shown in Figure 2.13, (S)-16b

exhibited some reactivity, although the amount of product obtained was still lower than with

(SReSC)-15b. After one week, the product was present in 40% yield. Some starting material as well

as side products were detected.

The other substrates (C2Me, C2Ph, C2OEt, and C1OEt) were recovered after 168 h,

together with lower amounts of side products. The complex (SReSC)-16a was totally inactive.

Next, complexes 17a,b were screened as catalysts. For these compounds, the corresponding

0 50 100 150 2000

20

40

60

80

Pro

duct

Yie

ld (%

)

Time (h)


phosphonium PF6– salts52 were first treated with t-BuOK. After filtration through Celite® the crude

red compounds 17a,b were precipitated with n-pentane and used without further characterization.

The diastereomeric excesses (de) of (SReSP)/(SReRP)-17a and (SReSP)/(SReRP)-17b were 91% and

80%, respectively (predominantly SReSP, each).

Figure 2.13. Reaction profile for the cyclization of C1Ph with 10 mol% of (S)-16b in PhCl.

Complex (SReSP)/(SReRP)-17b showed only low reactivity. In the best case (C1Ph), only

traces of product were detected after 168 h. The 1H NMR analyses showed much unconverted

substrate. The substrates C2Me, C2Ph, C2OEt, and C1OEt gave even poorer results. In contrast,

(SReSP)/(SReRP)-17a, in which the t-butyl group of (SReSP)/(SReRP)-17b has been replaced by a

phenyl, showed appreciable reactivity towards C1Ph and C2Me. The reaction data are depicted in

Figure 2.14. In the case of C1Ph, the first NMR assay was carried out after 24 h; the reaction may

have been complete earlier. But anyway the data for C2Me show a much longer reaction time as

compared to 14a (168 h vs. 2 h).

Finally, the rhenium-containing phosphine (η5-C5H5)Re(NO)(PPh3)(PPh2) (18)38 without a

spacer group was tested. The active phosphorus center should be more electron rich as analyzed in

0 50 100 150 2000

20

40

60

80

Pro

duct

Yie

ld (%

)

Time (h)


section 2.1, and therefore higher reactivity was expected. However, the catalyst was consumed

rapidly and no product was detected. Thus, it seemed that this phosphine was too reactive.

Figure 2.14. Reaction profiles for the cyclizations of C1Ph (■) and C2Me (∆) with 10 mol% of

(SReSP)/(SReRP)-17a in PhCl.

2.2.1.6 Enantioselective Catalyses

As all of the rhenium-containing catalysts that are mentioned above have at least a rhenium

stereocenter, and can be synthesized with a single rhenium configuration, there is the possibility to

perform enantioselective catalysis. The substrate C1Ph was screened with 10 mol% of several

catalysts in PhCl. The ee values of the product C1Phprod are summarized in Table 2.1. The absolute

configuration of the dominant enantiomer was not determined.

This table shows that the best catalyst is (S)-(η5-C5H5)Re(NO)(PPh3)(CH2PPh2) ((S)-14a).

Two other catalysts ((SReSC)-15b, (SReSP)/(SReRP)-17a) gave somewhat lower ee values and one

gave a product that was nearly racemic ((SReSC)-16b). Furthermore, for the catalysts that gave

0 50 100 150 2000

20

40

60

80

Prod

uct Y

ield

(%)

Time (h)

C1Ph

C2Me


lower ee values, the reaction rates were also slow (Figures 2.12, 2.13, and 2.14).

To investigate the scope of the best catalyst from Table 2.1, analogous reactions were

conducted with 10 mol% of (S)-14a and a variety of substrates in two solvents, C6H6 and PhCl. The

results are shown in Table 2.2.

Table 2.1. Product ee values for reactions of C1Ph with 10 mol% of enantiopure catalysts in PhCl.

Catalyst

(S)-14a (SReSC)-15b (SReSP)/(SReRP)-17aa

(SReSC)-16b

ee(C1Phprod) 45% 28% 35% 3%

a 91% de.

Table 2.2. Product ee values for reactions of various substrates with 10 mol% of (S)-14a in C6H6

and PhCl.

Solvent

C6H6 PhCl

ee(C1Phprod) 62% 45%

ee(C1S(i-Pr)prod) 74% 62%

ee(C2(p-Tol)prod) 38% 38%

ee(C2Meprod) 70% 47%

ee(C1Ph2prod) 42% 56%

ee(C1S(i-Pr)2prod) 52% ----a

a This value was not determined.

With a single exception (C1Ph2prod), the best results were obtained in C6H6. In every case,

reaction was faster in C6H6. Finally, analogous reactions of C1Ph and C1S(i-Pr) with racemic 14a

proceeded at similar rates.


2.2.2 Discussion

2.2.2.1 Solvent Dependency

The mechanism of the intramolecular Morita Baylis Hillman reaction was shown in Scheme

1.8. An activated carbon-carbon double bond undergoes nucleophilic attack by the catalyst. The

resulting enolate reacts with an aldehyde group. In former times it was supposed that this step

should be rate determining,53 while newer publications discuss the proton shift, occurring prior to

the elimination step, as rate determining.54,55 This remains to be clarified, and in any event may not

apply to intramolecular reactions where the aldehyde is already connected to the enolate.

The Morita Baylis Hillman reaction is known to be very solvent dependent. For example,

Koo conducted the reaction with substrate C1Ph and a stoichiometric amount of PPh3 in t-BuOH

and stirred this mixture at room temperature for 6 h.28 Their reaction in CH3CN on the other hand

needed 22 h. Up to this point, protic and/or very polar solvents were thought to be optimal for

Morita Baylis Hillman reactions, as the very polar zwitterionic intermediates have to be stabilized

during the reaction cycle (Scheme 1.8).

At the outset of this work, the Koo conditions were applied but with 10 mol% (η5-

C5H5)Re(NO)(PPh3)(CH2PPh2) (14a) in place of one equiv. of PPh3. Unfortunately, 14a is only

very slightly soluble in t-BuOH. To improve the solubility, CH2ClCH2Cl was added. A 1:1 v/v

mixture afforded adequate solubility and the reaction of C1Ph gave nearly a 30% yield of C1Phprod.

Some substrate was unconverted and many (unassigned) side products were detected by GC. The

protic solvent and/or hydrogen bonds derived therefrom were viewed as a possible origin of these

side reactions. In contrast, the literature experiments with PPh3 as "catalyst" in t-BuOH gave hardly

any side products.28

Catalyst 14a also gave much slower or no reactions in the presence of other alcohol

additives such as CF3CH2OH and BINOL. Thus, a protic solvent or cosolvent seems to be a bad

choice for catalyst 14a. Other polar solvents were sought that could dissolve the catalyst. CH3CN

was selected. However, many side reactions were detected.


Given the data in Figure 2.5, solvents with lower polarities were screened. As shown, good

yields could be obtained with CH2ClCH2Cl, which was used as a cosolvent before. However, the

reaction time was quite long. The experiments in PhCl gave better results concerning reaction time

and yield, and the best results were obtained by employing C6H6 as solvent (Figure 2.10). A

"ranking" of the solvents is shown in Figure 2.15.

Figure 2.15. Top rated solvents for the intramolecular Morita Baylis Hillman reactions described

herein and their dielectric constants.

This stands in sharp contrast to the usual solvents reported in most literature sources.10 It

seems that the rhenium-containing phosphine 14a can better promote the above mentioned reaction

in less polar solvents. The dielectric constants of the employed solvents are also summarized in

Figure 2.15 as one quantitative measure of their polarities.56

Possibly it is less necessary to stabilize polar intermediates in reactions catalyzed by 14b.

For example, the zwitterionic intermediates might have intramolecular charge-charge interactions

that somehow lower the energy, as sketched in Figure 2.16.

Figure 2.16. Possible substrate-catalyst interaction that may be a factor in solvent rate trends.

(worst) CH3CN < CH2ClCH2Cl << PhCl < C6H6 (best)

(more polar) (37.5) (10.4) (5.5) (2.3) (less polar)

rhenium-

containing

catalyst

O

R

covalent

bond

R'

bipolar

interaction

substrate


2.2.2.2 Temperature Dependency

As noted above, many side products accompany the intramolecular Morita Baylis Hillman

reaction of C1Ph in CH3CN. Since 14a is an effective catalyst for the nitroaldol reaction,57 in

which it is believed to act as a Brønsted base, aldol and related condensation products might form.

Since selectivities often increase at lower temperatures, the reaction with 14a was carried out at 0

°C. However, no significant improvement was realized, though the reaction seemed to run faster at

the beginning. Previous studies have shown that the Morita Baylis Hillman reaction rate can be

increased in special cases by lower temperatures.58

In this context, the first enolate generated, a zwitterionic structure like XIV (Scheme 1.8)

could be syn or anti configured (XIVa, XIVb). The syn isomer XIVa may be more stable, as the

charges are closer together, while the anti one XIVb is less stable. The less stable isomer might

react more rapidly with aldehydes to give side products. At lower temperature, the enolate

selectivity might be increased, and/or reactions of XIVb might be suppressed.

2.2.2.3 Substrate Dependency

To delineate the scope of the catalyst 14a, the different substrates in Figure 2.8 were tested.

A distinct substrate dependency was found.

First, the five-membered ring products always formed much faster than the six-membered

ones. This is nicely illustrated for the substrates C1(p-Tol) and C2(p-Tol) in Figure 2.9. This may

reflect a more favorable exo-trig transition state for the cyclization step XIV→XV in Scheme 1.8.59

Other results were less clear cut. For example, C1Ph was transformed quickly to C1Phprod

while C2Ph gave no C2Phprod at all. In the latter case, 31P{1H} NMR monitoring showed

complete consumption of catalyst 14a (CH2PPH2, 8.1 ppm). Instead, several signals at ca. 50 ppm

were detected, suggesting a positively charged phosphorus atom.

Not only the chain length of the substrates plays an important role but also the nature of the

electron withdrawing group (EWG) in Schemes 1.5 and 1.8. If the group is polarizable (Ph(CO), p-


Tol(CO)) with a distinct ability to delocalize electron density, good reactivity was obtained. Also

the methyl-substituted substrates showed good reactivity.

Other substrates, for example all alcohol derived esters, were very unreactive and full

conversion to the product was never obtained. In contrast, if the alkoxy group was substituted by a

thioalkoxy group (C1S(i-Pr)), the substrate reacted smoothly. Sulfur is of course less

electronegative and more polarizable than oxygen. However, the reason for the much improved

yields remains unclear. The subtle electronic differences between ketone, ester, and thioester

enolates may play a role.

2.2.2.4 Formation of a Side Product

Not all substrates in Figure 2.8 were investigated in detail. There were several reasons. For

example, C1Me was very unstable as a pure compound and even decomposed upon storage at low

temperatures (–70 °C). After four weeks, a very viscous oil was obtained. It is supposed that

addition and condensation products and/or polymers were obtained. On the other hand the bis

(methyl ketone) C1Me2 (Scheme 2.3) showed acceptable stability, but the yields of C1Me2prod

were quite low. A chromatographic workup of the reaction of C1Me2 with 10 mol% 14b (see

section 2.3.1.1) in PhCl at room temperature showed that C1Me2prod subsequently reacted to give

the aldol side products 19 and 20.

The product 20 had been previously reported by Roush.60 Similar to this work, the synthesis

involved an aldol reaction of C1Me2prod that had been prepared by a Rauhut Currier reaction. The

identity of 20 was established by 1H NMR and 13C{1H} NMR spectroscopy. The aldol intermediate

19 has not been previously reported and the structural assignment rests solely on 1H NMR and

13C{1H} NMR. When consumption of C1Me2 was complete, the crude mixture was analyzed by

1H NMR, which indicated the product ratio in Scheme 2.3. The desired product C1Me2prod

dominated.


Scheme 2.3. Formation of cyclic side products 19 and 20 from the reaction of C1Me2 with 10

mol% 14b in PhCl.

Note that in principle C1Me2prod could undergo a second type of intramolecular aldol

reaction. Murphy showed this to be the major isomer when C1Me2prod was treated with base as

opposed to a nucleophilic catalyst.20 Interestingly, such products were not detected.

2.2.2.5 Oxidation of the Catalyst

In the course of many catalytic experiments, the phosphine oxides of 14a61 and other

catalysts were often detected by 31P{1H} NMR spectroscopy when the reaction was complete.

There are several possible explanations for this.

All solvents were carefully freeze pump thaw degassed. However, some oxygen could be

introduced with the substrate charge. All Morita Baylis Hillman substrates were stored at –70 °C

under air. Most of the substrates are oils or liquids and therefore they could contain dissolved

oxygen. Of course, the samples were evacuated and backfilled with N2 before solvent was added,

O

O

O

O

OO

OH

Aldol Addition Condensation

14b10 mol%

10 : 6 : 1

NMR ratio, crude mixture

C1Me2

C1Me2prod 19 20


but there might be oxygen residues.

Another possibility is that traces of oxygen diffused through the caps or septa as all these

experiments were conducted in Schlenk flasks, NMR tubes, or GC vials. But this is unlikely as

several times parallel to the catalysis experiment a catalyst solution was stored under the same

conditions as the catalysis mixture. In such catalyst solutions phosphine oxide was never found by

31P{1H} NMR. This raises the possibility that oxidation could be effected by the substrates

themselves. A possible sequence is illustrated in Scheme 2.4.

Consider the zwitterionic intermediate 21 (similar to XV, Scheme 1.8). This intermediate

could either eliminate the tertiary phosphine (Morita Baylis Hillman route) to give C1Phprod or

follow a "reductive elimination" route. For this an enolization to 22 must first take place. At the

same time or subsequently, a cyclic intermediate 23 is formed. The driving force would be the

formation of the very stable phosphorus-oxygen bond. Roush also speculated about phosphorus-

oxygen interactions in the intramolecular Rauhut Currier and following aldol reactions, and

suggested an important role in determining the regiochemistry of certain products.60

The organic residue would be released as a cyclopropene or 1,3-dipole. Although these are

high energy species, the formation of the strong phosphorus-oxygen linkage would to some extent

compensate. The amount of catalyst derived organic product must by necessity be small. However,

as shown in Figure 2.17, two alcohols, 24 and 25, which would be logical products from 23, could

be provisionally identified from the reaction of C1Ph and 10 mol% 14a in PhCl at –25 °C.

Curiously, the analogous reaction at room temperature gave much less phosphine oxide and

significantly higher yields of C1Phprod. Both 24 and 25 have been reported in the literature and the

1H NMR data agree well with that in Figure 2.17.62,63


Scheme 2.4. Possible pathway for the formation of catalyst-derived phosphorus oxide.

Figure 2.17. 1H NMR spectrum of side products obtained from the reaction of C1Ph with 10 mol%

14a at –25 °C in PhCl.

O

O

Ph

PR3

H

OH

O

Ph

PR3

OH

O

Ph

PR3

MoritaBaylis Hillman

route

OH

O

Ph

PR3

reductiveelimination

route

O=PR3 + organic products

21 C1Phprod

22 23

ppm 2.03 . 0 4.05.06 . 0 7 . 0

24

25 Ph

OH

H H

H

H

Ph

OH

H

H



The data in Table 2.2 show that appreciable enantiomeric excesses can be obtained with

catalyst (S)-14a. Modification of the aryl substituents of this catalyst that give still higher ee values

are described in section 2.3. However, the data in table 2.1, which involve catalysts with additional

stereocenters, merit a preliminary analysis at this stage. The catalyst (SReSC)-[(η5-

C5H5)Re(NO)(PPh3)(CHCH3PPh2) ((SReSC)-15b) contains a carbon stereocenter that is closer to

the reactive phosphorus center than rhenium. Naively, enhanced enantioselectivities might be

expected. However, the methyl substituent influences a number of other factors, such as the

conformational equilibria sketched in Figure 2.18. Whereas 14a should have two PPh2-CH2Re

conformations of approximately equal energy (14a-I, 14a-II), (SReSC)-15b should have one much

more stable conformer 15-II. Otherwise, a substituent must be placed in the interstice between the

phenyl substituents on phosphorus.

In any event, (SReSC)-15b gives C1Phprod with a lower ee value then (S)-14a. The phenyl-

substituted analog, (SReSC)-15a, gives hardly any product at all. It would have been of interest to

probe the opposite rhenium/carbon diastereomers, both of which are known, but this was not done

due to improved results obtained with simpler systems below (section 2.3).

One might naively assume that a phosphorus stereocenter would result in improved

enantiomeric excess, and there has been much recent interest in P-stereogenic phosphorus.64,65

However, the two complexes initially assayed featured cyclohexyl/phenyl and cyclohexyl/t-butyl

substituents at phosphorus. Lower yields and enantioselectivities were obtained. Perhaps aliphatic

substituents are deleterious, a hypothesis reinforced by improved results with aryl/aryl analogs

below (section 2.4).


Figure 2.18. Newman projections down the Ph2P-CHR[Re] bonds of catalysts 14a and 15.

2.2.2.7 Activity of Different Phosphorus Centers

Some of the catalysts assayed feature diphenylphosphinocyclopentadienyl ligands,

providing a second type of phosphorus center. Figure 2.19 shows a qualitative comparison of the

different types of phosphorus donors screened in reactions of C1Ph. These in turn allow some

tentative qualitative conclusions.

The phosphorus center of (S)-14a is the most active one. Introduction of the phenyl group at

the spacer ((SReSC)-15a) inactivates center 1' as sketched above. If catalyst (SReSC)-16a is also

inactive, someone could guess that also center 2 is inactive. In contrast, (SReSC)-16b showed some

activity which could then be attributed to center 1. Since there is lower reactivity compared to (S)-

14a, perhaps steric demand of the diphenylphosphinocyclopentadienyl ligand hinders the approach

of substrate to the active center 1. A possible model is illustrated in Figure 2.20. The

diphenylphosphinocyclopentadienyl moiety would be expected to prefer the interstice between the

NO and the methylene group.

PhPh

H[Re]

H

PhP

Ph

[Re]H

H

P

PhP

Ph

[Re]H

R

PhPh

R[Re]

H

P

14a-I 14a-II

PhP

Ph

HH

[Re]

14a-III

PhP

Ph

HR

[Re]

15-I 15-II 15-III

[Re] = (η5-C5H5)Re(NO)(PPh3)

(comparablestabilities)

(most stable)


Figure 2.19. Qualitative comparison of different types of phosphorus donor groups with respect to

reactivity towards C1Ph.

Figure 2.20. Newman like projection down the η5-C5H4PPh2-Re axis of (S)-16b.

The relative basicities of centers 1/1' and 2 are also relevant to this analysis. The reaction

mixture derived from C1Ph and (S)-16b (10 mol%) in PhCl at room temperature was investigated

by 1H NMR and 31P{1H} NMR spectroscopy after 240 h (Figure 2.13). About 40 % of C1Phprod

was detected besides unconverted substrate. The CH2PPh2 phosphorus signal of the catalyst (7.1

ppm) had been replaced by several new signals (45-50 ppm). Possibly, catalyst-substrate adducts

that block the active center formed. However, the phosphorus signal at –17.7 ppm (η5-C5H4PPh2)

was unchanged. This suggests that the latter phosphorus atom might not be involved in the reaction.

To gain additional insight, (S)-16b and HBF4.OEt2 (1 equiv.) were combined in PhCl at room

temperature. The 31P{1H} NMR spectrum showed a dramatic shift for the CH2PPh2 center (7.1

ON

Ph3P

CH2PPh2

PPh2

stericinteraction

(S)-16b

ON PPh3Re

CPh2P H

H

ON PPh3Re

CPh2P Ph

H

ON PPh3Re

CPh2P Ph

H

PPh2

ON PPh3Re

CPh2P H

H

PPh2

center 1 center 1' center 1' center 1

center 2 center 2

observation: activity inactivity inactivity low activity

conclusion: center 1 active center 1' inactive center 2 also inactive center 1 active (but hindered by center 2)

(SReSC)-16a (S)-16b(S)-14a (SReSC)-15a


ppm to 30.3 ppm), consistent with the formation of a phosphonium salt. However, the

diphenylphosphinocyclopentadienyl phosphorus signal remained unchanged (–17.7 ppm). This

suggests that the CH2PPh2 phosphorus atom is the more basic in (S)-16b and should therefore be

more reactive.

2.2.2.8 Conclusions

Conclusions from the experiments in section 2.2.1 can be summarized as follows. The

catalyst (η5-C5H5)Re(NO)(PPh3)(CH2PPh2) (14a) was the most reactive and also gave the highest

enantioselectivities. Substitution of the phenyl groups of the diphenylphosphino center by aliphatic

moieties (17a,b) resulted in lower rates and enantiomeric excesses. Modification of the methylene

spacer (15a,b) showed neither enhanced rates nor enantiomeric excesses. The introduction of a

second phosphorus donor group at the cyclopentadienyl ligand (16a,b) decreased the reaction rates

and the enantiomeric excesses. Therefore, catalysts for future experiments should provide a basic

structure similar to 14a, in which the phenyl moieties of the CH2PPh2 group are replaced by aryl

groups. The successful implementation of this strategy is described in sections 2.3 and 2.4.


2.3 First Series of Improved Catalysts

2.3.1 Results

2.3.1.1 Increased Nucleophilicity by Electron Rich Aryl Substituents

The catalyst 14a effected the cyclization of C1Ph to C1Phprod with short reaction times,

moderate catalyst loadings (10 mol%), and acceptable enantiomeric excesses (up to 62%).

Nonetheless, it was sought to improve on this benchmark. As was concluded in section 2.2.3, the

best way to improve the catalyst might be the modification of the aryl groups at the active

phosphorus center. The new rhenium-containing phosphines assayed are depicted in Figure 2.21.

Figure 2.21. New rhenium-containing phosphines 14b-d.

The phenyl substituents at the active phosphorus atom were substituted in the para positions

by electron donating groups (R = p-Tol (14b), p-C6H4OCH3 (14c), p-C6H4N(CH3)2 (14d)). The

syntheses and characterizations are detailed in Chapter 3.

The reaction profiles for selected Morita Baylis Hillman substrates (C1S(i-Pr), C2(p-Tol),

and C2Me) with the new catalysts (14b,c) are depicted in Figure 2.22. For comparison, the data for

14a in C6H6 (blue traces, ) are repeated for substrates C1S(i-Pr) and C2(p-Tol) from Figure 2.10;

the data for C2Me are new. As supported by the reaction profiles, the new catalysts provide distinct

rate enhancements. The data for C2Me are representative and may be analyzed as follows.

ON PPh3Re

CH2PR2

R = b, p-Tol

c, p-C6H4OCH3

d, p-C6H4N(CH3)2

14


Figure 2.22. Reaction profiles for the cyclizations of various substrates with 10 mol% of 14a-c in

C6H6; the data for C1S(i-Pr) and C2(p-Tol) involving 14a are repeated from Figure 2.10.

Consider the results for the first five hours. The reaction with catalyst 14a is clearly the

slowest (blue trace, ▲). Much faster are catalysts 14c (red trace, ●) and 14b (green trace, ■), which

are quite comparable and likely within experimental error. After ca. 6 h this picture changes. The

reaction with 14a remains slower than that with 14b. Nonetheless, product yields are high in each

case (90% and 85%, respectively). On the other hand, the reaction with 14c slows down and reaches

a maximum product yield of 70%. The other substrates in Figure 2.22 (C1S(i-Pr) and C2(p-Tol))

show similar behavior, as do some uncharted ones (C1Ph, C1Ph2, and C1S(i-Pr)2), for which data

are given in table form in section 2.5.3. However, the reactions with 14b reaches completion earlier

than with 14a.

Added insight into the behavior of 14c is provided by Figure 2.23. Here the consumption of

C2(p-Tol) with catalysts 14a-c is charted, and the product yield data in Figure 2.22 are reproduced.

0 5 10 15 200

20

40

60

80

catalyst:3 ( ) 14a3 ( ) 14b56

( ) 14c

C1S(i-Pr)

C1S(i-Pr)C1S(i-Pr)

C2Me

C2Me

C2Me

C2(p-Tol)

C2(p-Tol)

C2(p-Tol)

Pro

duct

Yie

ld (%

)

Time (h)


Figure 2.23. Reaction profiles for the cyclization of C2(p-Tol) with 10 mol% 14a-c in C6H6.

Conversion refers to the consumption of substrate. The product yield data are repeated from Figure

2.22.

This graphic shows nicely that the more reactive catalyst leads to more side reactions. For

catalyst 14a (blue traces, ▲) the curve for the product yield (rising trace) was nearly symmetric

compared to the substrate conversion (falling trace). Both graphs cross each other at ca. 50%

showing that after consumption of 50% of C2(p-Tol), 50% of C2(p-Tol)prod was obtained.

Additionally, after 72 h (here not explicitly charted) the conversion to product was essentially

complete (99%). This indicated a low rate of side product formation. For catalyst 14b (green traces,

●) the crossing point of both curves is somewhat lower than 50% and the product yield after

complete substrate conversion was only 95%. Obviously, more side reactions were promoted by

14b. The situation with the most reactive catalyst 14c (red traces, ▼) was even more pronounced.

Substrate consumption was fastest and the crossing point is found at ca. 40%. After 24 h, substrate

conversion was complete but the product yield was only 75%. This indicates a much higher

proportion of side products.

Catalyst 14d gave even greater proportion of side products, and for this reason is not charted.

0 10 20 30 400

20

40

60

80

Sub

stra

te C

onve

rsio

n (%

)

Pro

duct

Yie

ld (%

)

Time (h)

catalyst:5 ( ) 14a5 ( ) 14b5 ( ) 14c5

C2(p-Tol)prod

100

80

60

40

20

C2(p-Tol)


Substrate conversions were incomplete, and 31P{1H} NMR indicated deactivation of the catalyst.

Nonetheless, initial rates of product formation were faster than with 14a-c. Table 2.3 summarizes

the product yields obtained with 14d and the other catalysts.

Table 2.3. Product yields for reactions of various substrates with 10 mol% 14a-d in PhCl.

Product yields (1H NMR, %)

Substrate Catalyst

C1Ph C1Me C2OEt C2(p-Tol) C2Me C1OEt C1S(i-Pr)

14a 90c 90c ----e 90 ----e ----d 50b 14b 95 60 ----d 80 65a 30b 70

14c 65a 55 15b 80 60c 45b 70c 14d 20a 20 25a 50 55 20a 35b

a Incomplete conversion, 31P{1H} NMR shows a little remaining catalyst. b Incomplete conversion,

31P{1H} NMR shows some remaining catalyst. c Nearly complete conversion, 31P{1H} NMR

shows a little remaining catalyst. d No reaction. e No data available.

Only in one case was catalyst 14d superior. This was for substrate C2OEt, which always

reacted sluggishly and presumably benefits from the enhanced phosphorus nucleophilicity of 14d.

However, the yield remained low (25%).

Figure 2.10 established that with catalyst 14a, C6H6 was a superior solvent to PhCl for

several substrates. The same effect was also found for catalysts 14b,d. Additionally, product

purities were enhanced in C6H6. Additional data are summarized in table form in section 2.5.3.

The Rauhut Currier substrates C2Me2 and C2(p-Tol)2 gave no reactions with catalysts 14a-

c. However, 14d gave some products, as assayed by 1H NMR spectroscopy of the crude mixtures

(C2Me2prod: 40%, C2(p-Tol)2

prod: 20%).20,60,66 However, due to low yields these products were

never isolated and further characterized although the latter is a new compound. In both cases some

inactivated 14d was detected by 31P{1H} NMR directly after combination of the catalyst and the

substrate solution.



As 14a-c contain a chiral rhenium center, many reactions were also performed with

enantiopure catalysts. The reaction products were assayed for enantiomeric excess by chiral HPLC.

The ee values obtained in C6H6 are summarized in Table 2.4.

Table 2.4. Product ee values for reactions of various substrates with 10 mol% (S)-14a-c in C6H6.

The values for 14a are repeated from Table 2.2.

Catalyst

(S)-14a (S)-14b (S)-14c

ee(C1Phprod) 62% 74% 0%

ee(C1S(i-Pr)prod) 74% 78% 41%

ee(C2(p-Tol)prod) 38% 31% 26%

ee(C2Meprod) 70% 59% –11%

ee(C1Ph2prod) 42% 51% ----a

ee(C1S(i-Pr)2prod) 52% 49% ----a

average 56% 57% ----a

a Not determined.

Compared to (S)-14a, the catalyst with the tolyl phosphorus substituents ((S)-14b) gave

higher ee values for the five-membered ring Morita Baylis Hillman products C1Phprod and C1S(i-

Pr)prod (74% and 78% vs. 62% and 74%), paralleling the rate trends. However, the values for the

six-membered ring systems C2Meprod and C2(p-Tol)prod were lower (31% and 59% vs. 38% and

70%). The Rauhut Currier products did not exhibit a well defined trend. One ee value was higher

(C1Ph2prod, 42% vs. 51%) and one was comparable (C1S(i-Pr)2

prod, 52% vs. 49%). The lowest ee

values were obtained for the catalyst with the p-C6H4OCH3 phosphorus substituents ((S)-14c).


Although this catalyst gave the fastest reactions (but not the highest yields), the ee values were very

random for the five-membered rings as well as for the six-membered systems; curiously, with

C2Me the opposite enantiomer dominated. The enantiopure catalyst (S)-14d was not employed

because of the low product yields and selectivities.

2.3.1.3 Preparative Experiments

All data presented above were obtained from reactions with very small amounts of

substrates (ca. 0.0050-0.010 g) and catalysts as well. Many reactions were carried out in NMR tubes;

the yields were directly calculated from 1H NMR spectra. Such measurements give an idea about

the reaction rates but different yields are often obtained for the purified products. To show that for

the reactions given above pure products can be obtained in significant yields, some reactions were

carried out in larger scales and worked up to give pure products. The NMR yields and the

preparative experiments are compared in Tables 2.5 and 2.6.

The preparative yields were sometimes significantly lower than those obtained from 1H

NMR experiments. Additionally, it was shown that these products are not complete stable on silica

gel, as TLC spots smear from the baseline. In any case, good to excellent yields were obtained with

C6H6 as solvent. This was in large part due to the avoidance of column chromatography. Instead, a

type of silica gel filtration was employed, as detailed in section 2.5.4.


mol% of 14a in C6H6.

Substrate

C1Ph C1S(i-Pr) C2(p-Tol) C2Me C1Ph2 C1S(i-Pr)2

Yield (1H NMR) 95% 91%b (56%a) 99% 90% 92% (87% a) 98%

Yield (prep.) 91% 99% (53%a) 91% 86% 87% (70% a) 82%

a Obtained in PhCl. b This value may be overstated due to the poor signal to noise ratio and

resolution.



mol% of 14c in PhCl.

Substrate

C1Ph C1S(i-Pr) C2(p-Tol) C2Me C1Ph2

Yield (1H NMR) 61% 70% 51% 84% 71%

Yield (prep.) 55% 58% 40% 54% 50%


2.3.2 Discussion

Because of the good results that were obtained with catalyst 14a, further optimization of this

lead structure was sought. Therefore, the nucleophilicity of the active phosphorus center was

enhanced. Mayr has shown that the nucleophilicities of tertiary aryl phosphines strongly depend on

the substituents in the para position.67 In Table 2.7 the nucleophilicity factors (N) of some tertiary

aryl phosphines are summarized. Higher values correspond to greater nucleophilicities.

Table 2.7. Nucleophilicity factors (N) depending on para substituents (R) of aryl phosphines

reported by Mayr.

As a chlorine substituent withdraws electrons from the ring system (–i effect), the

nucleophilicity is decreased. On the other hand, a strong +i effect effects higher electron density,

and higher nucleophilicity is obtained (CH3). This is superceded upon the introduction of OCH3

and N(CH3)2 substituents, which donate even more electron density to the aromatic systems by

their +m effects. The nucleophilicity of the phosphorus center is raised (OCH3 < N(CH3)2). All of

these trends should be paralleled in the nucleophilicities of the rhenium-containing phosphines.

The chemical shifts of 31P{1H} NMR signals do not necessarily correlate with the

nucleophilicity. But if very similar substituted phosphines are compared they can give an idea about

the electron density at the phosphorus atom. To a first approximation, the lower field the chemical

R N

Cl 12.58 H 14.33

CH3 15.44 OCH3 16.17

N(CH3)2 18.39

P

R

R

R


shift, the higher the electron density (higher shielding), leading possibly to increased nucleophilicity.

The rhenium-containing phosphines show the following 31P{1H} NMR shifts for the PR2 moiety:

8.1 (14a, Ph),38 5.8 ppm (14b, p-Tol), 5.1 ppm (14c, p-C6H4OCH3), 2.8 ppm (14d, p-

C6H4N(CH3)2) (see also Table 3.1, Chapter 3). This fits to the catalytic experiments that showed in

principle that 14d is the most reactive complex, followed by 14c, and 14b.

With regard to enantioselectivities, the more nucleophilic catalyst (S)-14c gives distinctly

lower ee values than (S)-14a,b. Although (S)-14b usually gives higher ee values than less

nucleophilic (S)-14a, there are exceptions. In the author's opinion there are no obvious single

parameter rationales for these trends, which must be regarded as empirical. In general, the Morita

Baylis Hillman and Rauhut Currier reactions are very sensitive to reaction conditions. Accordingly,

the nature or even the identity of the enantiomer-determining step may vary, rendering

systematization more challenging.

Subsequent efforts directed at catalyst optimization involved aryl groups that did not contain

heteroatoms, as described in the next section.


2.4 Second Series of Improved Catalysts

2.4.1 Results

2.4.1.1 Increased Steric Demand at the Catalytic Center

As the first series of improved catalysts showed good reactivity, and furthermore in the case

of 14b increased ee values for the five-membered ring systems, the possibility of increased steric

demand and electron delocalization at the catalytic center was considered. The enhanced electron

delocalization should not be provided by heteroatoms but by extension of the phenyl π-systems. It

was decided to synthesize two new rhenium-containing phosphines, one with two α-naphthyl and

one with two 2-biphenyl moieties (Figure 2.24).

Figure 2.24. New rhenium-containing phosphines 14e,f.

The syntheses were analogous to those of the other rhenium-containing phosphines and are

detailed in Chapter 3. When several representative substrates were treated with 14e in C6H6, no

reactions were observed. Even after several days no conversion was apparent. On the other hand the

catalyst with the naphthyl moieties (14f) showed very slow reactions with C1Ph and C1S(i-Pr),

nearly no reactivity towards C1Ph2, and no reactivity towards all other tested substrates (C1Me2,

C2(p-Tol)2, C1S(i-Pr)2, C2(p-Tol), and C2Me). The reaction profiles for C1Ph (■) and C1S(i-Pr)

(▲) with 14f (10 mol%) in C6H6 are depicted in Figure 2.25.

ON PPh3Re

CH2PR2

R = e, 2-biphen

f, α-naph

14



14f in C6H6. The conversion of 14f to other species in the former reaction is given by the orange

trace (*).

The reactivity of catalyst 14f compared to 14a-d was very low. The complete consumption

of C1Ph took ca. 168 h, but at least conversion to product was high (90%, 1H NMR).

Approximately one third of the catalyst was consumed during this time, as shown by the orange

trace (*) in Figure 2.25. To calculate these values, the 1H NMR signals of the cyclopentadienyl

ligands of the active (s, 5.07 ppm) and the consumed catalyst (s, 5.85 ppm) were integrated (other

cyclopentadienyl signals were not detected). A catalyst solution without any substrate showed no

conversion after 24 h. Also other solutions with unconverted substrates showed only slight catalyst

loss (for example, the C1Me2 mixture showed ca. 8% consumed catalyst after 168 h). The

converted catalyst is assumed to be phosphine oxide, as a sample of 14f was kept under oxygen and

showed the same NMR signals as the consumed catalyst. Additionally, these chemical shifts trend

parallel those reported for the 14a and oxidized 14a (O=14a) analogs, which have been completely

characterized.61

For substrate C1S(i-Pr) catalyst 14f showed low reactivity. However, a NMR yield of 40%

0 20 40 60 80 100 120 140 160 1800

20

40

60

80

0

20

40

60

80

Con

verte

d C

atal

yst (

%)

Pro

duct

Yie

ld (%

)

Time (h)

C1Ph

C1S(i-Pr)


was reached after 166 h. The reaction was then terminated. Phosphine oxide was again apparent but

is not charted.

Because of the low reactivity of 14f, no enantioselective catalysis was attempted. Other

substituents at the nucleophilic phosphorus atom were sought that could confer higher reactivity and

hopefully increase the enantiomeric excess as well.

2.4.1.2 Introduction of Chirality at the Catalytic Center

A new stereocenter at the nucleophilic phosphorus atom was introduced, as shown for

(SReSP)/(SReRP)-17c,d in Figure 2.26. These are comparable to (SReSP)/(SReRP)-17a,b, but feature

two different aryl substituents, one being a phenyl group and the other a naphthyl residue.

Figure 2.26. New rhenium-containing P-stereogenic phosphines (SReSP)/(SReRP)-17c,d.

The synthesis is again detailed in Chapter 3. Catalysts (SReSP)/(SReRP)-17c and

(SReSP)/(SReRP)-17d were always employed as diastereomeric mixtures. Before the reactions were

started, a small amount of catalyst was assayed by 1H NMR spectroscopy and the diastereomeric

excess (de) was calculated from the integrals of the cyclopentadienyl 1H NMR signals, which gave

different singlets for each diastereomer (sections 3.2.1.3 and 3.4.2). The absolute configurations of

the phosphorus centers were not determined, so in each case one diastereomer is termed

"diastereomer 1" and the other "diastereomer 2". The two diastereomeric mixtures of

(SReSP)/(SReRP)-17c (10 mol%) were tested with substrates C1Ph (■) and C1S(i-Pr) (▲) and the

reactions were again followed by 1H NMR. The results are depicted in Figure 2.27.

ON PPh3Re

CH2PRR'∗

R/R' = c, Ph/α-naph

d, Ph/β-naph

(SReSP)/(SReRP)-17


Figure 2.27. Reaction profiles for the cyclizations of C1Ph (■) and C1S(i-Pr) (▲) with 10 mol% of

(SReSP)/(SReRP)-17c in C6H6.

All reactions were carried out in C6H6 and in the best case the reaction was finished after 24

h (C1Ph, diastereomer 2). The diastereomers of (SReSP)/(SReRP)-17c (diastereomer 1, 94% de vs.

diastereomer 2, –92% de) exhibited significantly different reaction rates. With substrate C1Ph,

diastereomer 1 gave a slower reaction than diastereomer 2 (yields: 28% vs. 52%, 3.5 h; 78% vs.

86%, 24 h). A similar effect was noticed with C1S(i-Pr), where diastereomer 2 was also the more

reactive (yields: 12% vs. 28%, 6.5 h; 76% vs. 83%, 48 h).

A β-naphthyl group is commonly considered less bulky than a α-naphthyl group.68 Thus,

analogous experiments were conducted with the slightly less hindered nucleophile (SReSP)/(SReRP)-

17d. The reaction profiles are depicted in Figure 2.28. The rates were much faster than with

(SReSP)/(SReRP)-17c. The rate differences between the diastereomers (diastereomer 1, 48% de vs.

diastereomer 2, –92% de) were not as large as with (SReSP)/(SReRP)-17c. For C1S(i-Pr) the rates

were nearly identical (yields: 49% vs. 48%, 2.0 h; 75%, 3.5 h, both). However, C1Ph showed some

differences (yields: 57% vs. 33%, 0.5 h; 91% vs. 71%, 2.0 h).

0 10 20 30 40 50 60 700

20

40

60

80P

rodu

ct Y

ield

(%)

Time (h)

C1Ph Dia_1C1Ph Dia_2

C1S(i-Pr) Dia_1

C1S(i-Pr) Dia_2

(SReSP)/(SReRP)-17c:

de(diastereomer 1) = 94%de(diastereomer 2) = −92%


Figure 2.28. Reaction profiles for the cyclizations of C1Ph (■) and C1S(i-Pr) (▲) with 10 mol% of

(SReSP)/(SReRP)-17d in C6H6.


The ee values of the products from Figures 2.27 and 2.28 were determined by HPLC. The

results are detailed in Table 2.8. The ee values with catalyst (SReSP)/(SReRP)-17c were quite

impressive. Diastereomer 2 (–92% de) gave the products C1Phprod and C1S(i-Pr)prod with ee

values of 85% and 88%. The ee value for diastereomer 1 was also good, with 82% for C1S(i-Pr).

Only the value for C1Phprod (53%) was moderate, the lowest value within this set of experiments.

In the case of the sterically less demanding β-naphthyl moiety, ee values ranging from 61% to 71%

were obtained. However, these were comparable to the results with 14a (Table 2.2).

0 5 10 15 200

20

40

60

80P

rodu

ct Y

ield

(%)

Time (h)

C1Ph Dia_1C1Ph Dia_2

C1S(i-Pr) Dia_1

C1S(i-Pr) Dia_2

(SReSP)/(SReRP)-17d:

de(diastereomer 1) = 48%de(diastereomer 2) = −92%


Table 2.8. Product ee values for reactions of C1Ph and C1S(i-Pr) with 10 mol% of catalysts

(SReSP)/(SReRP)-17c and (SReSP)/(SReRP)-17d in C6H6.

Catalyst

(SReSP)/(SReRP)-17c (SReSP)/(SReRP)-17d

diastereomer 1a diastereomer 2b diastereomer 1c diastereomer 2d

ee(C1Phprod) 53% 85% 64% 61%

ee(C1S(i-Pr)prod) 82% 88% 72% 71%

a 94% de. b –92% de. c 48% de. d –92% de.


2.4.2 Discussion

2.4.2.1 Discussion of the Second Series Improved Catalysts

The experiments in this section show that the aryl substituents on the "lead structure" 14a

can be made so bulky that catalytic activity ceases. This extreme is represented by the ortho

substituted phenyl groups (2-biphen) in 14e. When the 2-biphenyl groups are replaced by α-

naphthyl groups (14f), activity is restored. Nonetheless, the rates are sluggish compared to 14a-c.

Given these results, it seemed sensible to "back off" on the steric demand a little bit by

substituting one α-naphthyl moiety by a phenyl ring (17c).68 Indeed, both diastereomers of

(SReSP)/(SReRP)-17c proved to be effective catalysts. Diastereomer 2 exhibited enhanced reactivity

compared to the opposite diastereomer 1. However, as detailed in section 3.2.3.1, it has not yet

proved possible to crystallographically characterize one of these diastereomers or a derivative.

Hence, the phosphorus configurations remain unassigned.

More interesting is the fact that the faster reactions with diastereomer 2 give also higher

enantioselectivities (Figure 2.27 and Table 2.8). This is a pleasant circumstance, as this implies that

the diastereomers don't necessarily have to be separated before use as catalysts. Although this

experiment was not carried out, the enantioselectivities derived from a 50:50 diastereomer mixture

would be expected to be comparable to those of the pure diastereomer 2. In any case, the obtained

ee values are to the author's knowledge the highest ever attained for Morita Baylis Hillman

reactions with a monofunctional phosphine catalysts and without co-catalytic additives.

The β-naphthyl-substituted catalyst (SReSP)/(SReRP)-17d did not give any significant

increase of ee values compared to 14a. Moreover, even the reaction rates were lower. Hence, this

catalyst system is not cost- or labor-effective, given the complexity of the synthesis and

diastereomer separation (section 3.2.1.3). But in any case both (SReSP)/(SReRP)-17d and

(SReSP)/(SReRP)-17c are "working systems" that likely can be further optimized with additional

substituents or by employing other types of aryl groups. One interesting direction would involve

anthracenyl homologs, such as depicted in Scheme 2.5 (top).


Scheme 2.5. Possible future directions for catalysts based upon rhenium-containing phosphines.

2.4.2.2 Short Summary and Outlook

Intramolecular versions of the Morita Baylis Hillman and Rauhut Currier reactions have

been investigated. For this, numerous substrates were synthesized. Some of them were new and

some were already reported in the literature. All are capable of giving five- or six-membered ring

systems that are highly functionalized.

Catalytic amounts of rhenium-containing phosphines were employed to promote the

cyclizations. Most of these phosphines were new, although some had already been reported in the

Gladysz group. Reactions were generally screened by NMR or GC. However, it was shown that

significant yields could be obtained in preparative experiments. The solvent, temperature, and

catalysts have been systematically optimized. Reaction rates were found to be a strong function of

the electron densities at the nucleophilic phosphorus centers. The enantioselectivities did not

P

OH HO

SPINOL

ON PPh3Re

P

Ph

ON PPh3Re


correlate with nucleophilicities or steric bulk, but could fine tuned by varying the sizes of the

phosphorus substituents.

Given this successful demonstration that this family of rhenium-containing phosphines can

be very good catalysts for the above mentioned reactions, there remains much room for future

developments. These might include new catalysts derived from novel cyclic diaryl phosphines, such

as the spiro system in Scheme 2.5 (bottom). This sequence would make use of the diol SPINOL,69

and would embed the nucleophilic phosphorus in a fixed conformational environment, possibly

leading to higher reactivities and selectivities.


2.5 Experimental

2.5.1 General Data

All reactions were conducted under N2. NMR spectra were recorded at ambient probe

temperature on Bruker 300 and 400 MHz FT spectrometers and referenced to the residual solvent

signal (1H: CHCl3, 7.26 ppm; 13C{1H}: CDCl3, 77.0 ppm). IR spectra were recorded on an ASI

React IR®-1000 spectrometer. High performance liquid chromatography (HPLC) analyses were

conducted with a ThermoQuest instrument package (pump/autosampler/detector

P4000/AS3000/UV6000LP; Columns: Chiralcel OD, Chiralpak AD-H, Chiralpak AS-H, 250 × 4.6

each, Daicel). Gas chromatography (GC) was conducted with a ThermoQuest Trace GC 2000

instrument (FID; OPTIMA-5 0.25 μm capillary column, 25 m × 0.32 mm). Elemental analyses were

determined with a Carlo Erba EA1110 CHN instrument.

Solvents were treated as follows: n-pentane (Grüssing), distilled from sodium

/benzophenone; C6H6 (Grüssing), distilled from CaH2; CH3CN (Grüssing), CH2ClCH2Cl and PhCl

(2 × Fluka), distilled from P2O5 and stored over molecular sieves (A4); t-BuOH (Grüssing),

distilled from Mg; n-pentane (Grüssing), ethyl acetate, and hexanes (2 × Staub) for column

chromatography, simple distilled; isopropanol (Roth) and hexanes (Fischer) for HPLC, used

without purification; CDCl3 (99.8%, Deutero GmbH), stored over molecular sieves (A4).

Chemicals were treated as follows: Decane (99+%), PPh3 (99%, 2 × Acros), and t-BuOK

(98+%, Acros), used as received.

TLC was carried out with ALUGRAM® SIL G/UV254 plates (Macherey-Nagel). Column

chromatography was conducted using silica gel 60M (Macherey-Nagel). Celite® 535 (Fluka), used

as received.


2.5.2 General Procedures

Procedure A: Reactions that were monitored by GC.

A GC autosampler vial (2 mL) was charged with the substrate and flushed with N2. A

solution of the catalyst was added to the substrate. The resulting solution was stirred and aliquots

(0.050 mL) were regularly assayed by GC. For this, the solvent was removed from the aliquot and

an ethyl acetate solution of decane (standard, 0.000500 M) was added.

Procedure B: Reactions that were monitored by NMR.

A Schlenk flask was charged with the substrate and flushed with N2. Then a 0.0125 M

solution of CH2ClCH2Cl (reference for 1H NMR integration) in the reaction solvent was added to

give a 0.100 M substrate solution. An equal volume of a solution that was 0.0100 M in catalyst and

0.0125 M in CH2ClCH2Cl, corresponding to 10 mol% loading, was added dropwise to the stirred

substrate solution. The mixture or an aliquot thereof was then transferred to a NMR tube, and 1H

NMR spectra were periodically recorded. The product yields and substrate conversions were

calculated from integrations of the CH2ClCH2Cl standard and characteristic substrate/product peaks

(product yield: C=CH and/or CHOH; substrate conversion: CHO).

Procedure C: Reactions to determine enantioselectivity by HPLC.

A reaction mixture was prepared in the same way as procedure B but with

enantiopure/diastereoenriched catalyst. After completion of the reaction, five volumes of hexanes

were added with stirring. The mixture was filtered through a plug of silica gel, which was rinsed

with ethyl acetate/hexanes (1:4 v/v). The solvent was removed from the filtrate and the product

purity was assayed by 1H NMR. The ee was determined by chiral HPLC (isopropanol/hexanes).

Procedure D: Reactions conducted with [catalyst-H]+ PF6– salts.

A Schlenk flask was charged with [catalyst-H]+ PF6– and C6H6. Then t-BuOK (2 equiv.)

was added with stirring. After 30 min, the mixture was filtered through a plug of Celite®, which


was rinsed with C6H6. The filtrate was concentrated and dry n-pentane was added with stirring. A

red solid precipitated, which was isolated by filtration and dried by oil pump vacuum.

A 0.0125 M solution of CH2ClCH2Cl (reference for 1H NMR integration) in the reaction

solvent was added to the red solid to give a 0.0100 M catalyst solution. This solution was added

dropwise with stirring to an equal volume of substrate solution in the same solvent that was also

0.0125 M in CH2ClCH2Cl. The mixture was then transferred to a NMR tube, and 1H NMR spectra

were periodically recorded. The formation of product was determined as indicated in procedure B.

Procedure E: Preparative Experiments

A Schlenk flask was charged with the substrate (typically 0.100-0.150 g) and flushed with

N2. Then a 0.0125 M solution of CH2ClCH2Cl (reference for 1H NMR integration) in the reaction

solvent was added to give a 0.100 M substrate solution. This was equilibrated to 20 °C using a

cryostat. An equal volume of a solution that was 0.0100 M in catalyst and 0.0125 M in

CH2ClCH2Cl, corresponding to 10 mol% of catalyst, was cooled to 0 °C and added dropwise over a

period of 5 min. An aliquot (0.6 mL) was transferred to a NMR tube, and 1H NMR spectra were

periodically recorded. When the reaction was complete (or no subsequent reaction took place), five

volumes of hexanes were added with stirring. The mixture was filtered through a plug of silica gel,

and the plug was rinsed (1:4 v/v ethyl acetate/hexanes). The solvent was removed from the filtrate

by rotary evaporation. Reactions conducted in C6H6 gave satisfactory product purity. Reactions

conducted in PhCl were purified by column chromatography (SiO2; solvents are indicated below).

The product C1Ph2prod, which was obtained from reaction in PhCl, was not purified by column

chromatography, but contained small quantities of PhCl.

Reference NMR spectra for products CnRprod and CnR2prod. Procedures B, D, and E

involved monitoring by 1H NMR. These used peaks from products previously reported in the

literature (C1Phprod,25 C1(p-Tol)prod,43 C1Meprod,28 C1OEtprod,25 C1Ph2prod,19,20,26

C1Me2prod,26,60 C2Meprod,70 and C2OEtprod 25) or isolated in section 2.5.4 (C1S(i-Pr)prod,

C1S(i-Pr)2prod, and C2(p-Tol)prod).


2.5.3 Analytic Experiments Listed by Figures

Reaction of C1Ph with 10 mol% of 14a38 in different solvents (Figure 2.5). Substrate C1Ph

(0.0048 g, 0.025 mmol), catalyst 14a (0.0019 g, 0.0025 mmol) and solvent (0.50 mL) were

combined as in procedure A.

The GC monitoring for solvent CH3CN gave the following data:

Time (h) Yield (%)

0 0 24 28 72 42 144 46 192 51

The GC monitoring for solvent CH2ClCH2Cl gave the following data:

Time (h) Yield (%)

0 0 3.0 59 19 75 49 80 50 82 119 95 144 95

The GC monitoring for solvent mixture CH2ClCH2Cl/t-BuOH (1:1 v/v) gave the following data:

Time (h) Yield (%)

0 0 2.0 18 22 27 96 29


Reaction of C1Ph with 10 mol% of PPh3 in CH2ClCH2Cl (Figure 2.5). Substrate C1Ph (0.0048

g, 0.025 mmol), catalyst PPh3 (0.00070 g, 0.0025 mmol) and CH2ClCH2Cl (0.50 mL) were

combined as in procedure A. The GC monitoring gave the following data:

Time (h) Yield (%)

0 0 24 5 72 13 96 16 120 17 144 21 168 24 192 24

Reaction of C1Ph with 10 mol% of 14a in different solvents (Figure 2.5). Substrate C1Ph

(0.0048 g, 0.025 mmol), catalyst 14a (0.0019 g, 0.0025 mmol) and solvent (0.50 mL) were

combined as in procedure B.

The GC monitoring for solvent PhCl gave the following data:

Time (h) Yield (%)

0 0 0.4 60 2.0 90

The GC monitoring for solvent C6H6 gave the following data:

Time (h) Yield (%)

0 0 0.25 50 0.75 95 1.3 95


Reaction of C1Ph with 10 mol% of 14a in CH3CN at 0 °C (Figure 2.6). Substrate C1Ph (0.0048

g, 0.025 mmol), catalyst 14a (0.0019 g, 0.0025 mmol) and CH3CN (0.50 mL) were combined as in

procedure A, but the catalyst and substrate solutions were precooled to 0 °C. The reaction mixture

was kept at 0 °C for the entire experiment. The GC monitoring gave the following data:

Time (h) Yield (%)

0 0 1.2 13 24.7 25 30.7 25 40.8 25 54.7 25

Reaction of C1Ph with 10 mol% of 14a in CH2ClCH2Cl at 40 °C (Figure 2.7). Substrate C1Ph

(0.0048 g, 0.025 mmol), catalyst 14a (0.0019 g, 0.0025 mmol) and CH2ClCH2Cl (0.50 mL) were

combined as in procedure A, but the catalyst and substrate solutions were prewarmed to 40 °C. The

reaction mixture was kept at 40 °C for the entire experiment. The GC monitoring gave the

following data:

Time (h) Yield (%)

0 0 24 18 48 19 72 18 96 20 120 22 143 23

Reaction of C1Ph with 10 mol% of 14a in PhCl with a temperature gradient from –20 °C to

room temperature (text section 2.2.1.3). Substrate C1Ph (0.014 g, 0.074 mmol), catalyst 14a

(0.0055 g, 0.0074 mmol), and PhCl (1.5 mL) were combined as in procedure B, but the catalyst and

substrate solutions were precooled to –20 °C (ice/NaCl). The reaction solution was allowed to

slowly warm to room temperature within 12 h. A 1H NMR spectrum of an aliquot showed that the


substrate was consumed, but only side products were detected.

Reaction of various substrates with 10 mol% of 14a in PhCl (Figure 2.9). Substrate C1(p-Tol),

C2(p-Tol), C1Me, C1S(i-Pr), C1Ph2, C2Me, or C1S(i-Pr)2 (typically 0.0080-0.010 g), catalyst 14a,

and PhCl (typically 0.70-1.5 mL) were combined as in procedure B. The NMR monitoring gave the

following data:

Yield (%)

Time (h) C1(p-Tol)prod C2(p-Tol)prod C1Meprod 0 0 0 0 1 73 5 10 3 95 11 27 18 62 83 22 68 86 25 72 85 44 88 86 48 88 88 114 93

Yield (%) Yield (%)

Time (h) C1Ph2prod Time (h) C1S(i-Pr)prod

0 0 0 0 0.33 43 0.25 0 1.0 63 0.5 7 1.8 87 3.0 14 3.0 87 6.0 33

10 40 29 50

Reaction of various substrates with 10 mol% of 14a in C6H6 (Figures 2.10 and 2.23). Substrate

C2(p-Tol), C1S(i-Pr), C1Ph2, C2Me, or C1S(i-Pr)2 (typically 0.0080-0.010 g), catalyst 14a, and

C6H6 (typically 0.70-1.5 mL) were combined as in procedure B. The NMR monitoring gave the

following data:


Yield (%) Yield (%)

Time (h) C1S(i-Pr)prod Time (h) C2Meprod 0 0 0 0

1.5 49 1.5 8 3.0 72 2.75 10 4.5 84 4.5 18 5.5 91 6.0 20

24 79 48 90

Yield (%) Yield (%)

Time (h) C1Ph2prod Time (h) C1S(i-Pr)2

prod 0 0 0 0

1.25 69 21 50 1.75 75 46 76 2.75 82 69 86 4.3 89 96 92 5.75 92 120 98

Yield (%) Conversion (%)

Time (h) C2(p-Tol)prod C2(p-Tol) 0 0 0

1.33 10 11 3.0 20 23 4.5 29 30 6.0 33 35 24 74 79 48 89 94 72 99 100

Reaction of various substrates with 10 mol% of (η5-C5H5)Re(NO)(PPh3)(CHRP(Ph)2)

((SReSC)-15a: R = Ph,51 (SReSC)-15b: R = CH3) (Figure 2.12). Substrate C1Ph, C2Me, C2Ph,

C2OEt, or C1OEt (typically 0.0080-0.010 g), catalyst 15a or 15b, and PhCl (typically 0.70-1.5 mL)

were combined as in procedure B. The NMR monitoring gave the following data:


Complex (SReSC)-15a gave no reaction; data for the reaction with (SReSC)-15b (no reaction

occurred with C2Me, C2Ph, C2OEt, or C1OEt):

Yield (%)

Time (h) C1Phprod 0 0 72 65 120 84 168 86 240 88

Reaction of various substrates with 10 mol% of (η5-C5H4PPh2)Re(NO)(PPh3)(CHRP(Ph)2)

((SReSC)-16a: R = Ph,51 (S)-16b: R = H38) (Figure 2.13). Substrate C1Ph, C2Me, C2Ph, C2OEt,

or C1OEt (typically 0.0080-0.010 g), catalyst 16a or 16b, and PhCl (typically 0.70-1.5 mL) were

combined as in procedure B. The NMR monitoring gave the following data:

Complex (SReSC)-16a gave no reaction; data for the reaction with (S)-16b (no reaction occurred

with C2Me, C2Ph, C2OEt, or C1OEt):

Yield (%)

Time (h) C1Phprod 0 0 72 27 120 38 168 41 240 41

Reaction of various substrates with 10 mol% of (η5-C5H5)Re(NO)(PPh3)(CH2PCyR)

((SReSP)/(SReRP)-17a: R = Ph (91% de), (SReSP)/(SReRP)-17b: R = t-Bu (80% de))52 in PhCl

(Figure 2.14). These sequences were begun with protonated catalysts [catalyst-H]+ PF6– (typically

0.040-0.060 g) following procedure D. Substrate C1Ph, C2Me, C2Ph, C2OEt, or C1OEt (typically

0.040-0.060 g), catalyst (SReSP)/(SReRP)-17a or (SReSP)/(SReRP)-17b, and PhCl (typically 1.2-1.9

mL) were then combined as indicated. The NMR monitoring gave the following data:


Complex (SReSP)/(SReRP)-17b gave no reaction; data for the reaction with diastereomeric mixture

(SReSP)/(SReRP)-17a (no reaction occurred with C2Ph, C2OEt, or C1OEt):

Yield (%)

Time (h) C1Phprod C2Meprod 0 0 0 24 90 23 72 50 96 63 168 76 216 78

Reaction of C1Ph with 10 mol% of 14a in PhCl at –25 °C (Figure 2.17). Substrate C1Ph (0.014

g, 0.074 mmol), catalyst 14a (0.0055 g, 0.0074 mmol), and PhCl (1.5 mL) were combined as in

procedure B, but the catalyst and substrate solutions were precooled to –25 °C. The reaction

solution was kept at –25 °C for 12 h. A 1H NMR spectrum of an aliquot showed that the substrate

was consumed. The mixture was chromatographed (SiO2, ethyl acetate/hexanes, 3:7 v/v). Results:

see text.

Reaction of various substrates with 10 mol% of (η5-C5H5)Re(NO)(PPh3)CH2PR2 (R = p-Tol

(14b), p-C6H4OCH3 (14c), p-C6H4N(CH3)2 (14d), α-naph (14f)) in PhCl or C6H6 (Figures 2.22,

2.23, and 2.25, Table 2.3). Substrate C1Ph, C2(p-Tol), C1OEt, C2OEt, C1Me, C2Me, C1Ph2,

C1S(i-Pr)2, C2(p-Tol)2, C1Me2, or C1S(i-Pr) (typically 0.0080-0.010 g), catalyst 14b, 14c, 14d, or

14f, and C6H6 or PhCl (typically 0.70-1.5 mL) were combined as in procedure B. The NMR

monitoring gave the following data:

Data for the reaction with 14b in PhCl:

Yield (%)

Time (h) C1Phprod C2(p-Tol)prod C1OEtprod 0 0 0 0


0.25 24 9 -- 0.75 38 -- -- 22 69 75 10 45 87 80 16 96 26 192 30

Yield (%)

Time (h) C1Meprod C2Meprod C1S(i-Pr)prod 0 0 0 0

0.5 9 0 29 22 58 48 72 48 63 144 63

Data for the reaction with 14c in PhCl:

Yield (%) Yield (%)

Time (h) C1S(i-Pr)prod Time (h) C1Phprod 0 0 0 0

1.5 60 0.17 54 2.75 70 1.5 61 18 70

Yield (%) Yield (%)

Time (h) C2(p-Tol)prod Time (h) C2Meprod 0 0 0 0

0.25 3 0.25 2 1.5 19 1.5 30 3.0 32 3.0 49 6.0 43 4.5 63 10 51 5.75 73 23 50 7.3 83 29 51 26 87

Yield (%) Yield (%)

Time (h) C1OEtprod Time (h) C1Ph2prod

0 0 0 0


22 18 0.25 55 45 28 1.0 64 95 39 1.75 66 192 43 2.9 71

Yield (%)

Time (h) C1Meprod 0 0

0.5 20 22 55

Data for the reaction with 14d in PhCl (monitoring was not feasible due to the complex 1H NMR

spectra; the yields are the highest reached after the given time and could only be estimated):

Product C1Phprod C1Meprod C2OEtprod C2(p-Tol)prod Time (h) 0.5 3.0 48 1.0 Yield (%) 20 20 25 50

Product C2Meprod C1OEtprod C1S(i-Pr)prod Time (h) 48 24 0.5 Yield (%) 55 20 35

Data for the reaction with 14b in C6H6 (no reaction occurred with C2(p-Tol)2):

Yield (%)

Time (h) C1Phprod C1S(i-Pr)prod C2Meprod 0 0 0 0

0.5 97 70 10 2.0 100 90 20 3.5 100 30 6.5 80 24 85


Time (h) C1Ph2prod C1S(i-Pr)2

prod C2(p-Tol)prod C2(p-Tol) 0 0 0 0 0


0.5 70 10 15 18 2.0 70 25 35 48 3.5 75 45 65 70 6.5 75 65 80 91 24 95 85 100

Data for the reaction with 14c in C6H6 (no reaction occurred with C2(p-Tol)2):

Yield (%)

Time (h) C1Phprod C1S(i-Pr)prod C2Meprod 0 0 0 0

0.5 54 64 8.0 2.0 54 90 25 3.5 90 35 6.5 90 48 24 70


Time (h) C1S(i-Pr)2prod C1Ph2

prod C2(p-Tol)prod C2(p-Tol) 0 0 0 0 0

0.5 30 20 17 20 2.0 65 20 48 69 3.5 73 60 84 6.5 73 69 92 24 75 100

Data for the reaction with 14f in C6H6 (no reaction occurred with C2(p-Tol), C2Me, C1Ph2, C1S(i-

Pr)2, C2(p-Tol)2, or C1Me2):

Yield (%) Consumed catalyst (%)a

Time (h) C1Phprod C1S(i-Pr)prod 14f 0 0 0 0

1.5 -- -- 21 7.5 6 -- -- 24 20 5 23 72 50 14 27


168 90 40 35 192 -- -- 35

a calculated from the cyclopentadienyl 1H NMR integrals (section 2.4.1.1).

Reaction of C1Ph and C1S(i-Pr) with 10 mol% of (η5-C5H5)Re(NO)(PPh3)(CH2PPhR)

((SReSP)/(SReRP)-17c: R = α-naph, (SReSP)/(SReRP)-17d: R = β-naph) in C6H6 (Figures 2.27

and 2.28). These sequences were begun with protonated catalysts [catalyst-H]+ PF6– (typically

0.040-0.060 g, de: see tables below) following procedure D. Substrate C1Ph or C1S(i-Pr) (typically

0.0080-0.010 g), the diastereomeric mixture of catalyst (SReSP)/(SReRP)-17c or (SReSP)/(SReRP)-

17d, and C6H6 (typically 0.70-1.5 mL) were then combined as indicated. The NMR monitoring

gave the following data:

Data for the reaction with catalyst (SReSP)/(SReRP)-17c:

Yield (%)

diastereomer 1 de = 94%

diastereomer 2 de = –92%

Time (h) C1Phprod C1S(i-Pr)prod C1Phprod C1S(i-Pr)prod 0 0 0 0 0

0.5 -- -- 11 -- 2.0 16 -- 36 7 3.5 28 5 52 14 6.5 39 12 72 28 24 78 52 86 68 48 86 76 83 72 91

Data for the reaction with catalyst (SReSP)/(SReRP)-17d:

Yield (%)

diastereomer 1 de = 48%

diastereomer 2 de = –92%

Time (h) C1Phprod C1S(i-Pr)prod C1Phprod C1S(i-Pr)prod 0 0 0 0 0

0.5 57 23 33 16


2.0 91 49 71 48 3.5 75 86 75 6.5 87 83 24 88 88

Reactions with enantiopure/diastereomeric catalysts (Tables 2.1, 2.2, 2.4, and 2.8). Procedure C

was applied for several substrates. If reactions using racemic catalysts 14a-c were already

monitored by procedure A or B, the same reaction times were used with enantiopure catalysts ((S)-

14a-c). If the reaction was only monitored with diastereopure/diastereoenriched catalysts ((SReSC)-

15b; (SReSC)-16b; (SReSP)/(SReRP)-17a,c,d), the resulting mixtures were subsequently treated as in

procedure C.

2.5.4 Preparative Reactions

Procedure E was applied. Products were usually characterized by 1H NMR, 13C{1H} NMR,

and IR spectroscopy. If the compound was new, elemental analysis was also determined. The

products were isolated from reactions conducted in PhCl by column chromatography (SiO2;

solvents are indicated below), except the one involving C1Ph2. Yields: see text (Tables 2.5 and 2.6).

Ph(CO)C=CHCH2CH2CHOH (C1Phprod)25 was obtained (7:3 v/v ethyl acetate/n-pentane) as a

slightly yellow oil. Spectroscopic data agreed with that in the literature.

i-PrS(CO)C=CHCH2CH2CHOH (C1S(i-Pr)prod) was obtained (3:2 v/v ethyl acetate/n-pentane)

as a colorless oil. Elemental analysis calcd (%) for C9H14O2S (186.1): C 58.03, H 7.58, S 17.21;

found: C 57.63, H 7.71, S 16.78.

1H NMR (400 MHz, CDCl3, δ in ppm): 6.89 (dd, 3J(H,H) = 4.8 Hz and 2.4 Hz, C=CHCHH',

1H), 5.16-5.13 (m, CHOH, 1H), 3.74 (sep, 3J(H,H) = 7.2 Hz, (CH3)2CH, 1H), 2.78 (br s, CHOH,

1H), 2.73-2.62 (m, CHH'CHOH, 1H), 2.46-2.27 (m, C=CHCHH', CHH'CHOH, 2H), 1.91-1.82 (m,

C=CHCHH', 1H), 1.39 (d, (CH3)2CH, 3J(H,H) = 7.2 Hz, 6H); 13C{1H} NMR (101 MHz, CDCl3, δ

in ppm): 190.1 (s, (CO)C=CH), 145.2 (s, (CO)C=CH), 144.4 (s, (CO)C=CH), 75.7 (s, CHOH), 34.3


(s, (CH3)2CH), 31.8 (s, CH2CHOH), 30.9 (s, C=CHCH2), 23.0 (s, (CH3)2CH).

IR (thin film, cm–1):71 3450 (br, νOH), 1648 (s, νCO), 1613 (s, νC=C).

p-Tol(CO)C=CHCH2CH2CH2CHOH (C2(p-Tol)prod) was obtained (4:1 v/v ethyl acetate/n-

pentane) as a slightly yellow oil. Elemental analysis calcd (%) for C14H16O2 (216.1): C 77.75, H

7.46; found: C 77.18, H 7.53.

1H NMR (400 MHz, CDCl3, δ in ppm): 7.58 (d, 3J(H,H) = 8.2 Hz, C6H4, o to CO, 2H),

7.24 (d, 3J(H,H) = 8.2 Hz, C6H4, m to CO, 2H), 6.70 (t, 3J(H,H) = 3.9 Hz, C=CH, 1H), 4.69-4.72

(m, CHOH, 1H), 3.55 (br s, CHOH, 1H), 2.41 (s, CH3, 3H), 2.42-2.18, 1.97-1.82, 1.69-1.60 (3 m, 3

CHH', 6H); 13C{1H} NMR (101 MHz, CDCl3, δ in ppm): 199.1 (s, (CO)C=CH), 146.2 (s, C6H4, p

to CO), 142.7 (s, (CO)C=CH), 139.9 (s, (CO)C=CH), 135.0 (s, C6H4, i to CO), 129.6, 128.9 (2 s,

C6H4, o, m to CO), 64.2 (s, CHOH), 29.7, 26.3, 17.5 (3 s, 3 CH2), 21.6 (s, CH3).

IR (thin film, cm–1):71 3460 (br, νOH), 1633 (s, νCO), 1606 (s, νC=C).

CH3(CO)C=CHCH2CH2CH2CHOH (C2Meprod)70 was obtained (7:3 v/v ethyl acetate/n-pentane)

as a colorless oil. Spectroscopic data agreed with that in the literature.

Ph(CO)C=CHCH2CH2CHCH2(CO)Ph (C1Ph2prod)19,20,26 was obtained as a brown oil; the 1H

NMR spectrum of the product from PhCl, which was not chromatographed showed a small amount

of residual solvent. Spectroscopic data agreed with that in the literature.

i-PrS(CO)C=CHCH2CH2CHCH2(CO)S(i-Pr) (C1S(i-Pr)2prod) was obtained (1:9 v/v ethyl

acetate/n-pentane) as a tan liquid. Elemental analysis calcd (%) for C14H22O2S2 (286.1): C 58.70,

H 7.74, S 22.39; found: C 58.52, H 7.62, S 22.41.

1H NMR (400 MHz, CDCl3, δ in ppm): 6.81-6.78 (m, (CO)C=CH, 1H), 3.72 (sep, 3J(H,H)

= 7.0 Hz, (CH3)2CH, 1H), 3.67 (sep, 3J(H,H) = 7.0 Hz, CH(CH3)2', 1H), 3.53-3.44 (m,

CHH'CHH'CH, 1H), 3.08 (dd, 2J(H,H) = 15.2 Hz, 3J(H,H) = 3.3 Hz, CHH'(CO), 1H), 2.48 (dd,

2J(H,H) = 15.2 Hz, 3J(H,H) = 10.2 Hz, CHH'(CO), 1H), 2.60-2.41 (m, CHH'CHH'CH, 2H), 2.25-

2.15, 1.84-1.76 (2 m, CHH'CHH'CH, 2H), 1.32 (d, 3J(H,H) = 7.0 Hz, (CH3)2CH, 6H), 1.29 (d,

76 2 Catalysis with Rhenium-Containing Phosphines 3J(H,H) = 7.0 Hz, CH(CH3)2', 6H); 13C{1H} NMR (101 MHz, CDCl3, δ in ppm): 198.3 (s,

CH2(CO)), 188.8 (s, (CO)C=CH), 146.7 (s, (CO)C=CH), 143.1 (s, (CO)C=CH), 47.8 (s, CH2(CO)),

42.0 (s, CH2CH2CH), 34.5, 34.3 (2 s, (CH3)2CH and CH(CH3)2'), 31.6 (s, CH2CH2CH), 29.1 (s,

CH2CH2CH), 23.15, 22.97, 22.94, 22.91 (4 s, (CH3)(CH3)'CH and (CH(CH3)(CH3)')').

IR (thin film, cm–1):71 1683 (s, νCO), 1652 (s, νCO), 1613 (s, νC=C).

2.5.5 Isolation of Side Product C=CHCH2CH2CHCH2C(CH3)(OH)CH2(CO) (19)

Procedure E was applied to substrate C1Me2 (0.027 g, 0.162 mmol) and catalyst 14b

(0.0125 g, 0.0162 mmol) in PhCl (3.2 mL). However, 1H NMR spectra were not periodically

recorded. After 72 h, an equivalent volume of hexanes was added with stirring. The mixture was

filtered through a plug of silica gel, and the plug was rinsed (1:1 v/v ethyl acetate/hexanes). The

solvent was removed from the filtrate by rotary evaporation. The crude product was purified by

column chromatography (4:1 v/v ethyl acetate/n-pentane). First, a mixture of C1Me2prod and 20

was obtained. The spectroscopic data for each agreed with that in the literature.26,60 Second, a

subsequent fraction gave pure 19, the structure of which was established by 1H NMR and 13C{1H}

NMR.

Data for 19: 1H NMR (400 MHz, CDCl3, δ in ppm): 6.64-6.59 (m, C=CHCH2, 1H), 3.36-

3.23 (m, CH2CH, 1H), 2.52 (d, 2J(H,H) = 17.2 Hz, CHH'CO, 1H), 2.48-2.38 (m, C=CHCH2, 2H),

2.34 (d, 2J(H,H) = 17.2 Hz, CHH'CO, 1H), 2.34-2.25 (m, CHH'CH, 1H), 2.17-2.08 (m, CHH'CH,

1H), 1.92 (br s, OH, 1H), 1.61-1.49 (m, CHCHH'COH, 1H), 1.42 (apparent t, 2J(H,H) = 3J(H,H) =

12.8 Hz, CHCHH'COH, 1H), 1.35 (s, CH3, 3H); 13C{1H} NMR (101 MHz, CDCl3, δ in ppm):

198.2 (s, CH2(CO)), 143.8 (s, C=CH), 138.4 (s, C=CH), 73.0 (s, CH2COH), 53.6 (s, CH2(CO)),

44.0 (s, CH2COH), 40.8 (s, CHCH2CH2), 33.0, 32.0 (2 s, CHCH2CH2), 31.0 (s, CH3).

3

Rhenium-Containing Phosphines

3.1 Introduction to Rhenium Complexes

There are ca. 18000 publications dealing with manganese complexes. On the other hand, for

the homologous element rhenium there are currently ca. 2000 publications on the subject of

rhenium complexes, as a simple SciFinder® search shows. This is in one sense astonishing, because

from the author's experience, rhenium forms stable organometallic compounds quite easily.

However, rhenium is a rare metal (although it is no rare earth metal), and as compared to others is

quite expensive. Complexes are often crystalline, which facilitates purification and handling.72,73

In the Gladysz group many rhenium complexes have been developed within the last 30

years. Most isolable species are inert against oxygen and moisture. The typical core fragment from

which most of these complexes are derived was shown in Figure 2.1 (Structure B).

In principle the cyclopentadienyl ligand can be modified by lithiation, the PPh3 ligand can

be substituted by phosphine derivatives, and the moiety X can be an alkyl group, a phosphine, an

amine, or something similar.

As reviewed in Chapter 1, phosphines and amines are very useful compounds in

organocatalytic reactions.1,5-10 During recent decades numerous rhenium-containing

phosphines31,33,36-38,41,51,74 and amines75-79 have been developed in the Gladysz group, many of

which were employed as ligands in transition metal catalysis.36-39,41,74 Some of these phosphines

were shown in free form (4-6), or already coordinated to transition metals (7-13) in Figures 2.3 and

2.4.

Several analogous phosphine oxides were also prepared.31,52,61,80,81 These were evaluated

as catalysts for allylation reactions. Unfortunately, the yields as well as the enantiomeric excesses

were very low.61,81 Hence, only the preparation of the complexes has been published.

However, some of the rhenium-containing phosphines were successful as catalysts in

78 3 Preparation of Rhenium-Containing Phosphines

intramolecular Morita Baylis Hillman and Rauhut Currier reactions. Accordingly, improved

second-generation catalysts were sought, and were developed as described in this chapter.

All of these were prepared by established procedures. These are very fundamental for this

project and are therefore sketched in the following introduction.

The synthesis of the basic building block starts with commercially available Re2(CO)10,

which is converted in three steps to the racemic carbonyl complex [(η5-C5H5)Re(NO)(PPh3)(CO)]+

BF4–. This is stable for an indefinite time period under ambient laboratory conditions.82 Indeed,

most complexes that are mentioned in this chapter are eighteen valence electron species that exhibit

excellent chemical and configurational stability.

The racemic salt [(η5-C5H5)Re(NO)(PPh3)(CO)]+ BF4– plays a central role. The rhenium

atom is a stereocenter and the racemate can be resolved into enantiomers via a four step procedure.

The (S) or (R) stereoisomer is subsequently treated in the same way as the racemic complex.

Reaction with NaBH4 leads to a reduction of the carbonyl group to give the neutral methyl complex

(η5-C5H5)Re(NO)(PPh3)(CH3) (26) in either enantiopure or racemic form, depending upon the

educt.82 Starting from this basic building block, numerous conversions are possible, and relevant

literature reactions are summarized in Scheme 3.1.

The abstraction of a hydride by Ph3C+ PF6– to give the methylidene species [(η5-

C5H5)Re(NO)(PPh3)(=CH2)]+ PF6– is an important process.83 Usually this cation is formed in situ,

but it can also be isolated.83 This species easily reacts with a variety of nucleophiles, including

PPh2H. Subsequent deprotonation of the resulting phosphonium salt leads to the free phosphine

(η5-C5H5)Re(NO)(PPh3)(CH2PPh2) (14a). Finally, lithiation using n-BuLi followed by a

nucleophilic substitution on PPh2Cl gives the diphosphine (η5-C5H4PPh2)Re(NO)(PPh3)(CH2PPh2)

(16b).38

Another conversion can be carried out involving functionalization of the methylene spacer

to provide one more stereocenter at the carbon atom (15a, 16a). First, the methylidene species is

formed by the addition of Ph3C+ PF6–. Subsequent reaction with PhLi affords the benzyl complex

(η5-C5H4PPh2)Re(NO)(PPh3)(CH2Ph).

3 Preparation of Rhenium-Containing Phosphines 79

Scheme 3.1. Syntheses of rhenium-containing phosphines with chiral centers. Enantioselective (and

diastereoselective) syntheses are possible in each case. a) Ph3C+ PF6–, CH2Cl2. b) PPh2H. c) t-

BuOK, THF. d) n-BuLi, THF. e) PPh2Cl. f) PhLi. g) t-BuLi. h) HBF4.OEt2, PhCl.

ON PPh3Re

CH2

ON PPh3Re

PPh2

ON PPh3Re

CH2PPh2

ON PPh3Re

CHPhPPh2

ON PPh3Re

CH2PPh2

ON PPh3Re

PPh2

Li Li

ON PPh3Re

CHPhPPh2

PPh2

b) c)

d)

f)a)b)c)

g)

b)

c)

d)

1814a

15a

16a

ON PPh3Re

CH3

(S)-26 or

racemate

h)

PF6

BF4

ON PPh3Re

ON PPh3Re

CH2PPh2

PPh2

16b

e) e)

ON PPh3Re

PPh2

PPh2

27

(PhCl)

a)

ON PPh3Re

CHPhPPh2

Li

e)


A hydride is similarly removed from the benzyl complex, leading to the benzylidene

complex [(η5-C5H4PPh2)Re(NO)(PPh3)(=CHPh)]+ PF6–.84 As detailed in earlier papers, the

benzylidene complex can exist as two geometric isomers, and either can be obtained depending on

the temperature at which the reaction is carried out. Subsequently, the benzylidene complex is

stereospecifically attacked by the nucleophile PPh2H and after deprotonation only one diastereomer

of the phenyl-substituted phosphine species (η5-C5H5)Re(NO)(PPh3)(CHPhPPh2) (15a) is obtained.

15a can be subsequently converted to the diphosphine (η5-C5H4PPh2)Re(NO)(PPh3)(CHPhPPh2)

(16a) by lithiation and reaction with PPh2Cl.51

A third important sequence is initiated by treating 26 with a strong Brønsted acid such as

HBF4.OEt2 in PhCl. After the evolution of CH4, the cationic rhenium species [(η5-

C5H5)Re(NO)(PPh3)(PhCl)]+ BF4– is formed in situ, in which a very labile solvent molecule (PhCl)

is σ/π coordinated. This is treated with the nucleophile PPh2H and then base to give the free

phosphine (η5-C5H5)Re(NO)(PPh3)(PPh2) (18). This is converted, similarly to 14a and 15a, to the

diphosphine (η5-C5H4PPh2)Re(NO)(PPh3)(PPh2) (27).38

Using reactions of the type in Scheme 3.1, many rhenium-containing phosphines have been

developed and some of them were already mentioned in Chapter 2. All of the above steps can be

carried out on multigram scales with very good yields. Additionally, there is full retention of

configuration at the rhenium center.85,86 Hence, any useful enantioselective catalysts can likely be

synthesized on very large scales.


3.2 Results

3.2.1 Preparation of Rhenium Complexes

3.2.1.1 Preparation of Racemic Rhenium-Containing Phosphines

It was sought to extend the previously reported syntheses of the rhenium-containing

phosphines 14a, 15a, and 16a,b to related complexes, and evaluate their catalytic activity. The

preparation of protonated analogs of 14a is depicted in Scheme 3.2.

Scheme 3.2. Preparation of the protonated racemic rhenium-containing phosphines [14-H]+ PF6–. a)

Ph3C+ PF6– (1.1 equiv.), CH2Cl2. b) PR2H.

Starting with the well known racemic methyl complex 26,82 a slight excess of the strong

hydride abstracting reagent Ph3C+ PF6– was added at –78 °C. The methylidene complex [(η5-

C5H5)Re(NO)(PPh3)(=CH2)]+ PF6– formed in situ and was subsequently treated with a

symmetrically substituted secondary phosphine PR2H (R = p-Tol (28b), p-C6H4OCH3 (28c),87 p-

C6H4N(CH3)2 (28d),87 2-biphen (28e), α-naph (28f);88 for the preparation of the secondary

phosphines see section 3.2.2). After the mixture was allowed to warm to room temperature, the

ON PPh3Re

CH3

ON PPh3Re

CH2PR2H

PF6

[14b-H]+ PF6−: R = p-Tol, 94%

[14c-H]+ PF6−: R = p-C6H4OCH3, 88%

[14d-H]+ PF6−: R = p-C6H4N(CH3)2, 93%

[14e-H]+ PF6−: R = 2-biphen, 95%

[14f-H]+ PF6−: R = α-naph, 87%

a)

b)

[14-H]+ PF6−26


protonated rhenium-containing phosphines [(η5-C5H5)Re(NO)(PPh3)(CH2PR2H)]+ PF6– ([14-H]+

PF6–) precipitated with the addition of n-pentane. The products were obtained in very good yields

as orange to red powders (R = p-Tol ([14b-H]+ PF6–), 94%; p-C6H4OCH3 ([14c-H]+ PF6

–), 88%;

p-C6H4N(CH3)2 ([14d-H]+ PF6–), 93%; 2-biphen ([14e-H]+ PF6

–), 95%; α-naph ([14f-H]+ PF6–),

87%). If impurities were found, recrystallization from CH2Cl2/n-pentane was possible at any time.

All complexes were characterized by elemental analysis, NMR (1H, 13C{1H}, 31P{1H}) and IR

spectroscopy, and mass spectrometry. Melting points were also recorded, but most were in fact

decomposition points, as indicated by a darkening of color before or while melting.

The two phosphorus substituents R in [14-H]+ PF6– are diastereotopic, and therefore two

sets of NMR signals were obtained. The substituents R rotate around the phosphorus-carbon bonds

quite fast on the NMR time scale at room temperature. Therefore, for [14(b-d)-H]+ PF6– a set of

four signals for each phenyl ring was observed in the 13C{1H} NMR spectra. Most of them were

31P coupled doublets.

For complexes [14e,f-H]+ PF6–, in which the R groups are less symmetric, the 13C{1H}

NMR spectra were considerably more complicated. It was not possible to reliably differentiate

between singlets and 31P coupled doublets. However, there is no evidence from the pattern of the

signals of hindered rotation or other dynamic behavior.

Next, [14-H]+ PF6– were deprotonated as depicted in Scheme 3.3. This transformation is a

simple acid-base reaction that was carried out in the nonpolar solvent C6H6. As [14-H]+ PF6– are

highly polar salts, they are almost insoluble in C6H6. The t-BuOK can be supposed to be insoluble

also. Thus, after the addition of the reactants a heterogeneous mixture was obtained and with

vigorous stirring the deprotonation took place. Most of the rhenium-containing free phosphines are

highly soluble in C6H6 and therefore red suspensions containing the white salt K+ PF6– were

obtained. This salt was removed by filtration through a small plug of Celite®. As the filtrate

contained some t-BuOH, which could inhibit catalysis as mentioned in section 2.2.2.1, n-pentane

was added to precipitate the products. The deprotonated phosphines (η5-

C5H5)Re(NO)(PPh3)(CH2PR2) (14) were obtained in good yields as orange to red solids (14b, 80%;

14c, 77%; 14d, 85%; 14e, 91%; 14f, 64%).


Scheme 3.3. Deprotonation of the racemic phosphonium salts [14-H]+ PF6–. a) t-BuOK (1.5 equiv.),

C6H6.

These phosphines were all characterized by elemental analysis, NMR (1H, 13C{1H},

31P{1H}) and IR spectroscopy, mass spectrometry, and melting points. Melting again occurred with

decomposition, as the trivalent phosphorus center is sensitive to oxygen and the analysis is

conducted under air.

Again, the 13C{1H} NMR spectra showed a signal pattern analogous to that of the

phosphonium salts [14-H]+ PF6–. More interesting were the 31P{1H} NMR spectra, which were

very simple as each compound showed only two doublets; one for the RePPh3 and one for the

CH2PR2 group. The chemical shifts are summarized in Table 3.1. The shifts for the PPh3 ligands

are more or less similar. No trend is obvious. The same situation is found for the phosphorus-

phosphorus coupling constants of the complexes 14a-f.

Analyzing the chemical shifts of the CH2PR2 groups, there is a downfield trend upon going

from 14a (8.1 ppm)38 to 14d (2.8 ppm). In this series the para substituents become progressively

more electron releasing and the resonances shift progressively downfield. This behavior agrees with

the observation of Mayr that phenyl-substituents can modulate the electron density at the

phosphorus center and hence, the nucleophilicity of triarylphosphines (see also section 2.3.2).67

However, such conclusions cannot be reliably drawn concerning complexes 14e,f, as the extended π

system could have a strong effect on the shielding of the phosphorus atoms.

ON PPh3Re

CH2PR2H

PF6

14b: R = p-Tol, 80%

14c: R = p-C6H4OCH3, 77%

14d: R = p-C6H4N(CH3)2, 85%

14e: R = 2-biphen, 91%

14f: R = α-naph, 64%

a)

ON PPh3Re

CH2PR2

[14-H]+ PF6− 14


Table 3.1. 31P{1H} NMR shifts and coupling constants for the rhenium-containing phosphines 14a-

f.

(η5-C5H5)Re(NO)(PPh3)(CH2PR2), R =

Ph

(14a)a p-Tol (14b)b

p-C6H4OCH3

(14c)b

p-C6H4N(CH3)2

(14d)b

2-biphen2

(14e)c

α-naph2

(14f)c

PPh3 25.8 27.2 27.6 27.2 23.9 25.7 δ (ppm) PR2 8.1 5.8 5.1 2.8 –5.7 –21.2

3J (Hz) (P,P) 8.0 6.7 6.9 6.7 6.9 6.9

a In CDCl3 (data from reference 38). b In C6D6. c In CD2Cl2.

The phosphines 14 were assumed to be sensitive to oxygen. Therefore, a sample of 14b was

kept under air in non-degassed C6D6. From time to time 1H and 31P{1H} NMR spectra were

recorded. These showed new signals, which were presumed to most likely be from oxidation

products, such as the phosphine oxide. In degassed solvents, these signals did not appear. The 1H

NMR spectra showed a new signal at 5.08 ppm (s), which was most likely from the

cyclopentadienyl ligand of the oxidized compound. The ratio of the cyclopentadienyl signal of the

oxidized phosphine compared to that of the unoxidized phosphine was utilized to assay the

operational availability of the catalyst during catalytic reactions. Other groups gave different 1H

NMR signals compared to the unoxidized phosphine, but these were not that diagnostic.

The 31P{1H} NMR spectra of the 14b exposed to oxygen showed two more doublets

appearing at 44.4 ppm (CH2(O=)P(p-Tol)) and 25.1 ppm (RePPh3). These chemical shift trends

parallel those reported for the 14a and O=14a analogs, which have been completely

characterized.61 Table 3.2 shows the ratio of 14b to the oxidation product as a function of time. It

takes 18 h to oxidize 16% of the phosphine. At the beginning, the oxidation is quite rapid, but then

slows down with time. Similar behavior was noted with the other rhenium-containing phosphines.


Table 3.2. Oxidation of 14b with time, assayed as described in the text.a

Time (h)

0.5 6 18

O=14b / 14b 4 / 96 7 / 93 16 / 84

a The amount of phosphine oxide was calculated by integration of the cyclopentadienyl

1H NMR signals.

3.2.1.2 Preparation of Enantiopure Complexes

As some of the complexes 14 showed good to excellent catalytic reactivity (Chapter 2), they

were synthesized in enantiopure form for enantioselective catalysis. These complexes are depicted

in Figure 3.1.

Figure 3.1. Enantiopure complexes (S)-14b-d, obtained from (S)-(η5-C5H5)Re(NO)(PPh3)(CH3)

((S)-26) by procedures analogous to the racemates (Schemes 3.2 and 3.3).

The procedures were carried out almost analogous to the racemic complexes. In general the

mechanism of product formation is the same in each case; however, solubilities can differ. Hence,

ON PPh3Re

CH2PR2H

PF6

(S)-[14b-H]+ PF6−: R = p-Tol, 86%

(S)-[14c-H]+ PF6−: R = p-C6H4OCH3, 95%

(S)-[14d-H]+ PF6−: R = p-C6H4N(CH3)2, 90%

ON PPh3Re

CH2PR2

(S)-14b: R = p-Tol, 88%

(S)-14c: R = p-C6H4OCH3, 87%

(S)-14d: R = p-C6H4N(CH3)2, 90%

(S)-[14-H]+ PF6− (S)-14


crystallization or precipitation from the product mixture was optimized by employing different

solvent mixtures, resulting in slightly changed workup procedures for the enantiopure complexes.

The complexes (S)-14b-d were characterized similarly to the racemic compounds. As expected, the

spectroscopic data were virtually identical. Since the salts (S)-[14(b-d)-H]+ PF6– were very air

stable they were also characterized by optical rotations. These showed that the complexes were at

least scalemic. In any case, the additions of carbon, nitrogen, phosphorus and sulfur nucleophiles to

the methylidene complex [(η5-C5H5)Re(NO)(PPh3)(=CH2)]+ PF6– have been shown to proceed

with essentially complete retention of configuration at the chiral center.75,86

3.2.1.3 Preparation of Diastereomeric Mixtures of P Chiral Complexes

As already mentioned in the Chapter 2, a new stereocenter was introduced at the phosphorus

atom of the rhenium-containing phosphines. This was done by applying the same procedures as

above, but with the racemic secondary phosphines PPh(α-naph)H (29c) and PPh(β-naph)H (29d)

(Scheme 3.4).

Scheme 3.4. Preparation of the protonated diastereomeric rhenium-containing phosphines

(SReRP)/(SReSP)-[17-H]+ PF6–. a) Ph3C+ PF6

–, CH2Cl2. b) PRR'H.

Again, the sequence started with enantiopure (S)-2682 reacting with Ph3C+ PF6–, followed

by the addition of 29c,d. Only two of four possible stereoisomers were expected to be formed, as

the rhenium configuration should be retained. Indeed, mixtures of (SReSP)-17c and (SReRP)-17c or

ON PPh3Re

CH3

ON PPh3Re

CH2PRR'H∗

PF6

(SReRP)/(SReSP)-[17c-H]+ PF6−: R/R' = Ph/α-naph, 78%

(SReRP)/(SReSP)-[17d-H]+ PF6−: R/R' = Ph/β-naph, 83%

a)

b)

(SReRP)/(SReSP)-[17-H]+ PF6−(S)-26


(SReSP)-17d and (SReRP)-17d were detected. Importantly, some reactions were carried out with a

large excess of the racemic phosphine 29c, in hopes that a matched diastereomer might

preferentially form. In these cases, the reaction solution was very slowly warmed from –78 °C to

room temperature overnight. However, 1H NMR spectra of an aliquot showed a diastereomeric

mixture (Figure 3.2). Since the sample did not completely dissolve in CD2Cl2, no integration values

are given.

Figure 3.2. Partial 1H NMR spectrum (CD2Cl2) of an aliquot of the reaction mixture that yields

(SReSP)/(SReRP)-[17c-H]+ PF6– (δ in ppm).

One of the cyclopentadienyl singlets in Figure 3.2 is arbitrarily assigned as diastereomer 1

and the other as diastereomer 2. The shift difference between the diastereomers is 0.34 ppm. This is

quite large and suggests significantly different steric and electronic environments.

Also the solubility and stability of the diastereomers differ. To precipitate a mixture

enriched in diastereomer 1, the volume of the reaction mixture was reduced to one third and n-

pentane was added slowly with vigorous stirring until a precipitate first appeared. Then the mixture

was cooled to –24 °C. After 24 h, the precipitate was isolated by filtration to give diastereomer 1 in

72% de, as assayed by the ratio of the integrals of the cyclopentadienyl 1H NMR signals (CD3CN,

homogenous conditions). After a second identical precipitation, diastereomer 1 was obtained in

92% de. This reaction was repeated several times and in some cases a third precipitation cycle was

necessary to obtain good de values.

5.5 5.06.0 4.5 4.0

CDHCl2

C5H5(Dia_1)

C5H5(Dia_2)

ppm


Noteworthy is the fact that diastereomer 1 never precipitated from the reaction mixture with

the solvent CH2Cl2 itself. Addition of n-pentane was always obligatory. But when highly

diastereoenriched powders of diastereomer 1 were treated with CH2Cl2 or CHCl3 they showed poor

solubilities. These mixtures were soluble in acetone but after several hours the solutions darkened,

indicative of decomposition. Good solubility was also found in CH3CN, so the NMR spectra were

recorded in this solvent. But also here decomposition was detected by 1H NMR as time went by.

Diastereomer 2 enriched mixtures showed a totally different behavior. These mixtures were

obtained from the supernatants from diastereomer 1 precipitations. To precipitate diastereomer 2, a

large excess of n-pentane was necessary. The best obtained de value for this mixture was –92%. In

Figure 3.3 the cyclopentadienyl 1H NMR signals of diastereoenriched mixtures are shown.

Figure 3.3. Partial 1H NMR spectra (CD3CN) of diastereomeric mixtures of (SReSP)/(SReRP)-[17c-

H]+ PF6– (δ in ppm), de = 92% and –92%.

Diastereomer 2 enriched mixtures showed very good solubilities in CH2Cl2 as well as in

CHCl3. Also in CH3CN and acetone very good solubilities were noticed, but decomposition

occurred within hours. The color darkens within tens of minutes. Because of this, the 13C{1H} and

31P{1H} NMR spectra of these mixtures were recorded in CD2Cl2. Hence, the chemical shifts are

not fully comparable with those for diastereomer 1 in the experimental section (where NMR data

was collected in CD3CN due to better solubility). NMR and other physical properties are

ppm

5.1 1.00 0.04 1.00 0.04

C5H5(Dia_1)

Diastereomer 1 enriched mixture Diastereomer 2 enriched mixture

C5H5(Dia_2)

5.0 4.9 4.8 5.1 5.0 4.9 4.8

C5H5(Dia_1)

C5H5(Dia_2)


summarized in Table 3.3.

Table 3.3. Comparison of selected physical properties of diastereomers 1 and 2 of (SReSP)/(SReRP)-

[17c-H]+ PF6–.

Diastereomer 1 Diastereomer 2

PPh3 21.2 22.3

PPh(α-naph)H 23.1 29.0 31P{1H} NMR

signala 3J(P,P) 14.1 12.6

C5H5 4.98 4.64 1H NMR signala CHH' m (2.82-2.54, 2H) 2 m (3.06-2.91, 1H; 2.82-2.54, 1H)

IRb νNO 1644 1652

CH3CN good (dec. within 24 h) very good (dec. within 30 min)

acetone good (dec. within 24 h) very good (dec. within several h)

CH2Cl2 low very good solubility

CHCl3 low (dec. within 24 h) very good (dec. within several h)

a δ in ppm, CD2Cl2. b cm–1, thin film.

Notably, the strong IR νNO bands differ by 8 cm–1. However, this is not useful as a de assay,

as only one broader band is observed if a diastereomeric mixture with low de is sampled. But this

nicely shows that the electronic structures of the diastereomeric complexes are modified by the

phosphorus stereocenter. The NO ligand is a good π-acceptor as there is a vacant π* orbital that can

take up electron density. The more electron density is found in the π* orbital, the lower the bond

order. The lower the bond order, the lower the energy needed to excite the vibration. This means

that the complex with the higher electron density has the lower IR wave number. In this case it is

diastereomer 1 (1644 cm–1). This is supported by the PPh3 31P{1H} NMR signal. Diastereomer 1 is

upfield of diastereomer 2, suggesting a higher electron density at the phosphorus atom in

diastereomer 1 (21.2 ppm vs. 22.3 ppm).


As each diastereomer of (SReSP)/(SReRP)-[17c-H]+ PF6– could be obtained with a de > 90%,

each was characterized by elemental analysis, NMR (1H, 13C{1H}, 31P{1H}) and IR spectroscopy,

and mass spectrometry. The complete assignment of 13C{1H} NMR signals was not possible, due

to many overlapping aryl resonances as well as some small signals from the opposite diastereomer.

Since the samples were not diastereomerically pure, optical rotations and melting points were not

measured.

Unfortunately, the diastereomers of (SReSP)/(SReRP)-[17d-H]+ PF6– could not be as

efficiently separated and only low de values were obtained (48% and –38%). Hence, the

diastereomer separation at this stage is not detailed in the experimental section. The solubility

properties of the diastereomers were too similar to get good separation. Furthermore, decomposition

was noticed in many solvents. Even treating the crude reaction mixture with n-pentane to precipitate

the product gave a black mixture and an impure oily precipitate. Only precipitation with diethyl

ether gave the desired product as a powder, although here the supernatant also showed a very dark

coloring, indicating decomposition. However, no diastereomeric enrichment took place. When this

solid was treated with ethyl acetate, one diastereomer preferentially dissolved. Nonetheless, all

attempts to separate the diastereomers of (SReSP)/(SReRP)-[17d-H]+ PF6– were unsuccessful. Thus,

the characterization was carried out with the diastereomeric mixture. Elemental analysis, NMR (1H,

13C{1H}, 31P{1H}) and IR spectroscopy, and mass spectrometry data are summarized in the

experimental section. Since the samples were not diastereomerically pure, optical rotations and

melting points were not measured.

The deprotonation of (SReSP)/(SReRP)-[17c-H]+ PF6– was carried out analogous to that in

Scheme 3.3. The diastereoenriched mixtures were treated with t-BuOK in C6H6. After filtration

through a plug of Celite®, the solvent volume was reduced and the solution was layered with n-

pentane. The phosphine (SReSP)/(SReRP)-17c precipitated and was characterized by NMR (1H and

31P{1H}). The de remained unchanged, as assayed by integration of the cyclopentadienyl 1H NMR

signals, consistent with retention of configuration at rhenium and phosphorus atoms. The resulting

solids were then employed as catalysts (section 2.4.1.2).

A 50:50 diastereomeric mixture of (SReSP)/(SReRP)-[17d-H]+ PF6– was similarly

deprotonated with t-BuOK in C6H6. After reduction of the C6H6 volume, a layer of n-pentane was


added. A dark red precipitate was collected by filtration. The 1H NMR spectrum proved that

(SReSP)/(SReRP)-17d was obtained, and integration of the cyclopentadienyl signals indicated a 48%

de. The enriched diastereomer was arbitrarily assigned to be diastereomer 1.

The filtrate was treated with more n-pentane and the opposite diastereomer 2 of

(SReSP)/(SReRP)-17d precipitated with –92% de. Both precipitates were characterized by 1H NMR

and 31P{1H} NMR spectroscopy and employed for catalysis.

Complexes (SReSP)/(SReRP)-[17a-H]+ PF6– and (SReSP)/(SReRP)-[17b-H]+ PF6

–, which

were obtained from Dante Castillo,52 were deprotonated in the same manner as above, and the

resulting orange solids were employed for organocatalytic reactions without further characterization

or purification.

3.2.1.4 Preparation of (SReSC)-[(η5-C5H5)Re(NO)(PPh3)(CHCH3PPh2H)]+ PF6– ((SReSC)-

[15b-H]+ PF6–)

The preparation of (SReSC)-[15b-H]+ PF6–, which features both rhenium and carbon

stereocenters, was carried out analogous to the previously reported phenyl analog (SReSC)-[15a-H]+

PF6– (Scheme 3.1).51 The sequence started with the rhenium ethyl complex (S)-(η5-C5H5)Re(NO)-

(PPh3)(CH2CH3),89 which was treated as shown in Scheme 3.5.

When the rhenium ethyl complex and Ph3C+ PF6– were combined in CH2Cl2 at –78 °C, an

α hydride was regiospecifically abstracted to give the ethylidene complex (sc)-[(η5-

C5H5)Re(NO)(PPh3)(=CH2CH3)]+ PF6–. This species was not isolated, but has been extensively

studied earlier.89 It is very important to keep the temperature at –78 °C. If the mixture is warmed,

the opposite (ac) Re=C isomer of the ethylidene complex is formed and the opposite

stereospecificity is obtained. Therefore, PPh2H was added at low temperature. This reacted with the

ethylidene complex upon warming to give the phosphonium salt (SReSC)-[15b-H]+ PF6–. The crude

product was precipitated from the reaction mixture by the addition of n-pentane, and isolated by

decantation as an oil that solidified with drying by oil pump vacuum.

The solid was precipitated a second time from a CH2Cl2/t-BuOH solution by slowly

concentrating the sample under vacuum with vigorous stirring. The product (SReSC)-[15b-H]+ PF6–


precipitated, and was characterized by elemental analysis, NMR (1H, 13C{1H}, 31P{1H}) and IR

spectroscopy, mass spectrometry, and melting point. No evidence for a second diastereomer was

observed. The carbon configuration was assigned by analogy to other addition products of

ethylidene and benzylidene complexes that have been crystallographically characterized.40

Scheme 3.5. Preparation of the diastereopure rhenium-containing phosphine (SReSC)-[15b-H]+

PF6–. a) Ph3C+ PF6

–, CH2Cl2, –78 °C. b) PPh2H.

The (SReSC)-[15b-H]+ PF6– was subsequently treated with t-BuOK (1.5 equiv.) in C6H6.

After the deprotonation was finished, the mixture was filtered through a plug of Celite®. Then the

solvent volume was reduced and n-pentane was added. The deprotonated complex 15b precipitated,

and was employed without purification or characterization for catalysis (section 2.2.1.5).

3.2.2 Preparation of Secondary Phosphines

For the syntheses of the above rhenium-containing phosphines, secondary phosphines of the

formula PRR'H were needed. In the case of R = R' = Ph, or p-Tol, both compounds were

commercially available. All others had to be synthesized. Two different synthetic routes were

evaluated. One involved the reduction of a phosphine oxide and the other was the reduction of a

ON PPh3Re

CH2CH3

ON PPh3Re

C

PF6

a) b)

(SReSC)-[15b-H]+ PF6−, 55%

H

CH3HPh2P(S)

ON PPh3H

CH3

ON PPh3Re

C

H CH3

PF6


diarylchlorophosphine.

3.2.2.1 Preparation via Reduction of Secondary Phosphine Oxides

The preparation of secondary phosphines oxides, as well as their reduction to secondary

phosphines, is a well known procedure reported by Busacca.87 The usual sequence is shown in

Scheme 3.6.

Scheme 3.6. Syntheses of the secondary phosphines 28c,d (yields overall). a) Mg, THF. b)

OP(OEt)2H. c) DIBAL-H. d) NaOH/H2O.

The literature procedure was followed exactly and the therein reported secondary phosphine

oxides were purified by crystallization. The second step, the reduction with DIBAL-H was nearly

quantitative. The phosphines 28c,d were obtained with satisfactory purity and no further

manipulations after hydrolysis were necessary.

3.2.2.2 Preparation via Reduction of Diarylchlorophosphines

The above method for the preparation of phosphines is a very useful one. However, when

extended to the naphthyl and biphenyl analogs, the secondary phosphine oxides proved to be poorly

soluble in nonprotic solvents. Protic solvents on the other hand did not precipitate products for

purification. Hence, another procedure was applied.

OPR2H PR2H

28c: R = p-C6H4OCH3, 73%

28d: R = p-C6H4N(CH3)2, 67%

a)

b) 28

RBrc)

d)


Preparation of symmetric secondary phosphines. Two phosphines PR2H (R = 2-biphen

(28e), α-naph (28f)) were synthesized by the reaction of Grignard reagents with phosphorus

trichloride, followed by the reduction with LiAlH4. They were obtained via a three step synthesis

without isolation of the intermediates (Scheme 3.7).

Scheme 3.7. Synthesis of the secondary phosphines 28e,f. a) Mg, THF. b) PCl3. c) LiAlH4. d)

NaOH/H2O.

Grignard reagents were prepared from the commercially available aryl bromides RBr (R =

2-biphen, α-naph). Then the reagents (2.2 equiv.) were added dropwise to dilute solutions of

phosphorus trichloride at 0 °C. After warming to room temperature, 31P{1H} NMR spectra of

aliquots indicated full conversion of phosphorus trichloride as the signal (231 ppm) disappeared.

The 31P{1H} NMR spectra exhibited several peaks. In addition to some small unassigned signals,

the crude products exhibited two signals that differed by 5-10 ppm. These were provisionally

assigned as the target PR2Cl species and the corresponding PR2Br compound, with the bromide

derived from the Grignard reagents. For P(α-naph)2X, signals were observed at 77.7 ppm and 68.9

ppm (ca. 1:1, X = Cl and Br, respectively). For P(2-biphen)2X a dominant signal at 75.4 ppm and

another small signal at 69.8 ppm were found (ca. 10:1, X = Cl and Br, respectively). No signals

characteristic of tertiary phosphines were noted in the samples of 28e. In contrast, samples of 28f

exhibited several small signals at ca. –45 ppm, which could indicate the presence of the tertiary

phosphine P(α-naph)3.

These mixtures were treated with excesses of LiAlH4, and after a few minutes 31P{1H}

NMR spectra indicated total consumption of the PR2Cl species. In both cases one major signal for

the secondary phosphine was obtained (28e: –53.1 ppm, 28f: –61.9 ppm). The 31P{1H} NMR

spectrum of crude 28e showed one more signal at –124.7 ppm, suggesting the presence of some

primary phosphine P(2-biphen)H2. Crude 28f also showed one more but very small signal at –135.1

RBr

a)b)c)d)

PR2H28e: R = 2-biphen, 70%

28f: R = α-naph, 35%28


ppm, which was also supposed to be the corresponding primary phosphine.

The secondary phosphine 28f could be purified by Kugelrohr distillation with subsequent

crystallization, while for 28e crystallization alone was sufficient. This gave the pure phosphines in

moderate and good yields (28e: 70%, 28f: 35%). Since 28e was a new compound, it was

characterized by NMR spectroscopy (1H, 13C{1H}, 31P{1H}). The secondary phosphine 28f had

been mentioned in the literature.88 The reported procedure was different but not reproducible in the

author's hands. However, 1H NMR and 31P{1H} NMR data for 28f matched that previously

reported.

Preparation of racemic secondary phosphines. The racemic secondary phosphines PRR'H

(R/R' = Ph/α-naph (29c); Ph/β-naph (29d)) required for the rhenium-containing phosphines

(SReSP)/(SReRP)-17c and (SReSP)/(SReRP)-17d were obtained by a procedure similar to the

symmetric ones. This route is depicted in Scheme 3.8.

Scheme 3.8. Synthesis of the racemic secondary phosphines 29c,d. a) Mg, THF. b) PPhCl2. c)

LiAlH4. d) NaOH/H2O.

The Grignard reagents (1.1 equiv.) were added to commercially available PPhCl2. Also here

mixtures of the PRR'X species (X = Cl, Br) were obtained. These were treated with LiAlH4, and

subsequently with aqueous NaOH. In this case both pure phosphines were obtained by Kugelrohr

distillation in moderate yields (29c: 38%, 29d: 32%). Both phosphines were characterized by NMR

spectroscopy (1H, 13C{1H}, 31P{1H}).

3.3 Discussion

This chapter has established that many phosphines [Re]CH2PRR' with the rhenium fragment

RBr

a)b)c)d)

PRR'H29c: R/R' = Ph/α-naph, 38%

29d: R/R' = Ph/β-naph, 32%29


[Re] = (η5-C5H5)Re(NO)(PPh3) can be easily synthesized in good to excellent yields. Furthermore

many of these are readily obtained in enantiopure form.

However, with increasing numbers of reaction steps, it is more important to obtain good

yields for each step. For example, the overall yield for the known complex 14a is 44% for the

racemate (6 steps); if the enantiopure form is needed the yield decreases to 36% (9 steps). The new

catalysts 14b-f and (SReSP)/(SReRP)-17c,d have been synthesized in comparable yields. However,

excluding 14b which is prepared using commercially available P(p-Tol)2H, those catalysts require

secondary phosphines that must themselves be synthesized. As these preparations are also multistep

procedures giving low to good yields (32-70%), the economics of the catalyst preparation becomes

less attractive. However, the routes employed are very flexible with respect to the phosphorus

substituents, and as noted in the previous chapter these exert a tremendous influence upon the

enantioselectivities. In the event that a commercial catalyst of this type were developed, it is

probable that via careful optimization an economical, high-yield synthetic sequence could be

developed.


3.4 Experimental

3.4.1 General Data

All experiments were conducted under N2, except in the cases where simple distilled

solvents were employed. NMR spectra were recorded at ambient probe temperature on Bruker 300

and 400 MHz FT spectrometers and referenced to the residual solvent signal (1H: CHCl3, 7.26 ppm;

CHDCl2, 5.32 ppm; C6D5H, 7.27 ppm; 13C{1H}: CDCl3, 77.0 ppm; CD2Cl2, 53.8 ppm; C6D6,

128.0 ppm) or H3PO4 (31P{1H}, external capillary, 85%, 0.0 ppm). IR spectra were recorded on an

ASI React IR®-1000 spectrometer. Optical rotations were measured using a Perkin-Elmer model

341 polarimeter. Mass spectra were obtained using a Micromass Zabspec instrument. Elemental

analyses were determined with a Carlo Erba EA1110 CHN instrument. Melting points were

measured on an Electrothermal IA 9100 apparatus.

Solvents were treated as follows: THF, n-pentane (2 × Grüssing), distilled from sodium

/benzophenone; CH2Cl2 (Staub) and C6H6 (Grüssing), distilled from CaH2; t-BuOH (Grüssing),

distilled from Mg; diethyl ether (Hedinger), hexanes, CH3OH, and EtOH (3 × Staub), simple

distilled; CDCl3 (99.8%), CD2Cl2 (99.6%), CD3CN (99.0%), and C6D6 (99.5%, 4 × Deutero

GmbH), freeze-pump-thaw degassed (3 ×) in the case of air sensitive products.

Chemicals were treated as follows: Ph3C+ PF6– (≥ 95%, Fluka),90 stored under argon at –30

°C; PCl3 (Merck) and PPhCl2 (97%, Acros), distilled and stored under N2; LiAlH4 (95%), t-BuOK

(98+%), 2-biphenylbromide (3 × Acros), α-naphthylbromide (96%, Fluka), β-naphthylbromide

(97% Lancaster), and P(p-Tol)2H (28b, 99%, Strem), used as received.

Silica gel 60M (Macherey-Nagel) and Celite® 535 (Fluka) for filtration, used as received.


3.4.2 Preparation of Rhenium-Containing Phosphines

[(η5-C5H5)Re(NO)(PPh3)(CH2P(p-Tol)2H)]+ PF6– ([14b-H]+ PF6

–). A Schlenk flask was

charged with racemic (η5-C5H5)Re(NO)(PPh3)(CH3) (26, 0.244 g, 0.437 mmol)82 and CH2Cl2 (15

mL). The solution was cooled to –78 °C and Ph3C+ PF6– (0.187 g, 0.481 mmol) was added with

stirring. After 1 h, P(p-Tol)2H (28b, 0.112 g, 0.787 mmol) dissolved in CH2Cl2 (1 mL) was added.

After 20 min, the cold bath was removed. After 1 h, the mixture was concentrated by oil pump

vacuum (to ca. 2.5 mL) and added dropwise to stirred hexanes (25 mL). An orange powder

precipitated, which was collected by filtration and washed with n-pentane (3 × 5 mL). A

31P{1H}NMR spectrum still showed some 28b. The powder was dissolved in CH2Cl2 (3 mL) and

C6H6 (15 mL). Hexanes (15 mL) were added with stirring and again an orange powder precipitated,

which was collected by filtration, washed with hexanes (2 × 5 mL) and n-pentane (5 × 5 mL), and

dried by oil pump vacuum to give pure [14b-H]+ PF6– (0.376 g, 0.411 mmol, 94%). M.p. 179-181

°C, dec. (capillary). Elemental analysis calcd (%) for C38H37F6NOP3Re (917.2): C 49.78, H 4.07,

N 1.53; found: C 49.45, H 3.98, N 1.50.

1H NMR (400 MHz, CD2Cl2, δ in ppm): 7.73-7.65, 7.51-7.43, 7.37-7.30 (3 m, C6H5 and

C6H4, 23H), 6.91 (dd, 1J(H,P) = 484 Hz, 3J(H,H) = 13.3 Hz, PH, 1H), 4.87 (s, C5H5, 5H), 2.65-

2.54 (m, CHH', 1H), 2.50, 2.40 (2 s, CH3 and CH3', 2 × 3H), 2.32-2.18 (m, CHH', 1H); 13C{1H}

NMR (101 MHz, CD2Cl2, δ in ppm): 91.0 (s, C5H5), –34.9 (dd, 1J(C,P) = 29.8 Hz, 2J(C,P) = 4.1

Hz, CHH'); PPh3 at91 134.4 (d, 1J(C,P) = 54.0 Hz, i), 134.0 (d, 2J(C,P) = 10.6 Hz, o), 131.6 (d,

4J(C,P) = 2.1 Hz, p), 129.5 (d, 3J(C,P) = 10.4 Hz, m); P(p-Tol)(p-Tol)' at 146.1 (d, 4J(C,P) = 2.8 Hz,

p to P), 145.5 (d, 4J(C,P) = 2.8 Hz, p' to P), 132.6 (d, 2J(C,P) = 10.6 Hz, o to P), 131.9 (d, 2J(C,P) =

10.5 Hz, o' to P), 131.2 (d, 3J(C,P) = 12.9 Hz, m to P), 130.9 (d, 3J(C,P) = 12.2 Hz, m' to P), 121.5

(d, 1J(C,P) = 71.8 Hz, i to P), 119.2 (d, 1J(C,P) = 88.2 Hz, i' to P), 22.1, 22.0 (2 s, CH3 and CH3');

31P{1H} NMR (162 MHz, CD2Cl2, δ in ppm): 28.8 (d, 3J(P,P) = 10.9 Hz, PH), 21.7 (d, 3J(P,P) =

10.9 Hz, PPh3), –144.0 (sept, 1J(P,F) = 708 Hz, PF6).

IR (thin film, cm–1):71 1668 (s, νNO). MS:92 772 (90) [14b-H]+, 558 (100) [14b–P(p-

Tol)2H]+.


(S)-[(η5-C5H5)Re(NO)(PPh3)(CH2P(p-Tol)2H)]+ PF6– ((S)-[14b-H]+ PF6

–). A Schlenk

flask was charged with (S)-26 (0.250 g, 0.448 mmol)82 and CH2Cl2 (15 mL). The solution was

cooled to –78 °C and Ph3C+ PF6– (0.191 g, 0.493 mmol) was added with stirring. After 1 h, 28b

(0.115 g, 0.787 mmol) dissolved in CH2Cl2 (1 mL) was added. After 20 min, the cold bath was

removed. After 1 h, the mixture was concentrated by oil pump vacuum (to ca. 2.5 mL) and EtOH (7

mL) was added with stirring. A yellow powder precipitated, and the solvent volume was reduced by

oil pump vacuum (to ca. 6 mL). The mixture was kept at –20 °C. After 2 h, the yellow powder was

collected by filtration, washed with EtOH (1 mL) and hexanes (2 × 5 mL), and dried by oil pump

vacuum to give pure (S)-[14b-H]+ PF6– (0.353 g, 0.385 mmol, 86%). M.p. 179-180 °C, dec.

(capillary). Elemental analysis calcd (%) for C38H37F6NOP3Re (917.2): C 49.78, H 4.07, N 1.53;

found: C 49.50, H 4.12, N 1.54. [α]26589 = 257° ± 1° (c = 2.00 mg/mL, CH2Cl2). Spectroscopic

data were similar to those of the racemate.

(η5-C5H5)Re(NO)(PPh3)(CH2P(p-Tol)2) (14b). A Schlenk flask was charged with [14b-

H]+ PF6– (0.161 g, 0.191 mmol) and C6H6 (20 mL). The suspension was vigorously stirred and t-

BuOK (0.0321 g, 0.287 mmol) was added. After 1 h, the orange suspension was filtered through a

plug of Celite®. The plug was rinsed with C6H6 until the filtrate became colorless. The filtrate was

concentrated by oil pump vacuum (to ca. 2 mL), layered with n-pentane (15 mL), and kept at 4 °C.

After 48 h, the orange crystals were collected by filtration and dried by oil pump vacuum to give

14b (0.118 g, 0.153 mmol, 80%). Dec. pt. 160-162 °C (capillary). Elemental analysis calcd (%) for

C38H36NOP2Re (770.9): C 59.21 H 4.71, N 1.82; found: C 58.98, H 4.98, N 1.81.

1H NMR (300 MHz, C6D6, δ in ppm): 7.74 (apparent t, 3J(H,H) = 3J(H,P) = 7.0 Hz, C6H4,

o to P, 2H), 7.66 (apparent t, 3J(H,H) = 3J(H,P) = 7.0 Hz, C6H4', o to P, 2H), 7.53 (dd, 3J(H,P) =

11.6 Hz, 3J(H,H) = 9.6, o-C6H5, 6H), 7.12-6.93 (m, m-, p-C6H5 and C6H4, m to P, 13H), 4.55 (s,

C5H5, 5H), 2.83 (dd, 2J(H,H) = 11.6 Hz, J(H,P) = 9.7 Hz, CHH', 1H), 2.12, 2.08 (2 s, CH3 and

CH3', 2 × 3H), 2.15-2.05 (m, CHH', 1H); 13C{1H} NMR (76 MHz, C6D6, δ in ppm): 89.9 (s, C5H5),

–18.1 (dd, 1J(C,P) = 37.2 Hz, 2J(C,P) = 4.7 Hz CHH'); PPh3 at 136.6 (d, 1J(C,P) = 50.8 Hz, i),


134.0 (d, 2J(C,P) = 10.2 Hz, o), 130.1 (s, p), 128.5 (d, 3J(C,P) = 10.2 Hz, m); P(p-Tol)(p-Tol)' at

144.7 (d, 1J(C,P) = 20.6 Hz, i to P), 143.4 (d, 1J(C,P) = 19.8 Hz, i' to P), 137.0, 136.6 (2 s, p and p'

to P), 133.7 (d, 2J(C,P) = 18.6 Hz, o to P), 133.1 (d, 2J(C,P) = 17.6 Hz, o' to P), 128.9 (d, 3J(C,P) =

4.9 Hz, m to P), 128.9 (d, 3J(C,P) = 5.8 Hz, m' to P), 21.3, 21.2 (2 s, CH3 and CH3'); 31P{1H} NMR

(121 MHz, C6D6, δ in ppm): 26.8 (d, 3J(P,P) = 6.7 Hz, PPh3), 5.8 (d, 3J(P,P) = 6.7 Hz, P(p-Tol)2)).

IR (thin film, cm–1):71 1644 (s, νNO). MS:92 771 (11) [14b]+, 558 (100) [14b–P(p-Tol)2]+.

(S)-(η5-C5H5)Re(NO)(PPh3)(CH2P(p-Tol)2) ((S)-14b). (S)-[14b-H]+ PF6– (0.187 g, 0.204

mmol), t-BuOK (0.0343 g, 0.306 mmol), and C6H6 (20 mL) were combined in a procedure

analogous to that given for the racemate. An identical workup gave (S)-14b as an orange powder

(0.138 g, 0.180 mmol, 88%). Dec. pt. 125-130 °C (capillary). Spectroscopic data were similar to

those of the racemate.

[(η5-C5H5)Re(NO)(PPh3)(CH2P(p-C6H4OCH3)2H)]+ PF6– ([14c-H]+ PF6

–). A Schlenk

flask was charged with racemic 26 (0.246 g, 0.441 mmol)82 and CH2Cl2 (15 mL). The solution was

cooled to –78 °C and Ph3C+ PF6– (0.188 g, 0.485 mmol) was added with stirring. After 1 h, P(p-

C6H4OCH3)2H (28c, 0.141 g, 0.573 mmol)87 dissolved in CH2Cl2 (1 mL) was added dropwise.

After 20 min, the cold bath was removed. After 1 h, the sample was concentrated by oil pump

vacuum (to ca. 4 mL). A CH3OH/EtOH mixture (2.5 mL, 2:3 v/v) was added, followed by CH2Cl2

until the sample became homogeneous. Hexanes (ca. 20 mL) were added with stirring and an

orange powder precipitated, which was collected by filtration, washed with hexanes (3 × 3 mL), and

dried by oil pump vacuum to give pure [14c-H]+ PF6– (0.369 g, 0.389 mmol, 88%). M.p. 207-208

°C, dec. (capillary). Elemental analysis calcd (%) for C38H37F6NO3P3Re (949.1): C 48.10, H 3.93,

N 1.48; found: C 47.76, H 3.84, N 1.45.

1H NMR (400 MHz, CDCl3, δ in ppm): 7.78 (dd, 3J(H,P) = 13.0, 3J(H,H) = 8.5 Hz, C6H4, o

to P, 2H), 7.31-7.49 (m, C6H5 and C6H4', o to P, 17H), 7.12 (d, 3J(H,H) = 8.8 Hz, C6H4, m to P,

2H), 6.96 (d, 3J(H,H) = 8.5 Hz, C6H4', m to P, 2H), 6.90 (dd, 1J(H,P) = 478 Hz, 3J(H,H) = 12.0 Hz,

PH, 1H), 4.90 (s, C5H5, 5H), 3.89, 3.83 (2 s, OCH3 and OCH3', 2 × 3H), 2.68 (apparent dt, 2J(H,H)

= 19.8 Hz, J(H,P) = 3J(H,H) = 14.5 Hz, CHH', 1H), 2.50 (dd, 2J(H,H) = 19.8 Hz, J(H,P) = 12.2 Hz


CHH', 1H); 13C{1H} NMR (101 MHz, CD2Cl2, δ in ppm): 90.9 (s, C5H5), –34.0 (dd, 1J(C,P) =

30.8 Hz, 2J(C,P) = 4.4 Hz, CHH'); PPh3 at 134.4 (d, 1J(C,P) = 40.0 Hz, i), 134.0 (d, 2J(C,P) = 10.4

Hz, o), 131.6 (d, 4J(C,P) = 2.4 Hz, p), 129.5 (d, 3J(C,P) = 10.4 Hz, m); P(C6H4OCH3)(C6H4OCH3)'

at 164.8 (d, 4J(C,P) = 2.8 Hz, p to P), 164.4 (d, 4J(C,P) = 2.4 Hz, p' to P), 134.71, 134.70 (2 s, m

and m' to P), 116.2 (d, 2J(C,P) = 13.6 Hz, o to P), 115.8 (d, 2J(C,P) = 12.8 Hz, o' to P), 115.5 (d,

1J(C,P) = 75.9 Hz, i to P), 113.0 (d, 1J(C,P) = 92.7 Hz, i' to P), 56.3, 55.2 (2 s, OCH3 and OCH3');

31P{1H} NMR (162 MHz, CDCl3, δ in ppm): 29.2 (d, 3J(P,P) = 10.9 Hz, PH), 23.1 (d, 3J(P,P) =

10.9 Hz, PPh3), –142.9 (sept, 1J(P,F) = 708 Hz, PF6).

IR (thin film, cm–1):71 1640 (s, νNO). MS:92 804 (100) [14b-H]+, 558 (90) [14b–P(p-

C6H4OCH3)2H]+.

(S)-[(η5-C5H5)Re(NO)(PPh3)(CH2P(p-C6H4OCH3)2H)]+ PF6– ((S)-[14c-H]+ PF6

–).

Complex (S)-26 (0.399 g, 0.715 mmol),82 CH2Cl2 (20 mL), Ph3C+ PF6– (0.305 g, 0.787 mmol),

28c (0.211 g, 0.858 mmol),87 and CH2Cl2 (1 mL) were combined in a procedure analogous to that

given for the racemate. An identical workup gave (S)-[14c-H]+ PF6– as an orange powder (0.645 g,

0.680 mmol, 95%). M.p. 204-205 °C, dec. (capillary). Elemental analysis calcd (%) for

C38H37F6NO3P3Re (949.1): C 48.10, H 3.93, N 1.48; found: C 47.98, H 3.67, N 1.45. [α]25589 =

248° ± 1° (c = 2.00 mg/mL, CH2Cl2). Spectroscopic data were similar to those of the racemate.

(η5-C5H5)Re(NO)(PPh3)(CH2P(p-C6H4OCH3)2) (14c). A Schlenk flask was charged

with [14c-H]+ PF6– (0.154 g, 0.162 mmol) and C6H6 (10 mL). The suspension was vigorously

stirred and t-BuOK (0.0273 g, 0.243 mmol) was added. After 1 h, the orange suspension was

filtered through a plug of Celite®. The plug was rinsed with C6H6 until the filtrate became colorless.

The filtrate was concentrated by oil pump vacuum (to ca. 2 mL), layered with n-pentane (15 mL),

and kept at 4 °C. After 48 h, the orange crystals were collected by filtration and dried by oil pump

vacuum to give 14c (0.100 g, 0.125 mmol, 77%). Dec. pt. 162 °C (capillary). Elemental analysis

calcd (%) for C38H36NO3P2Re (802.9): C 56.85, H 4.52, N 1.74; found: C 56.38, H 4.46, N 1.74.

1H NMR (400 MHz, C6D6, δ in ppm): 7.74 (dd, 3J(H,H) = 8.6 Hz, 3J(H,P) = 5.8 Hz, C6H4,

o to P, 2H), 7.68 (dd, 3J(H,H) = 8.6, 3J(H,P) = 5.8 Hz, C6H4', o to P, 2H), 7.56-7.50 (m, o-C6H5,


6H), 7.07-7.01, 7.00-6.95 (2 m, m-, p-C6H5, 9H), 6.91 (d, 3J(H,H) = 8.6 Hz, C6H4, m to P, 2H),

6.79 (d, 3J(H,H) = 8.6 Hz, C6H4', m to P, 2H), 4.59 (s, C5H5, 5H), 3.30, 3.27 (2 s, OCH3 and

OCH3', 2 × 3H), 2.83 (dd, 2J(H,H) = 11.9 Hz, J(H,P) = 9.7 Hz, CHH', 1H), 2.09 (dd, 2J(H,H) =

11.9 Hz, J(H,P) = 2.5 Hz, CHH', 1H); 13C{1H} NMR (101 MHz, CD2Cl2, δ in ppm): 90.3 (s,

C5H5), –18.1 (dd, 1J(C,P) = 35.4 Hz, 2J(C,P) = 5.2 Hz, CHH'); PPh3 at 136.3 (d, 1J(C,P) = 51.6 Hz,

i), 134.1 (d, 2J(C,P) = 10.7 Hz, o), 130.5 (s, p), 128.8 (d, 3J(C,P) = 10.4 Hz, m);

P(C6H4OCH3)(C6H4OCH3)' at 159.8, 159.5 (2 s, p and p' to P), 138.4 (d, 1J(C,P) = 18.8 Hz, i to P),

137.4 (d, 1J(C,P) = 18.1 Hz, i' to P), 134.2 (d, 2J(C,P) = 20.6 Hz, o to P), 134.0 (d, 2J(C,P) = 18.4

Hz, o' to P), 113.7 (d, 3J(C,P) = 7.0 Hz, m to P), 113.6 (d, 3J(C,P) = 5.9 Hz, m' to P), 55.5, 55.4 (2 s,

OCH3 and OCH3'); 31P{1H} NMR (162 MHz, C6D6, δ in ppm): 27.6 (d, 3J(P,P) = 6.9 Hz, PPh3),

5.1 (d, 3J(P,P) = 6.9 Hz, P(C6H4OCH3)2).

IR (thin film, cm–1):71 1633 (s, νNO). MS:92 803 (10) [14c]+, 558 (100) [14c–P(p-

C6H4OCH3)2H]+.

(S)-(η5-C5H5)Re(NO)(PPh3)(CH2P(p-C6H4OCH3)2) ((S)-14c). (S)-[14c-H]+ PF6– (0.225

g, 0.237 mmol), t-BuOK (0.0398 g, 0.356 mmol), and C6H6 (20 mL) were combined in a procedure

analogous to that given for the racemate. An identical workup gave (S)-14c as an orange-red

powder (0.166 g, 0.206 mmol, 87%). M.p. 125-130 °C, dec. (capillary). Spectroscopic data were

similar to those of the racemate.

[(η5-C5H5)Re(NO)(PPh3)(CH2P(p-C6H4N(CH3)2)2H)]+ PF6– ([14d-H]+ PF6

–). A

Schlenk flask was charged with racemic 26 (0.212 g, 0.380 mmol)82 and CH2Cl2 (15 mL). The

solution was cooled to –78 °C and Ph3C+ PF6– (0.162 g, 0.418 mmol) was added with stirring.

After 1 h, P(p-C6H4N(CH3))2H (28d, 0.134 g, 0.494 mmol)87 dissolved in CH2Cl2 (1 mL) was

added dropwise. After 20 min, the cold bath was removed. After 1 h, the sample was concentrated

by oil pump vacuum (to ca. 4 mL). A CH3OH/EtOH mixture (5.5 mL, 4:5 v/v) was added, followed

by CH2Cl2 until the sample became homogeneous. Then hexanes (ca. 20 mL) were added with

stirring. The precipitate was washed with EtOH (2 × 1 mL) and hexanes (2 × 3 mL). After drying

by oil pump vacuum [14d-H]+ PF6– was obtained as an orange powder (0.345 g, 0.349 mmol, 93%).


M.p. 230-232 °C, dec. (capillary). Elemental analysis calcd (%) for C41H45F6N3OP3Re (989.2): C

49.28, H 4.45, N 4.31; found: C 48.91, H 4.39, N 4.22.

1H NMR (400 MHz, CDCl3, δ in ppm): 7.61 (dd, 3J(H,P) = 12.6 Hz, 3J(H,H) = 8.5 Hz,

C6H4, o to P, 2H), 7.49-7.42, 7.38-7.31 (2 m, C6H5, 15H), 7.26 (dd, 1J(H,P) = 472 Hz, 3J(H,H) =

10.7 Hz, PH, 1H), 7.18 (dd, 3J(H,P) = 12.1, 3J(H,H) = 8.6 Hz, C6H4', o to P, 2H), 6.80 (d, 3J(H,H)

= 8.6 Hz, C6H4, m to P, 2H), 6.62 (d, 3J(H,H) = 8.6 Hz, C6H4', m to P, 2H), 4.87 (s, C5H5, 5H),

3.07, 2.99 (2 s, CH3 and CH3', 2 × 6H), 2.52-2.37 (m, CHH', 2H); 13C{1H} NMR (101 MHz,

CD2Cl2, δ in ppm): 90.8 (s, C5H5), –32.0 (dd, 1J(C,P) = 33.3 Hz, 2J(C,P) = 3.4 Hz, CHH'); PPh3 at

134.7 (d, 1J(C,P) = 53.7 Hz, i), 134.0 (d, 2J(C,P) = 10.5 Hz, o), 131.5 (d, 4J(C,P) = 2.0 Hz, p),

129.5 (d, 3J(C,P) = 10.4 Hz, m); P(C6H4N(CH3)2)(C6H4N(CH3)2)' at 154.2 (d, 4J(C,P) = 1.9 Hz, p

to P), 153.7 (d, 4J(C,P) = 2.0 Hz, p' to P), 134.0 (d, 3J(C,P) = 11.5 Hz, m to P), 133.3 (d, 3J(C,P) =

11.5 Hz, m' to P), 112.6 (d, 2J(C,P) = 13.3 Hz, o to P), 112.3 (d, 2J(C,P) = 12.5 Hz, o' to P), 108.2

(d, 1J(C,P) = 79.9 Hz, i to P), 104.7 (d, 1J(C,P) = 98.9 Hz, i' to P), 40.3, 40.2 (2 s, CH3 and CH3');

31P{1H} NMR (162 MHz, CD2Cl2, δ in ppm): 28.7 (d, 3J(P,P) = 11.9 Hz, PH) 23.9 (d, 3J(P,P) =

11.9 Hz, PPh3), –142.9 (sept, 1J(P,F) = 714.4 Hz, PF6).

IR (thin film, cm–1):71 1645 (s, νNO). MS:92 830 (100) [14d-H]+, 558 (62) [14d–P(p-

C6H4N(CH3)2)2H]+.

(S)-[(η5-C5H5)Re(NO)(PPh3)(CH2P(p-C6H4N(CH3)2H)]+ PF6– ((S)-[14d-H]+ PF6

–).

Complex (S)-26 (0.300 g, 0.538 mmol),82 CH2Cl2 (15 mL), Ph3C+ PF6– (0.234 g, 0.603 mmol),

28d (0.175 g, 0.646 mmol),87 and CH2Cl2 (1 mL) were combined in a procedure analogous to that

given for the racemate. After the reaction mixture was stirred at room temperature for 1 h, the

sample was concentrated by oil pump vacuum (to ca. 3 mL). Then EtOH (7 mL) was added, and the

mixture was kept at –20 °C. After 2 h, the precipitate was collected by filtration, washed with EtOH

(1 mL) and hexanes (2 × 3 mL), and dried by oil pump vacuum to give (S)-[14d-H]+ PF6– as a

yellow powder (0.400 g, 0.410 mmol, 76%). M.p. 180-182 °C, dec. (capillary). Elemental analysis

calcd (%) for C40H43F6N3OP3Re (975.2): C 49.28, H 4.45, N 4.31; found: C 48.79, H 4.71, N 4.21.

[α]25589 = 202° ± 1° (c = 2.00 mg/mL, CH2Cl2). Spectroscopic data were similar to those of the

racemate.


(η5-C5H5)Re(NO)(PPh3)(CH2P(p-C6H4N(CH3)2) (14d). A Schlenk flask was charged

with [14d-H]+ PF6– (0.212 g, 0.217 mmol) and C6H6 (20 mL). The suspension was vigorously

stirred and t-BuOK (0.0365 g, 0.326 mmol) was added. After 1 h, the orange suspension was


The filtrate was concentrated by oil pump vacuum (to ca. 4 mL), layered with n-pentane (15 mL),

and kept at 4 °C. After 48 h, the orange crystals were collected by filtration and dried by oil pump

vacuum to give 14d as a red solid (0.153 g, 0.185 mmol, 85%). Dec. pt. 157-158 °C (capillary).

Elemental analysis calcd (%) for C41H44N3OP2Re (829.2): C 57.96, H 5.11, N 5.07; found: C

58.07, H 4.89, N 4.97.

1H NMR (300 MHz, C6D6, δ in ppm): 7.82 (dd, 3J(H,H) = 8.6 Hz, 3J(H,P) = 6.3 Hz, C6H4,

o to P, 2H), 7.76 (dd, 3J(H,H) = 8.6 Hz, 3J(H,P) = 6.0 Hz, C6H4', o to P, 2H), 7.65-7.55 (m, o-C6H5,

6H), 7.11-6.95 (m, m-, p-C6H5, 9H), 6.72 (d, 3J(H,H) = 8.6 Hz, C6H4, m to P, 2H), 6.60 (d, 3J(H,H)

= 8.6 Hz, C6H4', m to P, 2H), 4.63 (s, C5H5, 5H), 2.94 (dd, 2J(H,H) = 11.5 Hz, J(H,P) = 9.7 Hz,

CHH', 1H), 2.52, 2.50 (2 s, CH3 and CH3', 2 × 6H), 2.25 (dd, 2J(H,H) = 11.5 Hz, J(H,P) = 2.5 Hz,

CHH', 1H); 13C{1H} NMR (76 MHz, C6D6, δ in ppm): 89.9 (s, C5H5), –16.6 (dd, 1J(C,P) = 36.6

Hz, 2J(C,P) = 4.8 Hz CHH'); PPh3 at 136.8 (d, 1J(C,P) = 50.9 Hz, i), 134.1 (d, 2J(C,P) = 10.4 Hz, o),

130.0 (d, 4J(C,P) = 1.6 Hz, p), 128.5 (d, 3J(C,P) = 10.0 Hz, m); P(C6H4N(CH3)2)(C6H4N(CH3)2)'

at 150.5, 150.2 (2 s, p and p' to P), 134.8 (d, 1J(C,P) = 19.8 Hz, i to P), 133.9 (d, 1J(C,P) = 18.4 Hz,

i' to P), 134.4 (s (other line of expected d obscured), o to P), 133.8 (d, 2J(C,P) = 15.9 Hz, o' to P),

113.0 (d, 3J(C,P) = 6.0 Hz, m to P), 112.7 (d, 3J(C,P) = 7.1 Hz, m' to P), 40.4, 40.3 (2 s, CH3 and

CH3'); 31P{1H} NMR (121 MHz, C6D6, δ in ppm): 27.2 (d, 3J(P,P) = 6.7 Hz, PPh3), 2.8 (d, 3J(P,P)

= 6.7 Hz, P(p-C6H4N(CH3)2)2).

IR (thin film, cm–1):71 1633 (s, νNO). MS:92 830 (51) [14d]+, 558 (100) [14d–P(p-

C6H4N(CH3)2)2H]+.

(S)-(η5-C5H5)Re(NO)(PPh3)(CH2P(p-C6H4N(CH3)2)2 ((S)-14d). (S)-[14d-H]+ PF6–

(0.196 g, 0.201 mmol), t-BuOK (0.0338 g, 0.302 mmol), and C6H6 (20 mL) were combined in a

procedure analogous to that given for the racemate. An identical workup gave (S)-14d as a red


powder (0.149 g, 0.179 mmol, 89%). M.p. 130-135 °C, dec. (capillary). Spectroscopic data were

similar to those of the racemate.

[(η5-C5H5)Re(NO)(PPh3)(CH2P(2-biphen)2H)]+ PF6– ([14e-H]+ PF6

–). A Schlenk flask

was charged with racemic 26 (0.212 g, 0.380 mmol)82 and CH2Cl2 (15 mL). The solution was

cooled to –78 °C and Ph3C+ PF6– (0.162 g, 0.418 mmol) was added with stirring. After 1 h, P(2-

biphen)2H (28e, 0.167 g, 0.494 mmol) dissolved in CH2Cl2 (1.5 mL) was added dropwise. After 20

min, the cold bath was removed. After 1 h, the sample was concentrated by oil pump vacuum (to ca.

4 mL). A CH3OH/EtOH mixture (4 mL, 1:1 v/v) was added. The solution was added dropwise to

vigorously stirred hexanes (75 mL). The precipitate was collected by filtration, washed with

hexanes (3 × 3 mL), and dried by oil pump vacuum to give [14e-H]+ PF6– as an orange powder

(0.376 g, 0.361 mmol, 95%). M.p. 236 °C, dec. (capillary). Elemental analysis calcd (%) for

C48H41F6NOP3Re (1041.2): C 55.38, H 3.97, N 1.35; found: C 55.28, H 4.05, N 1.37.

1H NMR (400 MHz, CD2Cl2, δ in ppm): 7.79-7.67, 7.62-7.35, 7.26-7.17, 7.11-7.00 (4 m,

aryl-H, 33H), 6.48 (dd (other part of expected ddd obscured), 3J(H,H) = 12.4 Hz, 3J(H,H') 3.1 Hz,

PH, 0.5H), 4.46 (s, C5H5, 5H), 2.30-2.16 (m, CHH', 1H), 1.61-1.50 (m, CHH', 1H); 13C{1H} NMR

(101 MHz, CD2Cl2, δ in ppm): 90.7 (s, C5H5), –30.9 (dd, 1J(C,P) = 28.8 Hz, 2J(C,P) = 3.8 Hz,

CHH'); PPh3 at 134.4 (d, 1J(C,P) = 53.7 Hz, i), 133.8 (d, 2J(C,P) = 10.7 Hz, o), 131.6 (d, 4J(C,P) =

1.9 Hz, p), 129.4 (d, 3J(C,P) = 10.7 Hz, m); P(2-biphen)(2-biphen)' at93 147.8, (d, J(C,P) = 6.5 Hz),

146.6 (d, J(C,P) = 9.2 Hz), 139.6 (d, J(C,P) = 5.0 Hz), 139.5 (d, J(C,P) = 4.6 Hz), 134.3 (d, J(C,P)

= 2.3 Hz), 134.0 (d, J(C,P) = 2.7 Hz), 133.5 (d, J(C,P) = 10.7 Hz), 132.7 (d, J(C,P) = 10.0 Hz),

132.4 (d, J(C,P) = 8.8 Hz), 132.1 (d, J(C,P) = 8.1 Hz), 129.78, 129.76, 129.7, 129.5, 129.4 (5 s),

129.2 (d, J(C,P) = 10.7 Hz), 128.7 (d, J(C,P) = 11.9 Hz), 125.4 (d, 1J(C,P) = 65.2 Hz, i to P), 118.7

(d, 1J(C,P) = 87.4 Hz, i' to P); 31P{1H} NMR (162 MHz, CD2Cl2, δ in ppm): 24.0 (d, 3J(P,P) =

20.8 Hz, PH), 20.5 (d, 3J(P,P) = 20.8 Hz, PPh3), –142.9 (sept, 1J(P,F) = 708 Hz, PF6).

IR (thin film, cm–1):71 1660 (s, νNO). MS:92 896 (80) [14e-H]+, 558 (100) [14e–P(2-

biphen)2H]+.

(η5-C5H5)Re(NO)(PPh3)(CH2P(2-biphen)2) (14e). A Schlenk flask was charged with


racemic [14e-H]+ PF6– (0.520 g, 0.500 mmol) and C6H6 (30 mL). The suspension was vigorously

stirred and solid t-BuOK (0.0840 g, 0.749 mmol) was added. After 1 h, the orange suspension was


The filtrate was concentrated by oil pump vacuum to ca. 5 mL and layered with n-pentane (35 mL).

The orange precipitate was collected by filtration and dried by oil pump vacuum to give pure 14e

(0.406 g, 0.453 mmol, 91%). Dec. pt. 205 °C (capillary). Elemental analysis calcd (%) for

C48H40NOP2Re (895.2): C 64.42, H 4.50, N 1.57; found: C 64.15, H 4.11, N 1.64.

1H NMR (400 MHz, CD2Cl2, δ in ppm): 7.41-7.33, 7.31-7.20, 7.14-6.98 (3 m, aryl-H, 32H),

4.39 (s, C5H5, 5H), 1.89 (apparent dt, 2J(H,H) = 12.6 Hz, 2J(H,P) = 3J(H,P) = 8.6 Hz, CHH', 1H),

1.32 (ddd, 2J(H,H) = 12.6 Hz, 2J(H,P) = 8.6 Hz, 3J(H,P) = 2.5 Hz, CHH', 1H); 13C{1H} NMR (76

MHz, CD2Cl2, δ in ppm): 90.9 (dd, 2J(C,P) = 4.4 Hz, 3J(C,P) = 1.2 Hz, C5H5), –16.3 (dd, 1J(C,P) =

39.6 Hz, 2J(C,P) = 5.1 Hz, CHH'); PPh3 at 136.7 (d, 1J(C,P) = 51.4 Hz, i), 134.1 (d, 2J(C,P) = 10.5

Hz, o), 130.5 (d, 4J(C,P) = 2.0 Hz, p), 128.8 (d, 3J(C,P) = 10.1 Hz, m); P(2-biphen)(2-biphen)' at93

149.2, 149.2, 148.8, 148.7, 146.5, 146.2, 144.3, 144.2, 144.0, 144.0, 139.8, 139.6, 135.8, 135.7,

131.3, 131.0, 131.0, 130.7, 130.7, 130.5, 130.4, 130.4, 130.3, 128.2, 128.1, 127.4, 127.3, 127.0,

126.9, 126.7; 31P{1H} NMR (162 MHz, CD2Cl2, δ in ppm): 24.6 (d, 3J(P,P) = 6.9 Hz, PPh3), –5.7

(d, 3J(P,P) = 6.9 Hz, P(2-biphen)2).

IR (thin film, cm–1):71 1621 (s, νNO). MS:92 m/z (%): 896 (80) [14e-H]+, 558 (100) [14e–

P(2-biphen)2]+.

[(η5-C5H5)Re(NO)(PPh3)(CH2P(α-naph)2H)]+ PF6– ([14f-H]+ PF6

–). A Schlenk flask

was charged with racemic 26 (0.500 g, 0.896 mmol)82 and CH2Cl2 (25 mL). The solution was

cooled to –78 °C and Ph3C+ PF6– (0.382 g, 0.986 mmol) was added with stirring. After 1 h, P(α-

naph)2H (28f, 0.308 g, 1.075 mmol) dissolved in CH2Cl2 (5 mL) was added. After 20 min, the cold

bath was removed. After 1 h, the sample was concentrated by oil pump vacuum (to ca. 4 mL). A

CH3OH/EtOH mixture (4 mL, 1:1 v/v) was added. Then hexanes (ca. 20 mL) were added dropwise

with vigorous stirring. The precipitate was collected by filtration, washed with hexanes (3 × 3 mL),

and dried by oil pump vacuum to give [14f-H]+ PF6– as an orange powder (0.772 g, 0.781 mmol,

87%). Dec. pt. 181-183 °C (capillary). Elemental analysis calcd (%) for C44H37F6NOP3Re (989.2):


C 53.44, H 3.77, N 1.42; found: C 53.20, H 3.72, N 1.39.

1H NMR (400 MHz, CD2Cl2, δ in ppm): 6.48 (dd (other part of expected ddd obscured),

3J(H,H) = 12.3 Hz, 3J(H,H') = 3.0 Hz, PH, 0.5H), 8.45 (dd, 3J(H,P) = 17.3 Hz, 3J(H,H) = 7.1 Hz, 2-

C10H7, 1H), 8.34 (dd, 3J(H,P) = 16.0 Hz, 3J(H,H) = 7.2 Hz, 2-C10H7', 1H), 8.25, 8.17, 8.12, 8.02,

7.95, 7.82 (6 d, 3J(H,H) = 8.2, 8.4, 8.4, 8.0, 8.0, and 8.3 Hz, 4-, 5-, 8-C10H7 and 4-, 5-, 8-C10H7', 6

× 1H), 7.80-7.71, 7.69-7.60 (2 m, 6-, 7-C10H7 and 6-, 7-C10H7', 2 × 2H), 7.55 (apparent t, 3J(H,H)

= 7.0 and 7.0 Hz, 3-C10H7, 1H), 7.49 (apparent t, 3J(H,H) = 7.2 and 7.2 Hz, 3-C10H7', 1H), 7.47-

7.31 (m, C6H5, 15H), 4.62 (s, C5H5, 5H), 3.06-2.96, 2.87-2.74 (2 m, CHH', 2 × 1H); 13C{1H}

NMR (101 MHz, CD2Cl2, δ in ppm): 90.6 (s, C5H5), –33.9 (d, 1J(C,P) = 27.4 Hz, CHH'); PPh3 at

134.1 (d, 1J(C,P) = 54.8 Hz, i), 133.8 (d, 2J(C,P) = 10.5 Hz, o), 131.4 (d, 4J(C,P) = 2.1 Hz, p),

129.4 (d, 3J(C,P) = 10.5 Hz, m); P(α-naph)(α-naph)' at93 135.8 (d, J(C,P) = 2.9), 135.6 (d, J(C,P) =

2.9 Hz), 135.5 (d, J(C,P) = 10.5 Hz), 135.2 (d, J(C,P) = 11.8 Hz), 134.0 (d, J(C,P) = 4.6 Hz), 133.9

(d, J(C,P) = 3.4 Hz), 132.8 (d, J(C,P) = 8.4 Hz), 132.3 (d, J(C,P) = 5.9 Hz), 130.4, 130.2, 129.6,

128.8, 128.1, 127.5 (6 s), 126.0 (d, J(C,P) = 11.4 Hz), 125.9 (d, J(C,P) = 11.4 Hz), 124.1 (d, J(C,P)

= 8.0 Hz), 123.5 (d, J(C,P) = 8.0 Hz), 120.5 (d, 1J(C,P) = 65.3 Hz, 1-C10H7), 119.6 (d, 1J(C,P) =

83.5 Hz, 1-C10H7'); 31P{1H} NMR (162 MHz, CD2Cl2, δ in ppm): 22.7 (d, 3J(P,P) = 12.9 Hz, PH),

20.3 (d, 3J(P,P) = 12.9 Hz, PPh3), –142.9 (sept, 1J(P,F) = 708 Hz, PF6).

IR (thin film, cm–1):71 1656 (s, νNO). MS:92 844 (45) [14f-H]+, 558 (100) [14f–P(α-

naph)2H]+.

(η5-C5H5)Re(NO)(PPh3)(CH2P(α-naph)2) (14f). A Schlenk flask was charged with [14f-

H]+ PF6– (0.361 g, 0.365 mmol) and C6H6 (22 mL). The suspension was vigorously stirred and

solid t-BuOK (0.0613 g, 0.548 mmol) was added. After 1 h, the orange suspension was filtered

through a plug of Celite®. The plug was rinsed with C6H6 until the filtrate became colorless. The

filtrate was concentrated by oil pump vacuum (to ca. 5 mL), and n-pentane (35 mL) was added

dropwise with vigorous stirring. The precipitate was collected by filtration and dried by oil pump

vacuum to give 14f as a pale yellow powder (0.197 g, 0.234 mmol, 64%). M.p. 187-189 °C, dec.

(capillary). Elemental analysis calcd (%) for C44H36NOP2Re (843.2): C 62.70, H 4.30, N 1.66;

found: C 62.80, H 4.50, N 1.76.


1H NMR (400 MHz, CD2Cl2, δ in ppm): 8.87-8.82, 8.78-8.72, 7.82-7.69, 7.52-7.28 (4 m,

aryl-H, 29H), 4.62 (s, C5H5, 5H), 2.63 (dd, 2J(H,H) = 11.5 Hz, J(H,P) = 9.6 Hz, CHH', 1H), 1.91 (d,

2J(H,H) = 11.5 Hz, CHH', 1H); 13C{1H} NMR (76 MHz, CD2Cl2, δ in ppm): 90.4 (s, C5H5), –19.1

(dd, 1J(C,P) = 36.8 Hz, 2J(C,P) = 4.8 Hz, CHH'); PPh3 at 136.3 (d, 1J(C,P) = 51.9 Hz, i), 134.2 (d,

2J(C,P) = 10.4 Hz, o), 130.7 (d, 4J(C,P) = 2.1 Hz, p), 128.9 (d, 3J(C,P) = 10.1 Hz, m); P(α-naph)(α-

naph)' at93 145.9, 145.5, 143.5, 143.2, 136.5, 136.5, 136.3, 136.2, 134.2, 133.9, 133.8, 130.8, 130.3,

129.1, 128.4, 128.4, 127.6, 127.3, 127.2, 126.9, 126.1, 126.0, 125.8, 125.8, 125.7; 31P{1H} NMR

(162 MHz, CD2Cl2, δ in ppm): 26.5 (d, 3J(P,P) = 6.9 Hz, PPh3), –21.2 (d, 3J(P,P) = 6.9 Hz, P(α-

naph)2).

IR (thin film, cm–1):71 1644 (s, νNO). MS:92 842 (30) [14f–H]+, 558 (100) [14f–P(α-

naph)2]+.

(SReSC)-[(η5-C5H5)Re(NO)(PPh3)(CHCH3PPh2H)]+ PF6– ((SReSC)-[15b-H]+ PF6

–). A

Schlenk flask was charged with (S)-(η-C5H5)Re(NO)(PPh3)(CH2CH3) (0.114 g, 0.199 mmol)89 and

CH2Cl2 (5 mL). The solution was cooled to –78°C and Ph3C+ PF6– (0.0722 g, 0.219 mmol) was

added with stirring. After 1 h, the orange mixture had turned bright yellow. Then PPh2H (0.0555 g,

0.299 mmol) dissolved in CH2Cl2 (0.6 mL) was added. After 1 h, the mixture was allowed to

slowly warm to room temperature over the course of 1 h. The solution was concentrated (to ca. 1

mL) and n-pentane was added. The oil-like precipitate was isolated by decantation and dissolved in

CH2Cl2/t-BuOH (7 mL, 2:5 v/v). The solvent was concentrated by oil pump vacuum with vigorous

stirring and a yellow powder precipitated, which was collected by filtration, washed with n-pentane

(2 × 0.5 mL), and dried by oil pump vacuum to give (SReSC)-[15b-H]+ PF6–as a pale yellow

powder (0.0920 g, 55%). Dec. pt. 125-128 °C (capillary). Elemental analysis calcd (%) for

C37H35F6NOP3Re (902.8): C 49.22, H 3.91, N 1.55; found: C 49.17, H 4.06, N 1.52. [α]25589 =

105° ± 1° (c = 1.00 mg/mL, CH2Cl2).

1H NMR (400 MHz, CDCl3, δ in ppm): 7.79-7.30 (m, C6H5, 25H), 7.48 (dd, 1J(H,P) = 493

Hz, 3J(H,H) = 9.0 Hz, PH, 1H), 5.06 (s, C5H5, 5H), 3.46-3.35 (m, CHCH3, 1H), 1.27 (dd, J(H,P) =

24.5 Hz, 3J(H,H) = 7.5 Hz, CHCH3, 3H); 13C{1H} NMR (76 MHz, CD2Cl2, δ in ppm; the ReCH

signal was not observed): 91.6 (s, C5H5); PPh3 at 133.9 (d, 1J(C,P) = 54.0 Hz, i), 133.7 (d, 2J(C,P)


= 10.6 Hz, o), 131.5 (d, 4J(C,P) = 2.2 Hz, p), 129.5 (d, 3J(C,P) = 10.4 Hz, m); PPhPh' at 134.6 (d,

4J(C,P) = 2.6 Hz, p to P), 134.1 (d, 4J(C,P) = 2.6 Hz, p' to P), 133.2 (d, 2J(C,P) = 9.1 Hz, o to P),

132.6 (d, 2J(C,P) = 9.1 Hz, o' to P), 130.5 (d, 3J(C,P) = 11.5 Hz, m to P), 130.3 (d, 3J(C,P) = 11.7

Hz, m' to P), 122.4 (d, 1J(C,P) = 57.7 Hz, i to P), 121.5 (d, 1J(C,P) = 68.1 Hz, i' to P), 20.4 (s, CH3);

31P{1H} NMR (122 MHz, CD2Cl2, δ in ppm): 22.7 (d, 3J(P,P) = 14.9 Hz, PPh3), 31.9 (d, 3J(P,P) =

14.6 Hz, PH), –142.8 (sept, 1J(P,F) = 713 Hz, PF6).

IR (thin film, cm–1):71 1668 (s, νNO). MS:92 758 (18) [15b-H]+, 572 (100) [15b–PPh2H]+.

(SReSP)/(SReRP)-[(η5-C5H5)Re(NO)(PPh3)(CH2PPh(α-naph)H)]+ PF6– ((SReSP)/

(SReRP)-[17c-H]+ PF6–). A Schlenk flask was charged with (S)-26 (0.200 g, 0.358 mmol)82 and

CH2Cl2 (20 mL). The solution was cooled to –78 °C and Ph3C+ PF6– (0.153 g, 0.394 mmol) was

added with stirring. After 1 h, PPh(α-naph)H (29c, 0.126 g, 0.537 mmol) dissolved in CH2Cl2 (1

mL) was added. After 3 h, the mixture was allowed to slowly warm to room temperature over the

course of 1 h. The mixture was concentrated by oil pump vacuum (to ca. 7 mL) and n-pentane (10

mL) was added dropwise with stirring. A first crop of (SReSP)/(SReRP)-[17c-H]+ PF6– precipitated

as a yellow powder (0.148 g, 0.152 mmol, 72% de, 43%), which was collected by filtration and

dried by oil pump vacuum. The yellow powder was dissolved in CH2Cl2 (8 mL) and n-pentane (8

mL) was slowly added dropwise with vigorous stirring. The (SReSP)/(SReRP)-[17c-H]+ PF6– was

similarly isolated. Several such cycles may be necessary to obtain (SReSP)/(SReRP)-[17c-H]+ PF6–

with a high diastereomeric excess (best result for diastereomer 1: 94% de, absolute configuration

not assigned). The supernatant from the first crop was treated with n-pentane (15 mL) with stirring.

A yellow powder precipitated, which was collected by filtration and dried by oil pump vacuum to

give diastereomer 2 (0.120 g, 0.124 mmol, –92% de, 35%).

Analytical data for diastereomer 1 (94% de): Elemental analysis calcd (%) for

C40H35F6NOP3Re.(CH2Cl2)0.33 (967.1): C 50.09, H 3.72, N 1.45; found: C 50.40, H 3.71, N 1.41.

1H NMR (400 MHz, CD3CN, δ in ppm): aryl-H at 8.28 (d, J = 8.3 Hz, 1H), 8.18-8.03 (m,

2H), 7.84-7.23 (m, 24H); 7.88 (dt, 1J(H,P) = 497 Hz, 3J(H,H) = 8.1 Hz, PH, 1H), 5.32 (CH2Cl2),

5.05 (s, C5H5, 5H), 2.80-2.47 (m, CHH', 2H); 13C{1H} NMR (76 MHz, CD3CN, δ in ppm): 91.7 (d,

2J(C,P) = 1.4 Hz, C5H5); PPh3 at 135.0 (d, 1J(C,P) = 53.5 Hz, i), 134.2 (d, 2J(C,P) = 10.4 Hz, o),


131.8 (d, 4J(C,P) = 2.5 Hz, p), 129.8 (d, 3J(C,P) = 10.4 Hz, m); P(α-naph)Ph at93,94 136.5, 136.3,

136.05, 136.01, 134.79, 134.75, 133.0 (d, J(C,P) = 10.4 Hz), 130.7, 130.6, 129.8, 129.4, 128.2,

126.5, 126.3, 125.9, 125.1, 125.0, 124.9; 31P{1H} NMR (162 MHz, CD3CN, δ in ppm): 28.3 (d,

3J(P,P) = 17.1 Hz, PH), 22.1 (d, 3J(P,P) = 17.1 Hz, PPh3), –143.2 (sept, 1J(P,F) = 707 Hz, PF6).

IR (thin film, cm–1):71 1644 (s, νNO). MS:95 792 (100) [17c]+, 558 (62) [17c–PPh(α-

naph)H]+.

Analytical data for diastereomer 2 (–92% de): Elemental analysis calcd (%) for

C40H35F6NOP3Re.(CH2Cl2)0.33 (967.1): C 50.09, H 3.72, N 1.45; found: C 50.35, H 3.67, N 1.49.

1H NMR (400 MHz, CD3CN, δ in ppm): aryl-H at 8.38-8.23 (m, 2H), 8.13 (d, J = 7.9 Hz,

1H), 7.89-7.27 (m, 24H); 7.80 (ddd, 1J(H,P) = 500 Hz, 3J(H,H) = 9.8 and 6.7 Hz, PH, 1H), 5.32

(CH2Cl2), 4.84 (s, C5H5, 5H), 2.86-2.71 (m, CHH', 1H), 2.61-2.44 (m, CHH', 1H); 13C{1H} NMR

(76 MHz, CD2Cl2, δ in ppm): 90.5 (s, C5H5), –35.8 (d, 2J(C,P) = 27.2 Hz, CH2); aryl-C at93 136.4,

136.32, 136.30, 134.6, 134.31, 134.29, 134.2, 134.0 (d, 2J(C,P) = 10.4 Hz, o-PPh3), 133.8, 132.5,

132.4, 132.1, 132.0, 131.7, 131.6, 131.5, 131.5, 130.7, 130.4, 130.2, 129.8, 129.6 (d, 3J(C,P) = 10.7

Hz, m-PPh3), 129.4, 128.4, 126.1, 125.9, 125.2, 124.7, 124.6, 124.3, 118.4, 117.3; 31P{1H} NMR

(162 MHz, CD2Cl2, δ in ppm): 29.0 (d, 3J(P,P) = 12.6 Hz, PH), 22.3 (d, 3J(P,P) = 12.6 Hz, PPh3), –

143.9 (sept, 1J(P,F) = 709 Hz, PF6).

IR (thin film, cm–1):71 1652 (s, νNO). MS:95 792 (100) [17c]+, 558 (32) [17c–PPh(α-

naph)H]+.

(SReSP)/(SReRP)-[(η5-C5H5)Re(NO)(PPh3)(CH2PPh(α-naph)) ((SReSP)/(SReRP)-17c). A

Schlenk flask was charged with (SReSP)/(SReRP)-[17c-H]+ PF6– (each 0.160 g, 0.172 mmol,

diastereomer 1: 94% de; diastereomer 2: –92% de) and C6H6 (20 mL). The suspension was stirred

and t-BuOK (0.0288 g, 0.257 mmol) was added. After 1 h, the orange suspension was filtered

through a plug of Celite®. The plug was rinsed with C6H6 until the filtrate became colorless. The

filtrate was concentrated by oil pump vacuum (to ca. 2 mL), layered with n-pentane (15 mL), and

kept at 4 °C. After 48 h, an orange solid precipitated, which was collected by filtration and dried by

oil pump vacuum to give (SReSP)/(SReRP)-17c (diastereomer 1: 0.0868 g, 0.110 mmol, 94% de,

64%; diastereomer 2: 0.0709 g, 0.0894 mmol, –92% de, 52%).


Analytical data for diastereomer 1 (94% de): 1H NMR (300 MHz, CD2Cl2, δ in ppm):

aryl-H at 8.61-8.55 (m, 1H), 7.81-7.72 (m, 2H), 7.62-7.57 (m, 1H), 7.49-7.31 (m, 20H), 7.21-7.13

(m, 3H); 4.71 (s, C5H5, 5H), 2.47 (apparent t, 2J(H,H) = J(H,P) = 10.5 Hz, CHH', 1H), 1.98 (dd,

2J(H,H) = 10.5 Hz, J(H,P) = 1.99 Hz, CHH', 1H); 31P{1H} NMR (121 MHz, CD2Cl2, δ in ppm):

26.3 (d, 3J(P,P) = 7.4 Hz, PPh3), –6.7 (d, 3J(P,P) = 7.4 Hz, PPh(α-naph)).

Analytical data for diastereomer 2 (–92% de): 1H NMR (400 MHz, CD2Cl2, δ in ppm):

aryl-H at 8.70-8.65 (m, 1H), 7.83-7.75 (m, 2H), 7.62-7.59 (m, 1H), 7.47-7.31 (m, 20H), 7.21-7.14

(m, 3H); 4.71 (s, C5H5, 5H), 2.55 (apparent t, 2J(H,H) = J(H,P) = 12.0 Hz, CHH', 1H), 1.86 (dd,

2J(H,H) = 12.0 Hz, J(H,P) = 2.1 Hz, CHH', 1H); 31P{1H} NMR (121 MHz, CD2Cl2, δ in ppm):

26.4 (d, 3J(P,P) = 6.9 Hz, PPh3), –4.0 (d, 3J(P,P) = 6.9 Hz, PPh(α-naph)).

(SReSP)/(SReRP)-[(η5-C5H5)Re(NO)(PPh3)(CH2PPh(β-naph)H)]+ PF6– ((SReSP)/

(SReRP)-[17d-H]+ PF6–). A Schlenk flask was charged with (S)-26 (0.200 g, 0.358 mmol)82 and

CH2Cl2 (20 mL). The solution was cooled to –78 °C and Ph3C+ PF6– (0.153 g, 0.394 mmol) was

added with stirring. After 1 h, PPh(β-naph)H (29d, 0.126 g, 0.537 mmol) dissolved in CH2Cl2 (1

mL) was added dropwise. After 3 h, the cold bath was removed. After 1 h, the mixture was

concentrated by oil pump vacuum (to ca. 5 mL) and diethyl ether (10 mL) was added dropwise. A

yellow powder precipitated, which was collected by filtration and dried by oil pump vacuum to give

(SReSP)/(SReRP)-[17d-H]+ PF6– (0.280 g, 0.298 mmol, 83%) as a 50:50 mixture of diastereomers.

Elemental analysis calcd (%) for C40H35F6NOP3Re.(CH2Cl2)0.33 (967.1): C 50.09, H 3.72, N 1.45;

found: C 50.12, H 3.90, N 1.37.

1H NMR (300 MHz, CD2Cl2, δ in ppm): 8.49 (d (other part of expected ddd obscured),

3J(H,H) = 16.1 Hz, ½ PH, 0.25H), 8.16-7.23 (m, aryl-H and ½ PH, 27.5H), 6.43 (d (other part of

expected ddd obscured), 3J(H,H) = 12.5 Hz, ½ PH, 0.25H), 4.91, 4.87 (2 s, 2 C5H5, 5H), 2.78-2.63,

2.58-2.40 (2 m, CHH', 2H); 13C{1H} NMR (101 MHz, CD2Cl2, δ in ppm): 91.1, 90.0 (2 d, 2J(C,P)

= 1.1 and 1.4 Hz, 2 C5H5), –35.5 (d, 1J(C,P) = 32.1 Hz, CHH'); PPh3 at 134.3 (d, 1J(C,P) = 54.1 Hz,

i), 134.0 (d, 2J(C,P) = 10.6 Hz, o), 131.6 (d, 4J(C,P) = 2.1 Hz, p), 129.6 (d, 3J(C,P) = 10.5 Hz, m),

PPh(β-naph) at93 135.8, 135.7, 134.9, 134.9, 134.8, 133.9, 133.2, 132.8, 132.6, 132.1, 132.0, 130.6,

130.4, 130.3, 130.2, 130.0, 129.4, 128.7, 128.5, 125.6, 125.5, 123.5, 122.3, 122.1, 121.2; 31P{1H}


NMR (121 MHz, CD2Cl2, δ in ppm): 30.2, 29.7 (2 d, 3J(P,P) = 12.6 and 11.9 Hz, 2 PH), 21.6, 21.5

(2 d, 3J(P,P) = 11.9 and 12.6 Hz, 2 PPh3), –143.9 (sept, 1J(P,F) = 711.4 Hz, PF6).

IR (thin film, cm–1):71 1652 (s, νNO). MS:95 793 (60) [17d-H]+, 558 (100) [17d–PPh(β-

naph)H]+.

(SReSP)/(SReRP)-(η5-C5H5)Re(NO)(PPh3)(CH2PPh(β-naph)) ((SReSP)/(SReRP)-17d). A

Schlenk flask was charged with (SReSP)/(SReRP)-[17d-H]+ PF6– (0.200 g, 0.213 mmol, 50:50

diastereomer mixture) and C6H6 (20 mL). The suspension was vigorously stirred and t-BuOK

(0.0358 g, 0.320 mmol) was added. After 1 h, the orange suspension was filtered through a plug of

Celite®. The plug was rinsed with C6H6 until the filtrate became colorless. The filtrate was

concentrated by oil pump vacuum (to ca. 4 mL), layered with n-pentane (10 mL), and kept at 4 °C.

After 168 h, a dark red solid had precipitated, which was collected by filtration and dried by oil

pump vacuum to give (SReSP)/(SReRP)-17d (0.0868 g, 0.110 mmol, 26%) as a 74:26 mixture of

diastereomers 1/2 (48% de). The C6H6/n-pentane filtrate was treated with a large excess of n-

pentane. The precipitate was collected by filtration and dried by oil pump vacuum to give

(SReSP)/(SReRP)-17d (0.0709 g, 0.0894 mmol, 21%) as a 4:96 mixture of diastereomer 1/2 (–92%

de).

Analytical data for diastereomer 1 (48% de): 1H NMR (300 MHz, CD2Cl2, δ in ppm):

aryl-H at 8.01, 7.92 (2 d, 3J(H,H) = 7.1 Hz, together 1H (27:73)), 7.82-7.64 (m, 3H), 7.26-7.19 (m,

25H); 4.78, 4.76 (2 s, C5H5, together 5H (74:26)), 2.58-2.45 (m, CHH', 1H), 2.02-1.91 (m, CHH',

1H). 31P{1H} NMR (121 MHz, CD2Cl2, δ in ppm): 27.8 (d, 3J(P,P) = 7.4 Hz, PPh3), 9.11 (d,

3J(P,P) = 7.4 Hz, PPh(β-naph)).

Analytical data for diastereomer 2 (–92% de): 1H NMR (300 MHz, CD2Cl2, δ in ppm):

aryl-H at 7.99 (d, 3J(H,H) = 7.1 Hz, 1H), 7.81-7.73 (m, 2H), 7.69 (d, 3J(H,H) = 8.3 Hz, 1H), 7.52-

7.16 (m, 25H); 4.76 (s, C5H5, 5H), 2.48 (dd, 2J(H,H) = 12.2 Hz, J(H,P) = 9.9 Hz, CHH', 1H), 1.98

(dd, 2J(H,H) = 12.2 Hz, J(H,P) = 2.4 Hz, CHH', 1H); 31P{1H} NMR (121 MHz, CD2Cl2, δ in ppm):

27.6 (d, 3J(P,P) = 6.7 Hz, PPh3), 9.51 (d, 3J(P,P) = 6.7 Hz, PPh(β-naph)).


3.4.3 Preparation of Secondary Phosphines

P(2-biphen)2H (28e). A Grignard reagent was prepared from Mg (0.3360 g, 13.99 mmol)

and 2-biphenylbromide (2.964 g, 12.72 mmol) in THF (40 mL). Then THF (40 mL) was added, but

some white precipitate remained undissolved. A solution of PCl3 (0.8314 g, 6.025 mmol) in THF

(30 mL) was cooled to –78 °C. The Grignard mixture was added dropwise with stirring over 2 h.

The solution was allowed to warm to room temperature overnight. It was then cooled to 0 °C, and

LiAlH4 (0.2290 g, 6.025 mmol) was added carefully with vigorous stirring (evolving gas). After 5

min, freshly degassed aqueous NaOH (2 N, 12 mL) was added. The organic phase was separated

and filtered through a plug of silica gel. The plug was rinsed with THF (30 mL). The solvent was

removed from the filtrate by oil pump vacuum. The residue was dissolved in a minimum of CH2Cl2.

This solution was layered with n-pentane and kept at 4 °C. After 168 h, the white precipitate was

collected by filtration and dried by oil pump vacuum to give 28e as a white solid (1.425 g, 4.218

mmol, 70%).

1H NMR (400 MHz, CDCl3, δ in ppm): 7.40-7.12 (m, aryl-H, 18H), 4.61 (br s, PH, 1H);

13C{1H} NMR (76 MHz, CDCl3, δ in ppm):93 aryl-C at 146.9 (d, J(C,P) = 15.9 Hz), 144.9 (d,

J(C,P) = 3.2 Hz), 135.5 (d, J(C,P) = 10.3 Hz), 133.9 (d, J(C,P) = 14.6 Hz), 129.8 (d, J(C,P) = 2.8

Hz), 129.1 (d, J(C,P) = 3.0 Hz), 128.3, 127.8, 127.2, 127.1 (4 s); 31P{1H} NMR (162 MHz, CDCl3,

δ in ppm): –53.3 (s).

P(α-naph)2H (28f). A Grignard reagent was prepared from Mg (1.217 g, 50.00 mmol) and

α-naphthylbromide (10.35 g, 50.00 mmol) in THF (60 mL). Then THF (30 mL) was added. A

solution of PCl3 (3.136 g, 22.70 mmol) in THF (30 mL) was prepared and cooled to 0 °C. The

Grignard solution was added dropwise with stirring over 2 h. The mixture was allowed to warm to

room temperature overnight, and was filtered through a plug of Celite®. The filtrate was then

cooled to 0 °C, and LiAlH4 (1.670g, 22.70 mmol) was added carefully with vigorous stirring

(evolving gas). After 5 min, freshly degassed aqueous NaOH (2 N, 10 mL) was added. The organic

phase was separated and filtered through a plug of silica gel. The solvent was removed from the


filtrate by oil pump vacuum. The residue was distilled twice (Kugelrohr, 2 × 10–2 mbar, first

distillation 280-300 °C, second distillation 265-270 °C). The distillate was crystallized from a very

concentrated solution in CH2Cl2. White crystals were collected by filtration and dried by oil pump

vacuum to give 28f (2.000 g, 7.840 mmol, 35%). Analytical data agreed with that in the literature.88

PPh(α-naph)H (29c). A Grignard reagent was prepared from Mg (1.217 g, 50.00 mmol)

and α-naphthylbromide (10.35 g, 50.00 mmol) in THF (50 mL). Then THF (50 mL) was added. A

solution of PPhCl2 (8.136 g, 45.45 mmol) in THF (160 mL) was cooled to –78 °C. The Grignard

solution was added dropwise with stirring over 2 h. The solution was allowed to warm to room

temperature overnight. It was then cooled to 0 °C, and LiAlH4 (2.073 g, 54.54 mmol) was carefully

added with vigorous stirring (evolving gas). After 30 min, freshly degassed aqueous NaOH (2 N, 10

mL) was added. After 1 h, the organic phase was filtered through a plug of silica gel topped with a

plug of Celite®. The plugs were rinsed with THF (50 mL). The solvent was removed from the

filtrates by oil pump vacuum. The residue was distilled (Kugelrohr, 6.6 × 10–3 mbar, 185-200 °C)

to give 29c as a colorless liquid (4.537 g, 19.23 mmol, 42%).

1H NMR (400 MHz, CDCl3, δ in ppm): aryl-H at 8.29-8.24 (m, 1H), 7.90-7.85 (m, 2H),

7.68 (t, J = 7.2 Hz, 1H), 7.53-7.46 (m, 4H), 7.43 (t, J = 7.5 Hz, 1H), 7.33-7.27 (m, 3H); 5.53 (br s,

PH, 1H); 13C{1H} NMR (101 MHz, CDCl3, δ in ppm):93 134.9, 134.8, 134.2, 134.1, 133.9, 133.9,

133.8, 133.6, 133.6, 132.1, 132.0, 129.8, 128.8, 128.6, 128.5, 128.5, 126.5, 126.4, 126.2, 126.0,

125.6, 125.5; 31P{1H} NMR (162 MHz, CDCl3, δ in ppm): –50.0 (s).

PPh(β-naph)H (29d). A Grignard reagent was prepared from Mg (1.217 g, 50.00 mmol)

and β-naphthylbromide (10.35 g, 50.00 mmol) in THF (50 mL). Then THF (50 mL) was added. A

solution of PPhCl2 (8.136 g, 45.45 mmol) in THF (160 mL) was cooled to –78 °C. The Grignard

solution was added dropwise with stirring over 2 h. The mixture was allowed to warm to room

temperature overnight. It was then cooled to 0 °C, and LiAlH4 (2.073 g, 54.54 mmol) was carefully

added with vigorous stirring (evolving gas). After 30 min, freshly degassed aqueous NaOH (2 N, 10

mL) was added. After 1 h, the organic phase was filtered through a plug of silica gel topped with a

plug of Celite®. The plugs were rinsed with THF (50 mL). The solvent was removed from the


filtrates by oil pump vacuum. The residue was distilled (Kugelrohr, 6.4 × 10–3 mbar, 196-200 °C)

to give 29d as a viscous colorless liquid (3.874 g, 16.42 mmol, 35%).

1H NMR (400 MHz, CDCl3, δ in ppm): aryl-H at 8.06 (d, J = 9.0 Hz, 1H), 7.85-7.78 (m,

3H), 7.57-7.50 (m, 5H), 7.37-7.33 (m, 3H); 5.43 (br s, PH, 1H); 13C{1H} NMR (101 MHz, CDCl3,

δ in ppm):93 134.6, 134.5, 134.2, 134.0, 133.9, 133.8, 133.2, 133.2, 133.0, 132.0, 131.9, 130.6,

130.5, 128.5, 128.5, 128.4, 128.0, 127.9, 127.7, 127.6, 126.5, 126.3; 31P{1H} NMR (162 MHz,

CDCl3, δ in ppm): –39.6 (s).

4

Recycling of Fluorous Phosphines from Organocatalytic Reactions

4.1 Introduction

4.1.1 Introduction of Fluorous Concepts and Recycling

The "art" of fluorous syntheses and the attendant applications are quite new developments

within the chemistry community. The story began in 1994 when Horváth and Rábai introduced the

adjective fluorous within a seminal publication in Science.96 In the same edition a perspective was

given by Gladysz concerning the future of fluorous catalysis.97 Many applications were

subsequently developed98 so that it is today an accepted subarea of organic chemistry. Over the

intervening years, the following general definition of fluorous has evolved:98,99 "of, relating to, or

having the characteristics of highly fluorinated saturated organic materials, molecules or molecular

fragments." In other words, compounds with aliphatic moieties that are fully or to a high degree

fluorinated are fluorous.

The most important property of fluorous solvents is the contrasting solubility or miscibility

behavior, compared to their non-fluorinated organic counterparts. All chemists know the fact that

water is immiscible with many organic solvents. Within many workup procedures this effect is

exploited to separate the product from side products. Accordingly, the organic phase is extracted

with a water solution and a simple liquid/liquid phase separation provides a preliminary purified

compound. These two liquid phases are so called orthogonal phases.

Also fluorous phases are orthogonal to many other solvents. This includes the immiscibility

with a water phase as well as with nearly all organic solvent phases. The orthogonality of aqueous,

organic, and fluorous solvents is illustrated schematically in Figure 4.1.

118 4 Recycling of Phosphine Catalysts by Fluorous Concepts

Figure 4.1. Common orthogonal liquid phases.

It is shown above that in principle, fluorous solvents are hydrophobic and lipophobic.

However, there are organic solvents that are miscible with fluorous solvents - depending on the

temperature. In other words, the orthogonal phases are immiscible at room temperature and after

heating the phase boundary disappears and the phases become miscible. Such behavior is known as

thermomorphic. This attribute was exploited by Horváth and Rábai to effect homogenous catalysis

followed by liquid/liquid biphase workup in their original publication. The schematic strategies for

catalyst recycling that were applied are illustrated on the following pages. The first method, termed

Concept A, is shown in Figure 4.2.

fluorous

organic aqueous

fluorophobic

hydr

opho

biclipophobic

4 Recycling of Phosphine Catalysts by Fluorous Concepts 119

Figure 4.2. Concept A: Recycling of a fluorous catalyst from biphasic liquid/liquid systems. I:

lower temperature, biphasic system, catalyst dissolved in phase B, substrate dissolved in phase A. II:

higher temperature, monophasic system, catalyst and substrate dissolved in the mixed phase AB. III:

lower temperature, biphasic system, catalyst dissolved in phase B, product dissolved in phase A.

As organic substrates are usually highly soluble in organic solvents (phase A), the catalyst

should be highly soluble in the orthogonal phase; in this case the fluorous one (phase B). Therefore,

a fluorous catalyst is employed. When the reaction mixture is heated the two liquid phases give one

homogenous phase (phase AB) and the catalyst is mixed with the substrates. After a reaction is

completed, the mixture is cooled and the orthogonal solvents segregate from each other. The

fluorous and organic phases can easily be separated. Ideally, the fluorous catalyst should be found

exclusively in the fluorous phase, while the organic reaction products should be found in the

organic phase. The fluorous catalyst can easily be recycled; a fresh charge of phase A and reactants

are simply added.

The question as to how a catalyst becomes fluorous is more or less answered above. There

heatingphase A

phase B

phase ABphase A

phase B

from phase A:

product separation

+

workup

I II III

: fluorous catalyst

: organic substrate

: organic product

cooling

phase A: organic solvent

phase B: fluorous solvent

recycle catalyst dissolved in phase B

Catalyst Recycling: Concept A


only has to be sufficient fluorous moieties remote from the catalytically active center. In general,

the more fluorous moieties a molecule contains, the higher the partition coefficient (relative

solubilities) between two orthogonal phases. At the same time, the longer the fluorous moieties, the

lower the absolute solubilities in all solvents.

To integrate fluorous moieties, perfluoralkyl chains are usually introduced. This method is

known as the "ponytail" concept and was also introduced in the 1994 paper.96 In practice these

ponytails usually have the formula (CH2)m(CF2)n-1CF3, which is often abbreviated as (CH2)mRfn.

The methylene chain (CH2)m can be viewed as a spacer or insulator between the

catalytically active part of the molecule and the perfluoralkyl chain Rfn. This is necessary as the

fluorine atoms are very electron withdrawing. As for all catalytic reactions, the electron density at

the active center plays a very important role; usually the electron withdrawing effect has to be

modulated by such methylene spacers. If this is achieved, the active center is decoupled from the

electron withdrawing effect, and there is furthermore the possibility to modulate the solubility of the

catalyst in organic phases. Of course, it makes no sense to synthesize a catalyst that is so fluorous,

that it is insoluble, even in the mixed phase AB. The more methylene groups are in the molecule,

the better the solubility in organic solvents.

When there is a perfect balance between the methylene spacer and Rfn moiety, the fluorous

solvent can be omitted.100,101 This second variant, Concept B, is depicted in Figure 4.3. Under

optimal conditions the catalyst remains undissolved when the substrate solution is added (I). After

heating the mixture the catalyst dissolves and the reaction takes place (II). After full conversion, it

is cooled again and the catalyst precipitates from the product solution (III). The solid catalyst and

the product solution are now separated and the catalyst is added to fresh substrate solution for the

next cycle.


Figure 4.3. Concept B: Recycling of a fluorous catalyst from biphasic solid/liquid systems. I: lower

temperature, biphasic system, undissolved solid catalyst, substrate dissolved in phase A. II: higher

temperature, monophasic system, catalyst and substrate dissolved in phase A. III: lower

temperature, biphasic system, solid undissolved catalyst, product dissolved in phase A.

Comparing Concept B with Concept A, there is the advantage that a fluorous solvent is no

longer needed. This saves money as well as natural resources, which is even more important.

However, in practice it often happens that the catalyst does not fully precipitate while cooling. To

improve this precipitation behavior, a fluoropolymer can be added as a solid support.

Fluorous compounds are fluorophilic and this also applies to fluorous solid supports.100-102

This leads to the third variant, Concept C, which is depicted in Figure 4.4.

heating

from phase A:

product separation

+

workup

: fluorous catalyst

: organic substrate

: organic product

cooling

Catalyst Recycling: Concept B

phase A phase A phase A

I IIIII

recycle solid catalyst



Figure 4.4. Concept C: Recycling of a fluorous catalyst from biphasic solid/liquid systems with

fluoropolymer support. I: lower temperature, biphasic system, undissolved solid catalyst which is

coated on a fluoropolymer, substrate dissolved in phase A. II: higher temperature, monophasic

system, catalyst and substrate dissolved in phase A, uncoated solid fluoropolymer. III: lower

temperature, biphasic system, undissolved solid catalyst which is again coated on the fluoropolymer,

product dissolved in phase A.

Here the catalyst is coated onto a fluoropolymer which could be Teflon® tape, as it is

available in every building center. Of course, every other perfluoralkane based polymer can be

employed, for example later also a Gore-Rastex® fiber was tested. The coated polymer is then

heated with the substrate mixture and the catalyst becomes soluble and diffuses into solution to

catalyze the reaction. When the reaction is complete and the mixture is cooled, the catalyst

precipitates or adsorbs onto the fluoropolymer, as both (catalyst and polymer) are fluorophilic. The

polymer can then be removed manually from the mixture and here is the second advantage of the

fluoropolymer support. With Concept B it can be challenging to remove the catalyst manually in

heating

phase A phase A phase A

I II III

cooling

recycle with catalyst coated polymer

Catalyst Recycling: Concept C

fluoropolymer

from phase A:

product separation

+

workup

: fluorous catalyst

: organic substrate

: organic product



solid form from the reaction vessel, as it precipitates over the wall of the entire vessel and the

stirring bar (which is usually a magnet coated with Teflon® polymer). Within Concept C the

catalyst can be removed from the vessel very easily by taking out the coated polymer.

4.1.2 Introduction of Fluorous Phosphines

In the years since the initial paper from Horváth and Rábai,96 a variety of processes have

been developed that exploit fluorous concepts and many of them are summarized in the "Handbook

of Fluorous Chemistry".98 Within this handbook, numerous reactions are mentioned that involve a

catalytically active metal center that is coordinated by fluorous phosphines. These fluorous

phosphines render the whole catalyst fluorophilic.

However, there are many reactions that are catalyzed by phosphines themselves without

involving an active metal center. The transformations are now termed organocatalytic reactions.8,10

In most cases the organocatalysts are not recovered, as most of this research is still in an early,

fundamental stage. But nevertheless, with a look to the future, if any reaction should become

industrially important, it would be of great advantage if the catalyst would be recoverable and

recyclable.

Therefore, the fluorous concept was applied and two aliphatic phosphines, tagged with

different chain length ponytails, were utilized for the types of intramolecular Morita Baylis Hillman

reactions described in Chapter 2. The employed phosphines are depicted in Figure 4.5.

These phosphines can be viewed in the context of three components, all necessary for

applying fluorous catalysis concepts. Of course, there must be a catalytically active center, which is

segment A. Segment B acts as a spacer that modulates the electron density at the phosphorus atom.

Especially for organocatalysis, the electron density at this atom plays a very important role as

usually the phosphine acts as a nucleophile in the initial reaction step (Schemes 1.5 and 1.8). If the

electron density is decreased by the electron withdrawing effect of the fluorine atoms, the

nucleophilicity is decreased. And by this, attenuated or dramatically lower reactivity can be

expected. Furthermore, the methylene spacers provide higher solubilities in organic solvents.

Finally, the most important part for catalyst recovery is segment C, as this is the fluorophilic part,


acting as described above.

Figure 4.5. General structure for the phosphines P((CH2)3Rfn)3 (30, a: n = 6, b: n = 8) that were

employed for the intramolecular Morita Baylis Hillman and related reactions. Segment A:

catalytically active center. Segment B: methylene spacers for modulation of electronic and

solubility properties. Segment C: fluorous tag, also for modulation of solubility properties.

The preparation of these phosphines was done according to literature procedures. All

phosphines are well known and have been previously characterized in detail.103-106 In general there

are mainly two ways to synthesize fluorous phosphines 30, as depicted in Scheme 4.1. The first is

the three-fold addition of alkenes like 31 to PH3 by a radical mechanism.103 As PH3 is a very toxic

and pyrophoric gas,107 there is much interest to avoid its use. Therefore, PH3 can be substituted by

the primary phosphines 32, which can be obtained by a two step Arbuzov sequence.104 As 32 is

also the first non-radical intermediate during the procedure with PH3, the same conditions but with

a different stoichiometry can be employed. The tertiary fluorous phosphines are obtained as a liquid

(30a) or as a solid (30b), and their application as organocatalysts are described in the following

sections.

P

(CH2)m

(CH2)m

(CH2)m

(CF2)n-1

CF3

(CF2)n-1

CF3

(CF2)n-1

CF3

30a: m = 3, n = 6

30b: m = 3, n = 8

segment A

segment Bsegment C

P((CH2)m(CF2)n-1CF3)3


Scheme 4.1. General procedure for the syntheses of tertiary fluorous phosphines 30a,b.

Rfn

Rfn

PH3

Rfn

H2P

3

P

3

31

32

330

a: n = 6

b: n = 8

initiator


4.2 Results

4.2.1 Catalytic Reactions with P((CH2)3Rf6)3 (30a)

From mechanistic considerations, it would seem that in principle every phosphine can be

employed for the Morita Baylis Hillman reaction (Scheme 1.8). While the phosphorus center is

needed for catalytic activity, the fluorous pony tail opens up many possibilities for recycling. To

apply Concepts B and C, data on catalyst solubilities are essential. Thus, preliminary tests were

conducted with the less heavily fluorinated phosphine P((CH2)3Rf6)3 (30a).106 This phosphine is a

liquid at room temperature and solidifies at ca. –45 °C upon cooling. The solubility in different

degassed solvents was qualitatively tested by "naked eye" and some results are summarized in

Table 4.1.

Table 4.1. Qualitative solubility of 0.050 g 30a in several solvents at different temperatures.

Solvent V (mL) T (°C) soluble

CH2Cl2 3.0 20 yes

CH3CN 2.3 50 yes

THF 0.3 20 yes

CH2ClCH2Cl 2.5 70 no

CDCl3 0.5 20 yes

The solubility of 30a was a strong function of solvent. At room temperature, it was highly

soluble in THF as well as in CDCl3. It was also soluble in CH2Cl2, but much more solvent volume

was needed. In the cases of CH3CN and CH2ClCH2Cl, several mL of solvent as well as elevated

temperatures were needed. In the latter, complete dissolution could not be achieved. As mentioned

before, usually very polar and/or protic solvents are used for the Morita Baylis Hillman reactions.


As CH3CN is very polar (Figure 2.15) and the fluorous phosphine 30a seemed to be insoluble at

room temperature but dissolved with heating, this phosphine was tested as a catalyst. For this, 10

mol% of 30a was employed under conditions where complete dissolution would give a 0.00500 M

CH3CN solution. The substrate C1Ph (0.0500 M) was first used, as it was known to be a smoothly

reacting one (Scheme 4.2).

Scheme 4.2. Intramolecular Morita Baylis Hillman reaction of C1Ph catalyzed by 10 mol% of

fluorous phosphine 30a.

The reaction was conducted at 60-64 °C (sand bath), which gave a homogeneous solution.

After 2.5 h, the reaction mixture was cooled to room temperature and the CH3CN phase was

carefully removed from the vial. Subsequently the solvent was replaced by CDCl3 and the mixture

was assayed by 1H NMR. The product yield was calculated from the integrals of the signals at δ =

6.68 (CH=C) and 5.30 (CHOH) ppm versus all phenyl signals. The yield was 86%, and some

unreacted C1Ph could be detected.

Under the same conditions a series of three catalytic cycles was conducted. Concept B

(Figure 4.3) was utilized and of course, the catalyst did not precipitate as a solid but as a liquid. The

yields are summarized in Table 4.2.

Details of the recycling sequence were as follows. After 2.5 h at 60-64 °C, the sample was

cooled to –30 °C for several hours to facilitate phase separation of the catalyst. The catalyst was not

detectable to the "naked eye", as it was a very small amount of a liquid that was distributed over the

whole wall of the glass vial or possibly the stirring bar. The CH3CN phase was removed by a

pipette and examined by 1H NMR as above. For the next cycle, new substrate solution was added

and the sample was heated again.

CHOPh

OO

Ph OH10 mol%

P((CH2)3Rf6)3 (30a)

C1Ph C1Phprod

CH3CN

60-64 °C


Table 4.2. Reaction of C1Ph with 10 mol% of 30a in CH3CN at 60-64 °C for 2.5 h. Product yield

as a function of cycle (Concept B).

However, the product yields decreased with every cycle and furthermore there was always

unconverted substrate. To get better results, the reaction setup was improved in two sets of

experiments. In the first, the reaction time was increased from 2.5 h to 6 h. In the second, Teflon®

shavings were furthermore added (Concept C, Figure 4.4). The results for each are given in Table

4.3.

Table 4.3. Reaction of C1Ph with 10 mol% of 30a in CH3CN at 60-64 °C for 6 h. Product yield as

a function of cycle. Catalyst was recovered by precipitation (Concept B) or adsorption onto Teflon®

shavings (Concept C).

Product Yield (%)

Cycle Concept B Concept C

1 96 92

2 78 80

3 74 20

It is easily seen that the yield of product increased with longer reaction times (96% for

Concept B vs. 86% in Table 4.2). Unfortunately, the next two cycles showed a yield decrease. Also

Cycle Product Yield (%)

1 86

2 78

3 73


the addition of Teflon® shavings gave no improvements. Furthermore, there was a big drop in

reactivity after the second cycle. Given these recycling problems, a different phosphine catalyst was

sought.

4.2.2 Catalytic Reactions with P((CH2)3Rf8)3 (30b)

The longer the fluorous chains, the less soluble are the above mentioned phosphines. As it

seemed likely that the phosphine 30a with Rf6 moieties was partially removed with the product

solution during the recycling procedures, homologs with longer fluorous chains were targeted. The

most logical candidate was P((CH2)3Rf8)3 (30b), which in comparison to 30a is not a liquid but a

white solid at room temperature. The solubility of 30b in CH3CN was tested by the "naked eye". It

seemed that it was not soluble at room temperature, while sufficient solid disappeared at elevated

temperatures (> 50 °C) to give 0.00500 M solutions. After cooling to –30 °C for several hours, the

phosphine was found by "naked eye" as a white, solid precipitate on the glass wall.

4.2.2.1 Reactions with Substrate C1Ph

A first series was carried out with substrate C1Ph in the glove box under argon atmosphere

(Scheme 4.2, but with 30b as catalyst). A Schlenk flask was charged with 10 mol% of 30b, and a

CH3CN solution of C1Ph was added. In all cases, the final substrate concentration was 0.0500 M.

The mixture was stirred at 60-64 °C for 6 h and afterwards stored at –30 °C for several hours. The

CH3CN phase was then removed with a pipette and the yield of C1Phprod was determined by 1H

NMR as described in section 4.2.1. The vial was recharged with substrate solution and the next

cycle was run. The yields are summarized in Table 4.4.

From these data, it is clear that 30b is recovered much more efficiently than 30a. Even with

the fifth cycle a yield comparable to the first cycle was obtained.


Table 4.4. Reaction of C1Ph with 10 mol% of 30b in CH3CN at 60-64 °C for ca. 6 h. Yield as a

function of cycle (Concept B).

Cycle Yield (%)

1 70

2 76

3 69

4 73

5 68

As a next step, the reaction of substrate C1Ph with 10 mol% of catalyst 30b was monitored

with time. To confirm the accuracy, two different methods were employed. In the first, aliquots

were assayed by 1H NMR. The yields were calculated as described in section 4.2.1. In the second,

aliquots of a smaller scale independent run were assayed by HPLC. The HPLC injections were of

constant volume, and the detector adsorption of the final data point was normalized to the yield

determined by 1H NMR. In any case, the results are presented in Figure 4.6.

The green trace (■) gives the reaction profile obtained by NMR. The red one (▲) shows the

data from HPLC measurements. Both reactions ended with a yield of 85% after 24 h.


Figure 4.6. Reactions of C1Ph with 10 mol% of 30b in CH3CN at 60-64 °C. Aliquots of one were

assayed by 1H NMR (■), and the other (smaller scale) by HPLC (▲).

4.2.2.2 Reactions with Substrates C1S(i-Pr) and C1S(i-Pr)2

The catalyst 30b was tested with two more substrates. The reactions are shown in Scheme

4.3. The first leads to a Morita Baylis Hillman cyclization and the second to a Rauhut Currier

cyclization.

Reactions were monitored by 1H NMR (■) and GC (▲). The latter were conducted

independently, on smaller scales, and in the presence of an internal standard. As can be seen in

Figures 4.7 and 4.8, the larger scale reactions (conducted in Schlenk flasks) were somewhat slower.

NMR yields were calculated from the integration of the total i-Pr methine 1H NMR signal versus

characteristic products peaks. The final NMR and GC yields were in good agreement (Yields:

NMR/GC; C1S(i-Pr)prod, 95/92%; C1S(i-Pr)2prod, 75/72%).

0 5 10 15 200

20

40

60

80

( ) NMR

( ) HPLC

Yie

ld (%

)

Time (h)


Scheme 4.3. Cyclizations of substrates C1S(i-Pr) and C1S(i-Pr)2 catalyzed by 10 mol% of 30b.

Figure 4.7. Reactions of C1S(i-Pr) with 10 mol% of 30b in CH3CN at 60-64 °C. Aliquots of one


0 10 20 30 400

20

40

60

80

( ) NMR

( ) GCPro

duct

Yie

ld (%

)

Time (h)

CHOi-PrS

OO

i-PrSOH10 mol%

P((CH2)3Rf8)3 (30b)

C1S(i-Pr)prod

CH3CN

60-64 °C

C1S(i-Pr)

S(i-Pr)

O

i-PrS

O

O

i-PrS O

S(i-Pr)

C1S(i-Pr)2prodC1S(i-Pr)2

10 mol% 30b

CH3CN

60-64 °C


Figure 4.8. Reactions of C1S(i-Pr)2 with 10 mol% of 30b in CH3CN at 60-64 °C. Aliquots of one


4.2.2.3 Reactions with Substrate C2(p-Tol)

To extend the series of substrates, C2(p-Tol) was tested next. Cyclization was catalyzed as

depicted in Scheme 4.4. Due to the slower rate, a slightly higher temperature was employed. This

afforded complete reaction after 72 h.

Scheme 4.4. Cyclization of substrate C2(p-Tol) catalyzed by 10 mol% of 30b.

0 10 20 30 400

20

40

60

80

( ) NMR

( ) GCPro

duct

Yie

ld (%

)

Time (h)

p-Tol

O

C2(p-Tol)prodC2(p-Tol)

CHO

p-Tol

O

OH

10 mol% 30b

CH3CN

70-72 °C


In this case the reaction was exclusively monitored by HPLC. Since no internal standard

was present, the maximum yield (79%) was calculated from the total aryl 1H NMR signals versus

characteristic product signals. Unassigned side products were also apparent. The results are shown

in Figure 4.9.


assayed by HPLC.

The reaction was again carried out in a small vial in the glove box under the same conditions

as above. The reaction time (72 h) was somewhat longer than those of C1Ph (24 h), C1S(i-Pr), and

C1S(i-Pr)2 (48 h each) at lower temperatures (60-64 °C).

4.2.2.4 Preparative Experiments

Substrates C1S(i-Pr) and C2(p-Tol) were subjected to catalytic reactions on preparative

scales (0.120 and 0.150 g). The same reaction conditions and times as above were employed. The

crude products were purified by column chromatography. The yield of C1S(i-Pr)prod was lower

0 10 20 30 40 50 60 700

20

40

60

80

( ) HPLCPro

duct

Yie

ld (%

)

Time (h)


than the NMR yield (81% vs. 95%). However, it was already shown in Chapter 2 that always some

product is lost by silica gel chromatography. The yield of C2(p-Tol)prod was also lower (67% vs.

79%).

4.2.3 Recycling of 30b by Precipitation

As noted above, a fluorous catalyst can be recycled by cooling the mixture to lower

temperatures after the reaction is finished. The general procedure was depicted in Figure 4.3, and

termed Concept B.

Every experiment began as a biphasic mixture of 30b, the substrate, and the CH3CN solvent.

At room temperature the substrate was dissolved, but the catalyst was apparently not (I, Figure 4.3).

After heating with stirring, the catalyst dissolved and the reaction took place (II, Figure 4.3). From

this hot mixture aliquots (0.010 mL) were periodically taken by a syringe. These aliquots were

assayed by HPLC or GC. These data were used for the reaction profiles. After the reaction was

finished, the mixture was cooled and the catalyst precipitated (III, Figure 4.3). Recycling was

facilitated when the samples were cooled slowly (3 h at room temperature followed by –30 °C

overnight). The resulting precipitate was coarser. The product solution was carefully removed by

syringe and assayed by 1H NMR. The remaining solid catalyst was washed with a small amount of

CH3CN at room temperature and dried by oil pump vacuum. The vial with the recycled catalyst was

then recharged with a CH3CN solution of substrate. With each cycle less substrate solution was

added to compensate for the catalyst removed in aliquots (i.e., to maintain the 10 mol% catalyst

loading). The next cycle was conducted similarly with respect to monitoring and recycling. After

the last cycle, the recovered catalyst was dissolved in PhCF3, and 1H NMR and 31P{1H} NMR

spectra were recorded to give information about the resting state.

4.2.3.1 Recycling from Reactions with C1Ph

The first set of recycling reactions was carried out with substrate C1Ph and 10 mol% of 30b

in CH3CN. The same procedure as given in Figure 4.3 was applied at a reaction temperature of 60-


64 °C. All reactions were carried out in the glove box under an argon atmosphere in a sand bath.

Photographs of a representative sequence are given in Figure 4.10.

A B C D

Figure 4.10. A: Reaction mixture prior to heating. B: Reaction mixture after cooling. C: Catalyst

after separation from the reaction mixture. D: Recovered catalyst.

The vial with the starting mixture (A) shows a clear solution with a solid residue at the

bottom that is difficult to see. The phosphine 30b is a white solid but becomes somewhat

transparent upon the addition of CH3CN. After the reaction finished a red solution was obtained (B).

As described in section 2.5.4, the product C1Phprod should be a slightly yellow oil. The color was

attributed to unassigned side products. In particular, dehydration involving the secondary alcohol

would give a conjugated cyclic diene that could be prone to further condensations. After removing

the product solution, the catalyst was obtained as a slightly transparent solid (C). This solid was

washed and dried under oil pump vacuum and a white solid was again obtained (D). This was

employed for the next reaction cycle. The results of five cycles are charted in Figure 4.11.

There was nearly no loss in reactivity within the first three cycles. The yields after the

reactions ended were comparable (85%, 83%, and 84%). Also the reaction rates were similar.

Unfortunately, with the fourth and fifth cycle the reactivity decreased a little and lower yields (both

78%) were obtained.


Figure 4.11. Reaction of C1Ph with 10 mol% of 30b in CH3CN at 60-64 °C. Aliquots were

assayed by HPLC.

Formation of phosphine oxide. After the fifth cycle the recovered catalyst was assayed by

1H NMR and 31P{1H} NMR. The spectra showed that 24% of the phosphine was oxidized (ca. 2%

in a parallel experiment after one cycle). The phosphine oxide O=P((CH2)3Rf8)3 (O=30b) has been

reported in the literature106 and was for comparison purposes synthesized by the oxidation of 30b

with H2O2.103

4.2.3.2 Recycling from Reactions with C1S(i-Pr), C1S(i-Pr)2, and C2(p-Tol)

Following the procedures shown above for C1Ph, three other substrates were similarly

studied, with catalyst recycling by precipitation at low temperatures (Concept B). For substrate

C2(p-Tol), higher reaction temperatures were employed (60-64 °C vs. 70-72 °C), as the formation

of six-membered ring systems is slower than five-membered analogs. The data are presented in

Figures 4.12-4.14.

0 5 10 15 200

20

40

60

80

( ) Cycle 1 ( ) Cycle 2 ( ) Cycle 3 ( ) Cycle 4 ( ) Cycle 5P

rodu

ct Y

ield

(%)

Time (h)


Figure 4.12. Reaction of C1S(i-Pr) with 10 mol% of 30b in CH3CN at 60-64 °C. Aliquots were

assayed by GC.

Figure 4.13. Reaction of C1S(i-Pr)2 with 10 mol% of 30b in CH3CN at 60-64 °C. Aliquots were

assayed by GC.

0 10 20 30 400

20

40

60

80

( ) Cycle 1 ( ) Cycle 2 ( ) Cycle 3P

rodu

ct Y

ield

(%)

Time (h)

0 10 20 30 400

20

40

60

80


rodu

ct Y

ield

(%)

Time (h)



assayed by HPLC.

In each case very good results were obtained. The three cycles in Figure 4.12 gave yields of

95% to 96%, which can be considered within experimental error. However, the product mixtures

were yellow, indicating the formation of unassigned side products. Indeed, yellow to orange

product mixtures were obtained for all substrates.

The third cycle with the substrate C1S(i-Pr)2 (Figure 4.13) appeared to show a little loss of

activity. However, the yield after 48 h was comparable to that in the first cycle (with 73% vs. 72%).

The first two cycles with C2Tol (Figure 4.14) are virtually identical. There is some scatter in

the third cycle, suggestive of artifactual data points. The NMR yields ranged from 79% to 81%.

Formation of phosphine oxide. As in the section before, the recovered catalysts were

examined by 1H NMR and 31P{1H} NMR. In every experiment phosphine oxide O=30b was found,

indicating the presence of oxygen or other oxidation mechanisms that were not investigated. The

data are summarized in Table 4.5.

0 10 20 30 40 50 60 700

20

40

60

80


rodu

ct Y

ield

(%)

Time (h)


Table 4.5. Phosphine oxide O=30b formed during the reactions in Figures 4.12-4.14, as assayed by

1H NMR and 31P{1H} NMR spectra. The result after the first cycle is from an independent reaction.

4.2.4 Recycling of 30b with Fluoropolymer Supports

As shown above, catalyst precipitation can be a very useful recycling method. However, it

can be problematic when the catalyst precipitates on the walls of the reaction vessel, especially if it

has to be transferred to another vessel, and if small quantities are involved. Fortunately, these

phosphines are very fluorophilic and can easily be adsorbed to fluoropolymers from solutions by

cooling from an appropriate solvent (Concept C, Figure 4.4). This method was applied to recover

catalyst from reactions with C1Ph.

In contrast to Concept C as it is depicted above, the first cycle did not involve 30b coated

onto the fluoropolymer; rather they were added separately. Subsequently, C1Ph and the solvent

were added to the vial at room temperature in a glove box. The mixture was then treated under

conditions identical to the reactions without fluoropolymer support. This meant heating to 60-64 °C

with stirring and regularly taking aliquots that were assayed by HPLC. After the reaction time (24

h), the vial was kept at room temperature for 3 h and then at –30 °C overnight. Then the product

solution was removed and the fluoropolymer, now coated with the catalyst, was washed. After

drying the coated polymer by oil pump vacuum, it was transferred to another vial that had been

precharged with substrate solution, and the next cycle begun.

Reaction with substrate

C1S(i-Pr) C1S(i-Pr)2 C2(p-Tol)

After cycle 1 4 / 96 2 / 98 7 / 93 O=30b / 30b

After cycle 3 23 / 77 12 / 88 12 / 88


4.2.4.1 Recycling with the Support of Teflon® Tape

The first experiments employed commercial Teflon® tape, as it is available in every

building center for sealing water pipe connections. It is a very thin material and therefore offers a

large surface for potential adsorption per unit weight. The mixture was treated under the same

conditions as shown above (Figure 4.6). Some photographs from different stages are depicted in

Figure 4.15.

A B C


Reaction mixture after cooling to –30 °C. C: Washed and dried Teflon® tape, coated with catalyst.

The Teflon® tape is apparent as the white solid in picture A. Again the catalyst can hardly

be seen as it is quite transparent. Picture B shows the mixture, from which the tape was removed

after the completion of the reaction and cooling. Again a red coloring occurred that was similar to

that without fluoropolymer support. After the Teflon® tape was removed from the reaction mixture

it was washed with CH3CN. Neither in the reaction mixture nor in the washing solvent could solid

catalyst be seen by the "naked eye". This suggests that the tape is firmly coated with the catalyst.

This tape shown in picture C was directly employed for the next cycle. During each cycle, aliquots

were assayed by HPLC, and the results are shown in Figure 4.16.



Teflon® tape. Aliquots were assayed by HPLC.

As depicted, five cycles were conducted, showing a gradual loss in activity of the catalyst.

The fifth cycle resulted in a yield of 66%, as opposed to the 82% reached in the first one. There was

substrate left in the fifth cycle, and also some side product. With the first cycle, the substrate C1Ph

was fully consumed. However, the first cycle also started quite slowly, as illustrated by the green

trace. This was assumed to be due to poor convection in the vial when the experiment was started.

The catalyst was a solid at the bottom of the vial and the tape, which is quite voluminous, was

stacked above (A, Figure 4.15). After warming the mixture, the catalyst dissolved but the tape

hindered the generation of a homogenous catalyst solution. Additionally, though two stirring bars

were employed, stirring was very ineffective as the stirring bars were hindered from moving by the

Teflon® tape. In subsequent cycles the catalyst dissolved directly from the coated tape and therefore

gave a homogenous solution right from the start. Accordingly, these run faster at the beginning.

0 5 10 15 200

20

40

60

80

( ) Cycle 1 ( ) Cycle 2 ( ) Cycle 3 ( ) Cycle 4 ( ) Cycle 5

Pro

duct

Yie

ld (%

)

Time (h)


4.2.4.2 Recycling with the Support of Gore-Rastex® Fiber

Another attractive option for the fluoropolymer support would be Gore-Rastex® fiber. This

material can be viewed as Teflon® that is converted by special techniques to give a fiber that is very

porous. This affords a material with many small holes that are permeable for small molecules, such

as a water. But it is impermeable to large aggregates of molecules, such as water drops. The fiber on

one side and the porous material on the other offer a very large surface for the adsorption of

fluorous catalysts such as 30b. It was assumed that this could improve the capacity for recovery by

the fluoropolymer support, according to Concept C.

All conditions were analogous to the experiment with Teflon® tape in section 4.2.4.1.

Pictures were taken directly from the experiment from time to time and are depicted in Figure 4.17.

The observations were similar to those in the experiments with the Teflon® tape and are therefore

not repeated. The results of monitoring the reaction of C1Ph with 10 mol% of catalyst are shown in

Figure 4.18.

This figure shows that good recovery of the catalyst was obtained with Gore-Rastex® fiber

support. There is a definite improvement over the results with Teflon® tape. The biggest loss in

catalyst activity was found after the fourth cycle. The catalyst recovery in the cycles before was

quite reliable. Anyway, within any cycle good yields were obtained (82%, 80%, 81%, 78%, and

74%; cycle 1-5).

At low conversion, the first cycle appeared "normal", without the quasi induction period

behavior in Figure 4.16. It was assumed that the fiber allows near-normal fluid convection in the

sample.


A B C


Reaction mixture after cooling. C: Washed and dried Gore-Rastex® fiber, coated with catalyst.


Gore-Rastex® fiber. Aliquots were assayed by HPLC.

Formation and reactivity of phosphine oxide. As in the above sections, phosphine oxide

was also found after the reaction was finished. This was despite the fact that the reactions were

performed in the glove box. The amounts detected by 1H NMR and 31P{1H} NMR are summarized

in Table 4.6.

0 5 10 15 200

20

40

60

80

( ) Cycle 1 ( ) Cycle 2 ( ) Cycle 3 ( ) Cycle 4 ( ) Cycle 5

Pro

duct

Yie

ld (%

)

Time (h)


Table 4.6. Phosphine oxide O=30b formed during the reactions in Figures 4.11, 4.16, and 4.18 as

assayed by 1H NMR and 31P{1H} NMR spectra.

Recovery method

Precipitation Teflon® tape Gore-Rastex® fiber

O=30b / 30b 24 / 76 25 / 75 37 / 63

To exclude that phosphine oxide O=30b shows reactivity towards substrate C1Ph, a control

experiment was conducted. Therefore, a reaction mixture with substrate C1Ph analogous to the

precipitation experiments (section 4.2.3.1) was prepared, but with O=30b instead of 30b. This

mixture was heated to 60-64 °C with stirring. The oxide appeared to be insoluble in CH3CN under

such conditions. After 24 h, the mixture was allowed to cool and assayed by 1H NMR. No

detectable amount of C1Phprod was present. However, very low amounts of decomposition

products of C1Ph were noted.

Horváth also reported that this phosphine oxide was very poorly soluble.106 In fact, while

conducting the recycling experiments in section 4.2.3, after several cycles small amounts of

precipitates were noted in the warm reaction mixtures. These precipitates were never isolated but

are thought to be O=30b.

4.2.5 Thermomorphic Behavior of 30b in CH3CN

The "naked eye" determinations mentioned above indicated that 30b seems to be insoluble

in CH3CN at room temperature, but to have appreciable solubility at elevated temperature. As a

check, the solubility of 30b in CH3CN was assayed by 19F NMR at different temperatures, using

Na+ BArf– (0.00188 M) as an internal standard.108 The relative areas of the CF3 signals were

integrated. The influence upon the solubility of 30b was presumed to be minimal.

The results are shown in Figure 4.19. Hysteresis was evident. The heating curve (red trace,


■), which was extended to just under the boiling point of CH3CN (82 °C) showed the expected

marked solubility increase. The probe was equilibrated for 5 min at every temperature, and the 384

pulses were collected. Although no 30b was detected at 25 °C and 35 °C, the signals could have

been obscured by the noise. Some very low solubility is likely.

The cooling curve (blue trace, ▲) gave higher solubilities. However, it is likely that the

hysteresis could decrease, if the samples had been equilibrated 1 h at each temperature instead of 5

min. Nonetheless, the maximum concentration of 30b attained in Figure 4.19 is only 0.00321 M, as

opposed to the 0.00500 M solutions used for the catalysis experiments that were by the "naked eye"

homogeneous. However, there is a possible rationale. With all of these observations, an excess of

the substrate C1Ph (0.0500 M) was present. During the first step of the catalysis mechanism

(Schemes 1.5 and 1.8), a zwitterion is generated. Although the equilibrium constant is unknown, to

the extent that catalyst-substrate or catalyst-product adducts are present, increased solubilities can

be anticipated.

Figure 4.19. Solubility of 30b in CH3CN as a function of temperature. The hysteresis curve was

determined from two independent 19F NMR experiments. Red trace (■): heating curve. Blue trace

(▲): cooling curve.

20 40 50 60 70 80 0.0

0.5

1.0

1.5

2.0

2.5

3.0

Pho

sphi

ne C

once

ntra

tion

(mM

)

Temperature (°C)

30


4.3 Discussion

The above experiments demonstrate that the fluorous phosphines 30a and 30b are effective

catalysts for the Morita Baylis Hillman reaction of substrate C1Ph as well as others. Good yields of

the product C1Phprod were obtained. However, recycling of catalyst 30a was not as effective as for

catalyst 30b (Tables 4.2 and 4.3 vs. Table 4.4, Figures 4.11, 4.16, and 4.18). It is presumed that 30a

has a higher solubility at room temperature in CH3CN than 30b. Thus, the catalyst leaching during

the workup procedure was higher for 30a.

While a reaction mixture containing catalyst 30a and substrate C1Ph gave a 96% yield of

C1Phprod after 6 h (Table 4.3), an analogous mixture but with catalyst 30b gave only a 70% yield

after the same time (Table 4.4). Hence, although a detailed reaction profile for catalyst 30a is not

available, a higher reactivity in the former mixture can be supposed. As the structures of the

catalysts only vary in two CF2 groups (per alkyl chain) this observation might be attributed to

solubility effects.

Prior to this study, three catalyst systems had been shown to be recyclable using

fluoropolymer supports. The first involved the use of Teflon® shavings as a mechanical support for

recycling the fluorous phosphine P((CH2)2Rf8)3, which is an effective Lewis base or nucleophilic

catalyst for additions of alcohols to propiolate esters (n-octane, 65 °C).100,101 The second

demonstrated the use of Teflon® tape as an adsorbent for recycling a rhodium hydrosilylation

catalyst derived from ClRh[P((CH2)2Rf6)3]3 (dibutyl ether, 55 °C).102 The third and newest study

employed Teflon® tape for recycling of a fluorous phase transfer catalyst

(Rf8(CH2)2)(Rf6(CH2)2)3P+ X– (X = Cl/I) acting in a biphasic liquid/liquid system (H2O/PhCF3,

100 °C).109 This successful series of fluoropolymer supported catalyst recycling has been

significantly extended with this study. Furthermore, the enhanced recycling capabilities of Gore-

Rastex® fiber compared to Teflon® tape has been shown. However, precipitation of the catalyst in

the absence of a support remains superior. It has been demonstrated that catalysts can be identified

that are both effective for the Morita Baylis Hillman reaction - a process very sensitive to the exact


conditions - and on the other hand can be recycled very efficiently. In most studies involving Morita

Baylis Hillman reactions no catalyst recycling is reported.

However, to the author's knowledge, to date there is only one publication, wherein the

catalyst from a Morita Baylis Hillman reaction is recycled from a liquid/liquid biphase system

(Concept A). It deserves emphasis, as the catalyst was recovered with nearly no leaching. The

catalytic system, developed by Yi, is depicted in Scheme 4.5.30 It consists of two parts. One is the

ytterbium salt, which acts as an electrophilic activator for carbonyl groups. The other is a fluorous

pyridine derivative. With this system, five reaction cycles were conducted with no loss in activity.

Although this catalyst system nicely complements the one used in this study, and points the way to

even more future developments, it does suffer in the need for a fluorous solvent. Furthermore, this

system is totally different to the one used in this work.

Scheme 4.5. Reaction sequence with recyclable catalyst system, reported by Yi.

N

R

R = CH(CH2CH2Rf8)2

OCH3

O

OCH3

O

Ph

OH

PhCHO +0.5 mol%

3 mol%

Yb(OSO2Rf8)3


4.4 Experimental

4.4.1 General Data

NMR spectra were recorded on Bruker 300 MHz or 400 MHz FT spectrometers at ambient

probe temperature (27 °C, unless noted) and referenced to the residual solvent signal (1H: CHCl3,

7.26 ppm; 13C{1H}: CDCl3, 77.0 ppm). IR spectra were recorded on an ASI React IR®-1000

spectrometer. HPLC analyses were conducted with a ThermoQuest instrument package

(pump/autosampler/detector P4000/AS3000/UV6000 LP; Column: Macherey-Nagel, Nucleosil

100-5). GC analyses were conducted with a ThermoQuest TRACE GC 2000 instrument with FID

and an Optima-5-0.25 μm capillary column. The Gore-Rastex® fiber (30 den) was obtained as a

sample from Gore corporation (http://www.gore.com/en_xx/products/fabrics/sewing/ras-

tex_weave_datasheet.html).

Solvents were treated as follows: CH3CN (Grüssing), distilled from CaH2, and for catalysis

furthermore freeze-pump-thaw degassed (3 ×); PhCF3 (ABCR), freeze-pump-thaw degassed (3 ×);

n-Bu2O (Acros, 99%), freeze-pump-thaw degassed (3 ×); isopropanol (Roth) and hexanes (Fischer)

for HPLC, used without purification; CDCl3 (99.8%, Deutero GmbH), used without purification.

The phosphines P((CH2)3Rf6)3 (30a)110 and P((CH2)3Rf8)3 (30b)103 have been previously

reported. Both were obtained by a sequence involving an Arbuzov reaction, thereby avoiding PH3

(Scheme 4.1).103,104

4.4.2 Analytic Experiments Listed by Figures or Tables

4.4.2.1 Experiments with Catalyst 30a

Recycling Sequence A (Tables 4.2 and 4.3). A vial was charged with C1Ph (0.0188 g,

0.100 mmol), evacuated (10–2 mbar), filled with N2, and transferred into an argon glove box. The

vial was further charged with 30a (0.0114 g, 0.0100 mmol)110 and CH3CN (2.00 mL) to give a


0.0500 M solution of C1Ph. The mixture was heated at 60-64 °C (sand bath) with stirring. After 2.5

h (Table 4.2) or ca. 6.0 h (Table 4.3), the mixture was cooled to –30 °C (overnight). The

supernatant was carefully separated by pipette, taken to dryness, and dissolved in CDCl3. A 1H

NMR spectrum was recorded. The yield of C1Phprod was calculated by integration of the signals at

δ = 6.68 (CH=C) and 5.30 (CHOH) ppm versus all phenyl signals. The vial was recharged with a

0.0500 M CH3CN solution of C1Ph (2.00 mL) and the above procedure repeated.

Recycling Sequence B (Table 4.3). A vial was charged with C1Ph (0.0188 g, 0.100 mmol),

evacuated (10–2 mbar), filled with N2, and transferred into an argon glove box. The vial was further

charged with 30a (0.0114 g, 0.0100 mmol),110 Teflon® shavings (PFA440HPFE, ca. 0.10 g) and

CH3CN (2.00 mL) to give a 0.0500 M solution of C1Ph. The mixture was heated at 60-64 °C (sand

bath) with stirring. After 6 h, the mixture was cooled to –30 °C (overnight). The supernatant was

carefully separated from the coated Teflon® shavings by pipette, taken to dryness, and analyzed per

sequence A.

The coated Teflon® shavings were dried by oil pump vacuum and transferred to another vial

that was charged with a 0.0500 M CH3CN solution of C1Ph (2.00 mL). The above procedure was

repeated.

4.4.2.2 Experiments with Catalyst 30b

Monitoring by 1H NMR (Figures 4.6-4.8). A Schlenk flask was charged with C1Ph,

C1S(i-Pr), or C1S(i-Pr)2, evacuated (10–2 mbar), filled with N2, and transferred into an argon glove

box. The flask was further charged with 30b (10 mol%)103,104 and CH3CN (typically 5-7 mL) to

give a 0.0500 M solution of substrate. The mixture was heated at 60-64 °C (sand bath) with stirring.

Aliquots were periodically removed (0.600 mL). The solvent was replaced by CDCl3 and the

solutions analyzed by 1H NMR spectroscopy (the yields were calculated as follows: C1Phprod, see

section 4.4.2.1; C1S(i-Pr)prod, by integration of the signals at δ = 6.89 (CH=C) and 5.14 (CHOH)

ppm versus all i-Pr methine signals; C1S(i-Pr)2prod, by integration of the signal at δ = 6.80 (CH=C)

ppm versus all i-Pr methine signals). The NMR monitoring gave the following data:


Yield (%)

Time (h) C1Phprod C1S(i-Pr)prod C1S(i-Pr)2prod

0 0 0 0

1 10 3 4

2 22 7 8

3 31 11 13

5 50 22 21

7 62 30 27

9 72 40 34

12 79 50 44

24 85 76 64

48 92 75

Recycling Sequence A (Figures 4.6-4.9 and 4.11-4.14). A vial was charged with C1Ph,

C2(p-Tol), C1S(i-Pr), or C1S(i-Pr)2 (0.100 mmol), evacuated (10–2 mbar), filled with N2, and

transferred into an argon glove box. The vial was further charged with 30b (0.0141 g, 0.0100

mmol)103,104 and CH3CN (2.00 mL; C1S(i-Pr) or C1S(i-Pr)2, GC standard n-Bu2O, 0.0500 M) to

give a 0.0500 M solution of substrate. The mixture was heated at 60-64 °C (sand bath; C2(p-Tol),

70-72 °C) with stirring. Aliquots were periodically removed (0.010 mL), diluted with CH3CN

(C1Ph or C2(p-Tol), 1.50 mL; C1S(i-Pr) or C1S(i-Pr)2, 0.180 mL) and analyzed (C1Ph or C2(p-

Tol), HPLC; C1S(i-Pr) or C1S(i-Pr)2, GC). After reaction ceased (C1Ph, 24 h; C1S(i-Pr) or C1S(i-

Pr)2, 48 h; C2(p-Tol), 72 h), the mixture was cooled to room temperature (3 h) and then –30 °C

(overnight). The supernatant was carefully separated from the precipitated 30b by syringe, taken to

dryness, and dissolved in CDCl3. A 1H NMR spectrum was recorded and the product yield

calculated (C1Phprod, C1S(i-Pr)prod, or C1S(i-Pr)2prod, see above; C2(p-Tol)prod, by integration

of the signals at δ = 6.70 (CH=C) and 4.71 (CHOH) ppm versus all aryl signals).

The precipitated 30b was washed with CH3CN (0.5 mL) and dried by oil pump vacuum.

The vial was recharged with a 0.0500 M CH3CN solution of substrate (1.92 mL; C1S(i-Pr) or


C1S(i-Pr)2, GC standard n-Bu2O, 0.0500 M) and the above procedure repeated. The volume was

decreased by 0.080 mL for each cycle to compensate for the catalyst lost in the aliquots. After the

final cycle, the catalyst was washed with CH3CN (0.5 mL), dried by oil pump vacuum, and

dissolved in PhCF3. Then 1H NMR and 31P{1H} NMR spectra were recorded (data: Tables 4.5 and

4.6).

Recycling Sequence B (Figure 4.16). A vial was charged with C1Ph (0.0188 g, 0.100

mmol), evacuated (10–2 mbar), filled with N2, and transferred into an argon glove box. The vial was

further charged with 30b (0.0141 g, 0.0100 mmol), Teflon® tape (0.160 g, ca. 550 × 12 mm) and

CH3CN (2.00 mL) to give a 0.0500 M solution of C1Ph. The mixture was heated at 60-64 °C (sand

bath) with stirring. Aliquots were periodically analyzed per sequence A. After 24 h, the mixture was

cooled to room temperature (3 h) and then –30 °C (overnight). The supernatant was carefully

separated from the coated Teflon® tape by syringe, taken to dryness, and analyzed per sequence A.

The coated Teflon® tape was washed with CH3CN (4 × 1.5 mL) and dried by oil pump vacuum.

Another vial was charged with a 0.0500 M CH3CN solution of C1Ph (1.92 mL) and the coated

Teflon® tape. The above procedure was repeated. The volume was decreased by 0.080 mL for each

cycle to compensate for the catalyst lost in the aliquots. After the final cycle, the Teflon® tape was

washed with CH3CN (4 × 1.5 mL) and dried by oil pump vacuum, and the coating dissolved in

PhCF3. Then 1H NMR and 31P{1H} NMR spectra were recorded (data: Table 4.6).

Recycling Sequence C (Figure 4.18). This was conducted identically to sequence B, using

Gore-Rastex® fiber (0.160 g) in place of Teflon® tape.


HPLC monitoring of the reaction of C1Ph with 30b according to sequence A (Figures 4.6

and 4.11) gave the following data:

Yield C1Phprod (%)

Time (h) Cycle 1 Cycle 2 Cycle 3 Cycle 4 Cycle 5

0 0 0 0 0 0

1 14.7 16.3 15.2 12.8 12.9

2 31.1 30.7 32.2 26.7 25.9

3 46.8 45.2 47.1 40.3 34.4

5 62.9 60.1 65.5 57.7 53.9

7 73.6 72.9 71.1 65.9 61.0

9 80.8 79.4 79.8 73.8 71.5

12 83.9 82.1 83.5 79.2 74.1

24 84.5 83.0 83.5 78.4 78.1

HPLC monitoring of the reaction of C1Ph with 30b according to sequences B and C

(Figures 4.16 and 4.18) gave the following data:

Yield C1Phprod (%); catalyst recovery by Teflon® tape


0 0 0 0 0 0

1 5.6 14.4 9.4 7.7 6.2

2 20.3 29.3 18.6 15.9 12.3

3 36.5 39.4 25.2 23.7 16.9

5 57.6 53.1 35.6 35.5 23.9

7 68.9 64.6 46.6 45.0 33.8

9 78.6 70.0 61.4 53.1 42.5

12 79.7 75.5 69.4 57.5 52.0

24 81.6 78.4 74.9 69.8 65.5


Yield C1Phprod (%); catalyst recovery by Gore-Rastex® fiber


0 0 0 0 0 0

1 17.4 16.5 13.5 10.2 7.3

2 27.7 28.4 26.1 23.0 12.9

3 -- 39.5 39.7 34.3 18.5

5 60.7 59.2 58.4 47.6 29.1

7 71.5 68.9 68.5 59.1 39.7

9 76.7 71.9 73.3 67.4 50.8

12 84.0 73.7 79.7 77.3 60.6

24 82.0 80.0 80.5 77.7 73.7

HPLC monitoring of the reaction of C2(p-Tol) with 30b according to sequence A (Figure

4.14) gave the following data:

Yield C2(p-Tol)prod (%)

Time (h) Cycle 1 Cycle 2 Cycle 3

0 0 0 0

1 0.4 1.5 3.3

2 2.5 3.8 5.6

3 4.7 5.9 7.0

5 9.7 9.8 11.0

7 13.7 15.9 17.1

9 19.8 17.1 25.7

12 26.8 25.6 32.2

24 47.6 46.0 55.6

48 69.2 71.1 62.2

72 79.3 81.1 79.1


GC monitoring of the reactions of C1S(i-Pr) or C1S(i-Pr)2 with 30b according to sequence

A (Figures 4.12 and 4.13) gave the following data:

Yield C1S(i-Pr)prod (%) Yield C1S(i-Pr)2

prod (%) Time (h) Cycle 1 Cycle 2 Cycle 3 Cycle 1 Cycle 2 Cycle 3

0 0 0 0 0 0 0

1 2.3 3.0 3.6 -- 3.7 5.1

2 12.1 10.2 9.6 6.8 9.0 10.2

3 19.8 22.5 16.3 -- 11.9 16.8

5 -- 39.8 39.1 24.2 17.6 26.4

7 48.1 49.3 45.7 35.2 26.7 --

9 -- 59.4 51.7 -- -- 38.7

12 -- 64.5 65.2 -- 43.4 46.0

24 79.9 80.7 84.1 69.2 66.8 64.3

48 95.0 95.0 96.0 72.0 71.0 73.0

4.4.3 Preparative Reactions

Reaction of (C1S(i-Pr) or C2(p-Tol) with 30b. A flask was charged with C1S(i-Pr) (0.120

g, 0.645 mmol) or C2(p-Tol) (0.150 g, 0.694 mmol), evacuated (10–2 mbar), filled with N2, and

transferred into an argon glove box. The vial was further charged with 30b (0.0912 g, 0.0645 mmol

or 0.0982 g, 0.0694 mmol)103,104 and CH3CN (12.9 mL or 13.9 mL) to give a 0.0500 M solution of

substrate. The mixture was heated at 60-64 °C or 70-72 °C (sand bath) with stirring.

After 48 h or 72 h the mixture was cooled to –30 °C (overnight). The supernatant was

carefully separated from the precipitated 30b by syringe, taken to dryness by rotary evaporation,

and purified by column chromatography as detailed in section 2.5.4. Yields (section 4.2.2.4): C1S(i-

Pr)prod: 0.0804 g, 0.432 mmol, 81%; C2(p-Tol)prod: 0.122 g, 0.562 mmol, 67%.


4.4.4 Thermomorphic Behavior of 30b

Solubility of 30b in CH3CN as a function of temperature (Figure 4.19). A NMR tube

was charged under argon with 30b (0.00490 g, 0.00347 mmol),103,104 and a CH3CN solution of

Na+ BArf– internal standard (0.00188 M; 0.693 mL).108 The tube was transferred to a NMR probe

that was warmed in stages. After 5 min at each temperature, a 19F NMR spectrum was recorded

(384 pulses). The concentration of 30b was calculated by integration of the signals at δ = –62.8 (s,

CF3, Na+ BArf–) and –82.3 (t, 3J(F,F) = 9.8 Hz, CF3, 30b) ppm. The probe temperature was

similarly cooled in stages. Results from two independent experiments were averaged to give the

following data:

Temperature (°C) Concentration (mM)

25 0

35 0

45 0.470

50 0.730

55 0.972

60 1.28

65 1.67

70 2.17

75 2.67

80 3.20

80 3.21

70 2.59

60 1.91

50 1.33

40 0.705

30 0.311

5

Preparation of Substrates

5.1 Introduction

In order to study the intramolecular Morita Baylis Hillman reaction as described in the

previous chapters, suitable dicarbonyl substrates were necessary. Hence, efficient syntheses were

sought. The existing literature gives three routes. One is from Koo, who started with 2-

cyclohexenone (Scheme 5.1).28

Scheme 5.1. General route to substrates C1R, published by Koo.

After oxidation of 2-cyclohexenone at the position α to the carbonyl group to an acetoxy

derivative, a nucleophile RLi is added. This gives a 1,2-addition product, and simultaneously the

acyl ester is attacked by RLi and cleaved. The resulting cyclic glycol is then cleaved with Pb(OAc)4

to give the desired substrate.

Another route was found earlier by Denmark (Scheme 5.2).46 He used the fact that there is

always an equilibrium between cyclic hemiacetals and their acyclic aldehyde form.

O

Pb(OAc)4

O

OAcRLi

HOOH

R

CHOR

O

Pb(OAc)4

C1R

158 5 Preparation of Substrates

Scheme 5.2. General route to substrates C1R, published by Denmark.

The procedure starts with the commercially available 2-hydroxytetrahydrofuran and its open

form, 4-hydroxybutyraldehyde. This reacts with a stable ylide as shown. The resulting alcohol is

then oxidized by pyridinium chlorochromate (PCC) to the aldehyde, giving the desired substrate

C1R.

The third method was first published by Murphy and is shown in Scheme 5.3.20

Scheme 5.3. General route to substrates C1R, published by Murphy.

In contrast to Denmark's method, a dialdehyde is employed from the beginning. This reacts

similarly in a Wittig reaction with stable ylides as above, yielding directly the desired substrates

C1R.

This last method was selected for substrate preparation within this work. There were several

OHO CH2OHOHC

R

O

PPh3

R

O

CH2OH

R

O

CHO

PCC

C1R

CHOOHC

R

O

PPh3

R

O

CHO

C1R

5 Preparation of Substrates 159

advantages compared to the others. One was that only (E) C=C isomers were obtained. Furthermore,

no heavy metals such as lead or chromium had to be used. For obtaining Rauhut Currier substrates

only the reactant stoichiometry had to be changed. Additionally this method was the most universal

one, allowing different chain lengths and moieties R. In the following section the preparation of

Morita Baylis Hillman as well as Rauhut Currier substrates is detailed, following the route of

Murphy.


5.2 Results

5.2.1 Preparation of the Stable Ylides

Most stable ylides employed in this study are known from the literature, but syntheses are

summarized in Scheme 5.4 anyway to show the broad applicability of these preparations. The yields

shown are those that I obtained upon synthesizing these previously reported or in some cases new

compounds.

Scheme 5.4. Preparation of the stable ylides 34.

Pred, Br2

CH2BrBr

O

EtOH, or

CH3OH, or

i-PrSHCH2BrR

O

CH3R

O

Br2

30-50%

33a: > 90%

33b: > 90%

33c: > 90%

33d: 42%

33e: 54%

33f: 36%

CH2BrR

O

PPh3

Toluene

R

O

PPh3

Br

R

O

PPh3

[34a-H]+ Br−: 70%

[34b-H]+ Br−: 80%

[34c-H]+ Br−: 91%

[34d-H]+ Br−: 75%

[34e-H]+ Br−: 92%

[34f-H]+ Br−: 60%

NaOHToluene/

H2O

34a: 76%

34b: 80%

34c: 57%

34d: 85%

34e: 52%

34f: 78%

R = Ph

p-Tol

CH3

33

CH3HO

O

33

[34-H]+ Br−

a: R = EtO

b: R = CH3O

c: R = i-PrS

d: R = Ph

e: R = p-Tol

f: R = CH3

34


In all cases, the first objective was the α-bromoacetyl derivative 33. Depending on the

moiety R, two routes were available. If RCO was an ester derivative (R = CH3O, EtO, i-PrS), the

sequence began with α-bromoacetyl bromide, which was treated with an alcohol or thiol to give the

corresponding α-brominated esters 33a-c in nearly quantitative yields (> 90%). If RCO was an acyl

moiety (R = Ph, p-Tol, CH3), the sequence began with the α-bromination of the corresponding

methyl ketone to give the bromomethyl ketones 33d-f. However, the yields were only moderate

(36-54%) due to losses during recrystallizations. In any case, as these are very basic reactions, large

amounts of starting material can be employed.

The α-brominated compounds 33 were subsequently treated with PPh3. As these reactions

were performed in toluene, the resulting phosphonium salts [34-H]+ Br– started to precipitate

directly after the reactants were mixed. The yields were good to excellent (60-91%). However,

recrystallization from EtOH was necessary in most cases. Only with the salt [34c-H]+ Br– with the

i-PrS moiety were a less polar solvent (hexanes) and a lower temperature (–24 °C) required. The

salts [34-H]+ Br– were characterized by NMR spectroscopy (1H, 13C{1H}, 31P{1H}). Although the

salts [34 (a,b,d-f)-H]+ Br– have been previously reported, NMR data are presented in the

experimental section, in cases where only partial characterization was given earlier. As the salt

[34c-H]+ Br– was a new compound, IR, elemental analysis, and melting point data are also

presented.

The salts [34-H]+ Br–, which were very slightly or even insoluble in toluene, were

subsequently deprotonated with aqueous NaOH using a biphasic water/toluene mixture. The

addition of the indicator phenolphthalein showed when an excess of NaOH was present, signifying

full deprotonation. The stable ylides 34 were very soluble in toluene and were crystallized from the

dried toluene phase. They were obtained in good yields (52-85%) and characterized by NMR

spectroscopy (1H, 13C{1H}, 31P{1H}). Although the stable ylides 34a,b,d-f have been previously

reported, NMR data are presented in the experimental section, in cases where only partial

characterization was given earlier. As ylide 34c was a new compound, IR, elemental analysis, and

melting point data are also presented.


5.2.2 Wittig Reactions of the Stable Ylides with Dialdehydes

The next and last step en route to the substrates was the Wittig reaction of the stable ylides

34 with the dialdehydes as depicted in Scheme 5.5.

Scheme 5.5. Preparation of the substrates CnR and CnR2, by reaction of ylides and dialdehydes.

First, succinaldehyde (n = 1)48,111 as well as glutaraldehyde (n = 2)112 were isolated as pure

compounds, according to the literature. These aldehydes are not stable at room temperature and

polymerize, even at –24 °C. Thus, they are not commercially available in solvent free form. Their

generation from stable acetal precursors is shown in Scheme 5.5. Moderate yields were obtained

(20-40%; literature: 30-70%).48,111,112 All subsequent Wittig reactions were carried out in dry

CH2Cl2 under N2. The yields of those reactions are summarized in Tables 5.1 and 5.2. Interestingly,

all C=C linkages were obtained as a single isomer, and were assigned to trans (E) geometries as

described below.

OHCCHO

n = 1,2

RPPh3

O

1 equiv.

2 equiv.

CHOR

O

R

O

R

O

CnR

CnR2

OOCH3H3CO

OEtO

Morita Baylis Hillman substrates

Rauhut Currier substrates

H2O/H+

H2O/H+

n = 1

n = 2

n = 1,2

n = 1,2

34


Table 5.1. Yields of substrates obtained from the reactions of succinaldehyde with ylides 34

(Scheme 5.5).

Morita Baylis

Hillman substrates

Yield (%) Rauhut Currier

substrates Yield (%)

C1OMe 40 C1S(i-Pr)2 71

C1OEt 39 C1Ph2 56

C1S(i-Pr) 71 C1Tol2 82

C1Ph 59 C1Me2 40

C1Tol 34

C1Me 35

Table 5.2. Yields of substrates obtained from the reactions of glutaraldehyde with ylides 34

(Scheme 5.5).

Morita Baylis

Hillman substrates

Yield (%) Rauhut Currier

substrates Yield (%)

C2OMe 66 C2Tol2 80

C2OEt 63 C2Me2 70

C2Ph 75

C2Tol 55

C2Me 71


5.3 Discussion

All of the reactions shown in this section are quite basic ones, of the type that can be found

in most standard textbooks. The phosphonium salts [34-H]+ Br– are very stable compounds that

never showed any sign of decomposition while stored for more than two years. They can be

deprotonated under mild conditions by NaOH to give the ylides 34.

The ylides so obtained are also quite stable. The carbanion is stabilized by the phosphonium

phosphorus atom as well as by the carbonyl group. In any event, these compounds show signs of

slow decomposition over time. The formerly white solids became yellow to orange. Nonetheless,

these slightly decomposed compounds can be successfully used for the Wittig reactions.

The subsequent Wittig reactions were all carried out in dry CH2Cl2 while warming from 0

°C to room temperature. Non dried CH2Cl2 can also be used, but the yields decreased by 5% to

10%. In any case, only (E) C=C linkages were found in the products CnR and CnR2. This was

evidenced by the values of the vinylic 1H NMR coupling constants (3J(H,H), ca. 15-16 Hz). The

products were purified by column chromatography on silica gel. As the Morita Baylis Hillman

substrates CnR are not that stable and even less stable on the very polar silica gel phase,

decomposition occurred during chromatography. The stability depends, among other factors, on the

chain length of the Morita Baylis Hillman substrates. Accordingly, the substrates with n = 1 (Table

5.1) are less stable than those with n = 2 (Table 5.2), as evidenced by the uniformly lower yields in

Table 5.1 vs. Table 5.2, and as further evidenced by their shelf lives in the refrigerator. Here, the

Morita Baylis Hillman substrates were always stored in a low temperature freezer at –60 °C.

Nevertheless, after several months some decomposition was always evident.

The Rauhut Currier substrates CnR2 are much more stable. All of these are solids that can

be stored at ambient conditions without problems. Nevertheless, they decompose during column

chromatography, with the yields ranging from acceptable to good (40-82%).

The stabilities of succinaldehyde as well as the glutaraldehyde also merit note. As pure

compounds both of them are quite unstable. The succinaldehyde, which is a liquid, gives a viscous

material after several hours at ambient conditions. After one day a glassy solid is obtained,


suggesting polymerization. On the other hand, glutaraldehyde is more stable but also decomposes to

a highly viscous mixture. In any case both could be stored as pure compounds at –60 °C for several

months.

In summary, the synthetic pathways optimized for the substrates CnR and CnR2 (n = 1, 2)

in Scheme 5.5 are simple, extremely versatile, and likely extendable to a wide variety of R groups

as well as higher values of n. This methodology is based upon a route pioneered by Murphy.20 As

described in Chapter 2, most - but not all - of the substrates undergo high yield Morita Baylis

Hillman and Rauhut Currier reactions in the presence of rhenium-containing phosphine catalysts.

Furthermore diastereomeric catalysts gave appreciable enantioselectivities.


5.4 Experimental

5.4.1 General Data

NMR spectra were recorded at ambient probe temperature on Bruker 300 and 400 MHz FT

spectrometers and referenced to the residual solvent signal (1H: CHCl3, 7.26 ppm; 13C{1H}: CDCl3,

77.0 ppm) or H3PO4 (31P{1H}, external capillary, 85%, 0.0 ppm). IR spectra were recorded on an

ASI React IR®-1000 spectrometer. Elemental analyses were determined with a Carlo Erba EA1110

CHN instrument. Melting points were measured on an Electrothermal IA 9100 apparatus.

Solvents were treated as follows: CH2Cl2 (Staub), distilled from CaH2; diethyl ether,

toluene (2 × Hedinger), n-pentane (Grüssing), ethyl acetate, hexanes, CH3OH, and EtOH (4 ×

Staub), simple distilled; CDCl3 (99.8%) and DMSO-d6 (99.0%, 2 × Deutero GmbH , used as

received.

Chemicals were treated as follows: i-PrSH (97%, Fluka) and PPh3 (99%, Acros), used as

received.

TLC was carried out with ALUGRAM® SIL G/UV254 plates (Macherey-Nagel). Column

chromatography was conducted using silica gel 60M (Macherey-Nagel).

5.4.2 Ylide Preparation

Preparation of bromomethyl ketones RCOCH2Br (33); general. A flask was charged

with α-bromoacetyl bromide (10.1 g, 50.0 mmol)113 and the alcohol/thiol (50.0 mmol) was added

dropwise at 0 °C with vigorous stirring. HBr evolved. The cold bath was removed. After 1 h, the

pure products 33a-c were obtained by distillation using a short Vigreux column (a, R = EtO, 64 °C,

30 mbar;114 b, R = CH3O, 45 °C, 20 mbar;115 c, R = i-PrS, 80 °C, 15 mbar;116 all > 90% yield).

Analytical data agreed with that in the literature.


Preparation of phosphonium bromides [R(CO)CH2PPh3]+ Br– ([34-H]+ Br–); general.

This procedure was adapted from one in the literature.117

A flask was charged with PPh3 (5.76 g, 22.0 mmol) and toluene (50 mL). The α-bromo

carbonyl compound (33a-c, 33d,118 33e,118 or 33f,119 each 20.0 mmol) was dissolved in toluene

(10 mL) and added with stirring. A white solid immediately precipitated. The mixture was kept at

120 °C for 10 min and cooled to room temperature. The precipitate was isolated and washed with

toluene (50 mL) to give a nearly pure product. The white solid was recrystallized from EtOH (for

33c 1:1 v/v EtOH/hexanes was used) to give the pure phosphonium bromide [34-H]+ Br– (a, 70%;

b, 80%; c, 91%; d, 75%; e, 96%; f, 60%).

[EtO(CO)CH2PPh3]+ Br– ([34a-H]+ Br–).114 1H NMR and 13C{1H} NMR agreed with

that in the literature. 31P{1H} NMR (162 MHz, CDCl3, δ in ppm): 21.1 (s).

[CH3O(CO)CH2PPh3]+ Br– ([34b-H]+ Br–).115 1H NMR and 13C{1H} NMR agreed with

that in the literature. 31P{1H} NMR (162 MHz, CDCl3, δ in ppm): 22.0 (s).

[i-PrS(CO)CH2PPh3]+ Br– ([34c-H]+ Br–). Dec. pt. 170 °C (capillary). Elemental analysis

calcd (%) for C23H24BrOPS (458.0): C 60.13, H 5.27, S 6.98; found: C 60.11, H 5.31, S 6.84.

1H NMR (400 MHz, CDCl3, δ in ppm): 7.80 (dd, 2J(H,P) = 13.4 Hz, 3J(H,H) = 8.1 Hz, o-

C6H5, 6H), 7.71 (t, 3J(H,H) = 7.6 Hz, p-C6H5, 3H), 7.63-7.56 (m, m-C6H5, 6H), 5.64 (d, 2J(H,P) =

13.4 Hz, CH2, 2H), 3.40 (sept, 3J(H,H) = 7.0 Hz, (CH3)2CH, 1H), 1.05 (d, 3J(H,H) = 7.0 Hz,

(CH3)2CH, 6H); 13C{1H} NMR (101 MHz, CDCl3, δ in ppm):91 190.1 (d, 2J(C,P) = 6.6 Hz, CO),

134.9 (d, 4J(C,P) = 2.9 Hz, p-C6H5), 133.8 (d, 2J(C,P) = 11.0 Hz, o-C6H5), 130.0 (d, 3J(C,P) = 13.2

Hz, m-C6H5), 117.7 (d, 1J(C,P) = 88.9 Hz, i-C6H5), 40.4 (d, 1J(C,P) = 52.3 Hz, CH2), 36.4 (s,

(CH3)2CH), 22.0 (s, (CH3)2CH); 31P{1H} NMR (162 MHz, CDCl3, δ in ppm): 21.6 (s).

IR (thin film, in cm–1):71 1668 (s, νCO).

[Ph(CO)CH2PPh3]+ Br– ([34d-H]+ Br–).120 Analytical data agreed with that in the

literature.


[p-Tol(CO)CH2PPh3]+ Br– ([34e-H]+ Br–). 1H NMR (400 MHz, CDCl3, δ in ppm): 8.20

(d, 3J(H,H) = 8.2 Hz, C6H4, o to CO, 2H), 7.89 (dd, 2J(H,P) = 13.4 Hz, 3J(H,H) = 7.4 Hz, o-C6H5,

6H), 7.70 (dt, 3J(H,H) = 7.5 Hz, 5J(H,P) = 1.9 Hz, p-C6H5, 3H), 7.60 (ddd, 3J(H,H) = 7.7 and 7.5

Hz, 4J(H,P) = 3.5 Hz, m-C6H5, 6H), 7.23 (d, 3J(H,H) = 8.1 Hz, C6H4, m to CO, 2H), 6.25 (d,

2J(H,P) = 12.2 Hz, CH2, 2H), 2.33 (s, CH3, 3H); 13C{1H} NMR (101 MHz, CDCl3, δ in ppm):

191.5 (d, 2J(C,P) = 12.2 Hz, CO), 146.0 (s, C6H4, p to CO), 134.6 (d, 4J(C,P) = 3.2 Hz, p-C6H5),

134.0 (d, 2J(C,P) = 10.7 Hz, o-C6H5), 132.7 (d, 3J(C,P) = 5.7 Hz, C6H4, i to CO), 130.1 (d, 3J(C,P)

= 13.5 Hz, m-C6H5), 130.0 (d, 4J(C,P) = 1.6 Hz, C6H4, o to CO), 129.6 (s, C6H4, m to CO), 118.9

(d, 1J(C,P) = 89.3 Hz, i-C6H5), 38.3 (d, 1J(C,P) = 61.7 Hz, CH2), 21.7 (s, CH3); 31P{1H} NMR

(121 MHz, CDCl3, δ in ppm): 23.3 (s).

[CH3(CO)CH2PPh3]+ Br– ([34f-H]+ Br–). 1H NMR (400 MHz, CDCl3, δ in ppm): 7.80

(dd, 3J(H,P) = 13.0 Hz, 3J(H,H) = 7.3 Hz, o-C6H5, 6H), 7.68 (t, 3J(H,H) = 7.3 Hz, p-C6H5, 3H),

7.60-7.54 (m, m-C6H5, 6H), 6.98 (d, 2J(H,P) = 13.6 Hz, CH2, 2H), 2.50 (d, 4J(H,P) = 2.3 Hz, CH3,

3H); 13C{1H} NMR (100 MHz, CDCl3, δ in ppm): 200.7 (d, 2J(C,P) = 7.0 Hz, CO), 134.6 (d,

4J(C,P) = 2.9 Hz, p-C6H5), 133.8 (d, 2J(C,P) = 11.0 Hz, o-C6H5), 130.0 (d, 3J(C,P) = 13.1 Hz, m-

C6H5), 118.5 (d, 1J(C,P) = 88.9 Hz, i-C6H5), 40.7 (d, 1J(C,P) = 58.9 Hz, CH2), 32.7 (d, 3J(C,P) =

6.6 Hz, CH3); 31P{1H} NMR (162 MHz, CDCl3, δ in ppm): 21.0 (s).

Preparation of ylides RCOCHPPh3 (34); general. This procedure was adapted from one

in the literature.117

An Erlenmeyer flask was charged with the phosphonium bromide [34-H]+ Br– (12.0 mmol),

water (60 mL), and some phenolphthalein. Toluene (100 mL) was added with stirring, and the

mixture was cooled to 0 °C. Then aqueous NaOH (wt 10%) was added dropwise to the emulsion

until a purple color persisted. The phases were separated. The water phase was extracted with

toluene (3 × 50 mL). The toluene phases were combined and dried (MgSO4). The solvent was

removed by rotary evaporation to give 34 as a white solid. The samples were recrystallized from

very concentrated toluene solutions to give the pure ylides 34 (a, 76%; b, 80%; c, 57%; d, 85%; e,


52%; f, 78%).

EtO(CO)CHPPh3 (34a).121,122 1H NMR (400 MHz, CDCl3, δ in ppm): 7.64 (dd, 3J(H,P)

= 12.3 Hz, 3J(H,H) = 8.0 Hz, o-C6H5, 6H), 7.53 (t, 3J(H,H) = 7.2 Hz, p-C6H5, 3H), 7.47-7.40 (m,

m-C6H5, 6H), 3.96 (br s,123 CH2, 2H), 2.87 (br s, CH, 1H), 1.16 (br s,123 CH3); 13C{1H} NMR

(100 MHz, CDCl3, δ in ppm): 171.2 (br s,123 CO), 132.9 (d, 2J(C,P) = 10.3 Hz, o-C6H5), 131.8 (d,

4J(C,P) = 2.2 Hz, p-C6H5), 128.6 (d, 3J(C,P) = 12.1 Hz, m-C6H5), 127.8 (d, 1J(C,P) = 94.4 Hz, i-

C6H5), 57.7 (s, CH2), 30.0 (d, 1J(C,P) = 129.5 Hz, CH), 14.7 (s, CH3); 31P{1H} NMR (162 MHz,

CDCl3, δ in ppm): 18.3 (s).

CH3O(CO)CHPPh3 (34b).115,124 1H NMR (400 MHz, CDCl3, δ in ppm): 7.68-7.58 (m, o-

C6H5, 6H), 7.55-7.48 (m, p-C6H5, 3H), 7.47-7.38 (m, m-C6H5, 6H), 3.51 (br s,123 CH3, 3H), 2.88

(br s, CH, 1H); 13C{1H} NMR (100 MHz, CDCl3, δ in ppm): 171.7 (br s,123 CO), 132.9 (d, 2J(C,P)

= 9.9 Hz, o-C6H5), 131.8 (s, p-C6H5), 128.6 (d, 3J(C,P) = 12.1 Hz, m-C6H5), 127.8 (d, 1J(C,P) =

88.6 Hz, i-C6H5), 49.7 (s, CH3), 29.6 (d, 1J(C,P) = 128.4 Hz, CH); 31P{1H} NMR (162 MHz,


i-PrS(CO)CHPPh3 (34c). Dec. pt. 119 °C (capillary). Elemental analysis calcd (%) for

C23H23OPS (378.1): C 72.99, H 6.13, S 8.47; found: C 72.59, H 6.11, S 8.55.

1H NMR (400 MHz, CDCl3, δ in ppm): 7.61 (dd, 3J(H,P) = 12.8 Hz, 3J(H,H) = 7.5 Hz, o-

C6H5, 6H), 7.53 (t, 3J(H,H) = 7.0 Hz, p-C6H5, 3H), 7.47-7.41 (m, m-C6H5, 6H), 3.63 (d, 2J(H,P) =

23.0 Hz, CH, 1H), 3.58 (sept, 3J(H,H) = 6.7 Hz, (CH3)2CH, 1H), 1.29 (d, 3J(H,H) = 6.8 Hz,

(CH3)2CH, 6H); 13C{1H} NMR (101 MHz, CDCl3, δ in ppm): 180.8 (d, 2J(C,P) = 5.1 Hz, CO),

132.9 (d, 2J(C,P) = 10.6 Hz, o-C6H5), 132.1 (d, 4J(C,P) = 2.9 Hz, p-C6H5), 128.8 (d, 3J(C,P) = 12.4

Hz, m-C6H5), 126.7 (d, 1J(C,P) = 90.4 Hz, i-C6H5), 47.1 (d, 1J(C,P) = 109.0 Hz, CH), 33.6 (d,

4J(C,P) = 1.5 Hz, (CH3)2CH), 24.1 (s, (CH3)2CH); 31P{1H} NMR (162 MHz, DMSO-d6, δ in ppm):

14.0 (s).

IR (thin film, in cm–1):71 1568 (s, νCO).


Ph(CO)CHPPh3 (34d).121,125,126 1H NMR (400 MHz, CDCl3, δ in ppm): 8.02-7.95 (m, o-

C6H5(CO), 2H), 7.74 (dd, 3J(H,P) = 12.3 Hz, 3J(H,H) = 7.7 Hz, o-C6H5, 6H), 7.56 (t, 3J(H,H) = 7.0

Hz, p-C6H5, 3H), 7.51-7.44 (m, m-C6H5, 6H), 7.38-7.33 (m, m-, p-C6H5(CO), 3H), 4.43 (d, 2J(H,P)

= 24.6 Hz, CH, 1H); 13C{1H} NMR (100 MHz, CDCl3, δ in ppm): 185.4 (s, CO), 141.7 (d, 3J(C,P)

= 15.4 Hz, i-C6H5(CO)), 133.6 (d, 2J(C,P) = 10.3 Hz, o-C6H5), 132.5 (s, p-C6H5), 129.8, 128.2,

127.4 (3 s, o-, m-, p-C6H5(CO)), 129.3 (d, 3J(C,P) = 12.1 Hz, m-C6H5), 127.6 (d, 1J(C,P) = 89.3 Hz,

i-C6H5), 51.0 (d, 1J(C,P) = 111.0 Hz, CH); 31P{1H} NMR (162 MHz, CDCl3, δ in ppm): 17.9 (s).

p-Tol(CO)CHPPh3 (34e).125,127 1H NMR (400 MHz, CDCl3, δ in ppm): 7.90 (d, 3J(H,H)

= 8.1 Hz, C6H4, o to CO, 2H), 7.73 (dd, 3J(H,P) = 12.5 Hz, 3J(H,H) = 7.2 Hz, o-C6H5, 6H), 7.55 (t,

3J(H,H) = 7.2 Hz, p-C6H5, 3H), 7.49-7.43 (m, m-C6H5, 6H), 7.17 (d, 3J(H,H) = 8.1 Hz, C6H4, m to

CO, 2H), 4.42 (d, 2J(H,P) = 23.7 Hz, CH, 1H), 2.36 (s, CH3, 3H); 13C{1H} NMR (100 MHz,

CDCl3, δ in ppm): 184.7 (d, 2J(C,P) = 3.3 Hz, CO), 139.2 (s, C6H4, p to CO), 138.4 (d, 3J(C,P) =

15.4 Hz, C6H4 i to CO), 133.1 (d, 2J(C,P) = 10.2 Hz, o-C6H5), 131.9 (d, 4J(C,P) = 2.8 Hz, p-C6H5),

128.8 (d, 3J(C,P) = 12.2 Hz, m-C6H5), 128.3, 126.8 (2 s, C6H4, o, m to CO), 127.1 (d, 1J(C,P) =

91.1 Hz, i-C6H5), 50.0 (d, 1J(C,P) = 112.5 Hz, CH), 21.3 (s, CH3); 31P{1H} NMR (161 MHz,


CH3(CO)CHPPh3 (34f).126 1H NMR (400 MHz, CDCl3, δ in ppm): 7.65 (dd, 3J(H,P) =

12.6 Hz, 3J(H,H) = 7.0 Hz, o-C6H5, 6H), 7.53 (t, 3J(H,H) = 7.4 Hz, p-C6H5, 3H), 7.47-7.41 (m, m-

C6H5, 6H), 3.74 (br s, CH, 1H), 2.09 (s, CH3, 3H); 13C{1H} NMR (100 MHz, CDCl3, δ in ppm):

190.7 (s, CO), 133.0 (d, 2J(C,P) = 9.9 Hz, o-C6H5), 131.9 (d, 4J(C,P) = 2.6 Hz, p-C6H5), 128.7 (d,

3J(C,P) = 12.1 Hz, m-C6H5), 127.1 (d, 1J(C,P) = 88.6 Hz, i-C6H5), 51.7 (d, 1J(C,P) = 110.1 Hz,

CH), 28.3 (d, 3J(C,P) = 15.4 Hz, CH3); 31P{1H} NMR (162 MHz, CDCl3, δ in ppm): 15.5 (s).


5.4.3 Substrate Preparation

5.4.3.1 Morita Baylis Hillman Substrates

(E)-R(CO)CH=CHCH2(CH2)nCHO; general. A flask was charged with a solution of a

dialdehyde (n = 1, succinaldehyde;48,111 2, glutaraldehyde112) in CH2Cl2 (40.0 mL, 0.300 M, 12.0

mmol) and cooled to 0 °C. Then the ylide R(CO)CHPPh3 (34a-f, 5.80 mmol) dissolved in CH2Cl2

(10 mL) was added dropwise with stirring. The mixture was allowed to warm to room temperature

overnight. The solvent was removed by rotary evaporation and the residue was extracted with

diethyl ether (3 × 20 mL). The diethyl ether was removed by rotary evaporation, and the products

were purified by column chromatography (SiO2).

(E)-Ph(CO)CH=CHCH2CH2CHO (C1Ph)25 was obtained (7:3 v/v ethyl acetate/n-pentane)

as a slightly yellow liquid (0.643 g, 3.42 mmol, 59%). Analytical data agreed with that in the

literature.

(E)-CH3O(CO)CH=CHCH2CH2CHO (C1OMe)46,47 was obtained (1:4 v/v ethyl

acetate/n-pentane) as a clear liquid (0.329 g, 2.32 mmol, 40%). Analytical data agreed with that in

the literature.

(E)-EtO(CO)CH=CHCH2CH2CHO (C1OEt)25 was obtained (2:3 v/v ethyl acetate/n-

pentane) as a clear liquid (0.353 g, 2.26 mmol, 39%). Analytical data agreed with that in the

literature.

(E)-p-Tol(CO)CH=CHCH2CH2CHO (C1(p-Tol))42,43 was obtained (3:2 v/v ethyl

acetate/n-pentane) as a slightly yellow liquid (0.398 g, 1.97 mmol, 34%). Analytical data agreed

with that in the literature.


(E)-CH3(CO)CH=CHCH2CH2CHO (C1Me)28 was obtained (7:13 v/v ethyl acetate/n-


literature.

(E)-i-PrS(CO)CH=CHCH2CH2CHO (C1(S-i-Pr)) was obtained (1:4 v/v ethyl acetate/n-

pentane) as a colorless oil (0.766 g, 4.11 mmol, 71%). Elemental analysis calcd (%) for C9H14O2S

(186.1): C 58.03, H 7.58, S 17.21; found: C 57.82, H 7.78, S 16.80.

1H NMR (400 MHz, CDCl3, δ in ppm): 9.78 (s, CHO, 1H), 6.82 (dt, 3J(H,H) = 15.5 Hz and

6.8 Hz, CH=CHCH2, 1H), 6.08 (d, 3J(H,H) = 15.5 Hz, CH=CHCH2, 1H), 3.70 (sept, 3J(H,H) = 7.0

Hz, (CH3)2CH, 1H), 2.63 (t, 3J(H,H) = 7.0 Hz, CH2CHO, 2H), 2.50 (dt, 3J(H,H) = 7.0 Hz and 6.9

Hz, CH=CHCH2, 2H), 1.31 (d, 3J(H,H) = 7.0 Hz, (CH3)2CH, 6H); 13C{1H} NMR (101 MHz,

CDCl3, δ in ppm): 200.6 (s, CHO), 190.2 (s, CO), 141.9 (s, CH=CHCH2), 129.7 (s, CH=CHCH2),

41.8 (s, CH2CHO), 34.5 (s, (CH3)2CH), 24.3 (s, CH=CHCH2), 23.0 (s, (CH3)2CH).

IR (thin film, in cm–1):71 1725 (s, νCO), 1664 (s, νCO), 1629 (s, νC=C).

(E)-p-Tol(CO)CH=CHCH2CH2CH2CHO (C2(p-Tol)) was obtained (1:3 v/v ethyl

acetate/n-pentane) as a slightly yellow liquid (0.689 g, 3.19 mmol, 55%). Elemental analysis calcd

(%) for C14H16O2 (216.1): C 77.75, H 7.46; found: C 77.18, H 7.53.

1H NMR (400 MHz, CDCl3, δ in ppm): 9.80 (s, CHO, 1H), 7.84 (d, 3J(H,H) = 8.1 Hz, C6H4,

o to CO, 2H), 7.27 (d, 3J(H,H) = 8.1 Hz, C6H4, m to CO, 2H), 7.00 (dt, 3J(H,H) = 15.5 Hz and 6.8

Hz, CH=CHCH2, 1H), 6.32 (d, 3J(H,H) = 15.5 Hz, CH=CHCH2, 1H), 2.53 (t, 3J(H,H) = 7.5 Hz,

CH2CHO, 2H), 2.42 (s, CH3, 3H), 2.36 (dt, 3J(H,H) = 7.5 Hz and 7.5 Hz, CH=CHCH2, 2H), 1.88

(tt, 3J(H,H) = 7.5 Hz and 7.5 Hz, CH2CH2CHO, 2H); 13C{1H} NMR (101 MHz, CDCl3, δ in ppm):

202.0 (s, CHO), 190.4 (s, CO), 147.7 (s, CH=CHCH2), 143.9 (s, C6H4, p to CO), 135.6 (s, C6H4, i

to CO), 129.7, 129.1 (2 s, C6H4, o, m to CO), 127.0 (s, CH=CHCH2), 43.5 (s, CH2CHO), 32.3 (s,

CH=CHCH2), 22.1 (s, CH2CH2CHO), 20.9 (s, CH3).

IR (thin film, in cm–1):71 1722 (s, νCO), 1668 (s, νCO), 1621 (s, νC=C).

(E)-CH3O(CO)CH=CHCH2CH2CH2CHO (C2OMe)47 was obtained (1:1 v/v ethyl



the literature.

(E)-EtO(CO)CH=CHCH2CH2CH2CHO (C2OEt)25,49 was obtained (2:3 v/v ethyl


the literature.

(E)-Ph(CO)CH=CHCH2CH2CH2CHO (C2Ph)25 was obtained (3:7 v/v ethyl acetate/n-


literature.

(E)-CH3(CO)CH=CHCH2CH2CH2CHO (C2Me)44 was obtained (3:7 v/v ethyl acetate/n-


literature.

5.4.3.2 Rauhut Currier Substrates

(E,E)-R(CO)CH=CHCH2(CH2)nCH=CH(CO)R; general procedure. A flask was

charged with a solution of a dialdehyde (n = 1, succinaldehyde;48,111 2, glutaraldehyde112) in

CH2Cl2 (20.0 mL, 0.300 M, 6.0 mmol). Then the ylide R(CO)CHPPh3 (34a-f, 12.6 mmol)

dissolved in CH2Cl2 (5 mL) was added with stirring. After 24 h, the solvent was removed by rotary

evaporation. The products were purified by column chromatography (SiO2).

(E,E)-Ph(CO)CH=CHCH2CH2CH=CH(CO)Ph (C1Ph2)45 was obtained (1:1 v/v ethyl

acetate/n-pentane) as a white solid (0.974 g, 3.36 mmol, 56%). Analytical data agreed with that in

the literature.

(E,E)-p-Tol(CO)CH=CHCH2CH2CH=CH(CO)p-Tol (C1(p-Tol)2) was obtained (1:1 v/v

ethyl acetate/n-pentane) as a yellow solid (0.286 g, 0.900 mmol, 82%). M.p. 113.0-113.5 °C


(capillary). Elemental analysis calcd (%) for C22H22O2 (318.4): C 82.99, H 6.96; found: C 83.00, H

6.86.


7.27 (d, 3J(H,H) = 8.1 Hz, C6H4, m to CO, 4H), 7.06 (dt, 3J(H,H) = 15.3 Hz and 6.4 Hz,

CH=CHCH2, 2H), 6.96 (d, 3J(H,H) = 15.3 Hz, CH=CHCH2, 2H), 2.59-2.56 (m, CH=CHCH2, 4H),

2.43 (s, CH3, 6H); 13C{1H} NMR (101 MHz, CDCl3, δ in ppm): 189.9 (s, CO), 146.8 (s,

CH=CHCH2), 143.5 (s, C6H4, p to CO), 135.1 (s, C6H4, i to CO), 129.2, 128.6 (2 s, C6H4, o, m to

CO), 126.6 (s, CH=CHCH2), 31.2 (s, CH=CHCH2), 21.6 (s, CH3).

IR (thin film, cm–1):71 1664 (s, νCO), 1598 (s, νC=C).

(E,E)-CH3(CO)CH=CHCH2CH2CH=CH(CO)CH3 (C1Me2)50 was obtained (1:1 v/v

ethyl acetate/n-pentane) as a slightly yellow solid (0.398 g, 2.40 mmol, 40%). Analytical data

agreed with that in the literature.

(E,E)-i-PrS(CO)CH=CHCH2CH2CH=CH(CO)S(i-Pr) (C1(S-i-Pr)2) was obtained (1:9

v/v ethyl acetate/n-pentane) as a colorless solid (1.37 g, 4.80 mmol, 80%). M.p. 36.8-37.8 °C

(capillary). Elemental analysis calcd (%) for C14H22O2S2 (286.1): C 58.70, H 7.74, S 22.39; found:

C 58.35, H 7.55, S 22.25.

1H NMR (300 MHz, CDCl3, δ in ppm): 6.81 (dt, 3J(H,H) = 15.4 Hz and 6.1 Hz,

CH=CHCH2, 2H), 6.07 (d, 3J(H,H) = 15.4 Hz, CH=CHCH2, 2H), 3.69 (sept, 3J(H,H) = 7.0 Hz,

(CH3)2CH, 2H), 2.33 (d, 3J(H,H) = 6.1 Hz, CH=CHCH2, 4H), 1.31 (d, 3J(H,H) = 7.0 Hz,

(CH3)2CH, 12H); 13C{1H} NMR (101 MHz, CDCl3, δ in ppm): 189.8 (s, CO), 142.3 (s,

CH=CHCH2), 129.6 (s, CH=CHCH2), 34.5 (s, (CH3)2CH), 30.3 (s, CH=CHCH2), 23.0 (s,

(CH3)2CH).


(E,E)-H3C(CO)CH=CHCH2CH2CH2CH=CH(CO)CH3 (C2Me2)26 was obtained (1:1

v/v ethyl acetate/n-pentane) as a clear liquid (0.756 g, 4.20 mmol, 70%). Analytical data agreed

with that in the literature.


(E,E)-p-Tol(CO)CH=CHCH2CH2CH2CH=CH(CO)p-Tol (C2(p-Tol)2) was obtained (1:1

v/v ethyl acetate/n-pentane) as a slightly yellow solid (1.59 g, 4.79 mmol, 80%). M.p. 49-51 °C

(capillary). Elemental analysis calcd (%) for C23H24O2 (332.4): C 83.10, H 7.28; found: C 79.96, H

7.09.


7.26 (d, 3J(H,H) = 8.2 Hz, C6H4, m to CO, 4H), 7.05 (dt, 3J(H,H) = 15.4 Hz and 7.1 Hz,

CH=CHCH2, 2H), 6.92 (dt, 3J(H,H) = 15.4 Hz, 4J(H,H) = 1.0 Hz, CH=CHCH2, 2H), 2.42-2.35 (m,

CH=CHCH2, 4H), 2.41 (s, CH3, 6H), 1.78 (pen, 3J(H,H) = 7.3 Hz, CH=CHCH2CH2, 2H); 13C{1H}

NMR (101 MHz, CDCl3, δ in ppm): 190.1 (s, CO), 148.0 (s, CH=CHCH2), 143.5 (s, C6H4, p to

CO), 135.2 (s, C6H4, i to CO), 129.2, 128.6 (2 s, C6H4, o, m to CO), 126.4 (s, CH=CHCH2), 32.1 (s,

CH=CHCH2), 26.7 (s, CH=CHCH2CH2), 21.6 (s, CH3).


6

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List of Publications

"Synthesis and Properties of Fluorous Arenes and Triaryl Phosphorus Compounds with Branched

Fluoroalkyl Moieties ("Split Pony Tails")", Wende, M.; Seidel, F.; Gladysz, J. A. J. Fluorine Chem.

2003, 124, 45.

"Enantioselective Catalysis of Intramolecular Morita Baylis-Hillman and Related Reactions by

Chiral Rhenium-Containing Phosphines of the Formula (η5-C5H5)Re(NO)(PPh2)(CH2PAr2)",

Seidel, F.; Gladysz, J. A. Synlett 2007, 6, 986.

"Catalysis of Intramolecular Morita Baylis Hillman and Rauhut Currier Reactions by Fluorous

Phosphines; Facile Recovery by Liquid/Solid Organic/Fluorous Biphase Proctocols Involving

Precipitation, Teflon® Tape and Gore-Tex® Fibers", Seidel, F. O.; Gladysz, J. A. Adv. Synth. Catal.

2008, 350, 2443.

Curriculum Vitae

Persönliche Daten Florian O. Seidel

geboren am 12.04.1978 in Nürnberg

verheiratet

Schulbildung 1984 – 1988 Grundschule Herpersdorf b. Nürnberg

1988 – 1997 Pirckheimer-Gymnasium Nürnberg

Studium Okt. 1997 – Jan. 2004 Chemie (Diplom)

An der Friedrich-Alexander-Universität

Erlangen-Nürnberg

Nov. 2000 Diplomvorprüfung

Feb. 2004 Diplomhauptprüfung

Diplomarbeit März 2004 – Dez. 2004 Institut für Organische Chemie der

Friedrich-Alexander-Universität

Erlangen-Nürnberg

bei Prof. Dr. J. A. Gladysz

"A New Class of Catalysts for the Baylis

Hillman Reaction: Chiral Rhenium-Containing

Phosphines"

Dissertation Jan. 2005 – Dez. 2008 Institut für Organische Chemie der

Friedrich-Alexander-Universität

Erlangen-Nürnberg

bei Prof. Dr. J. A. Gladysz

"New Design Strategies for Phosphine

Organocatalysts: Enantioselective Processes

involving Chiral Rhenium Fragments and

Recycling involving Perfluorinated Pony Tails"

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