Frustrated Lewis Pair Catalysts for Asymmetric ...

"Frustrated Lewis Pair Catalysts for Asymmetric Hydrogenation, Hydrosilylation and Hydroboration

Reactions"

Von der Fakultät für Mathematik, Informatik und Naturwissenschaften der RWTH Aachen University

zur Erlangung des akademischen Grades eines Doktors der Naturwissenschaften genehmigte

Dissertation

vorgelegt von

MSc.

Ghazi Ghattas

aus Barja, Libanon

Berichter: Junior professor, Dr.rer. nat. Jürgen Klankermayer

Universitätsprofessor, Dr. Walter Leitner

Universitätsprofessor, Dr. Meike Niggemann

Tag der mündlichen Prüfung: 2. Februar 2016

Diese Dissertation ist auf den Internetseiten der Universitätsbibliothek online verfügbar

i

The present doctoral Thesis was carried out at the Institut für Technische und Makromolekulare

Chemie at the RWTH Aachen University (Rheinisch-Westfälische Technische Hochschule Aachen)

under the supervision of Junior professor, Dr.rer. nat. Jürgen Klankermayer, from September 2010 to

December 2014.

Affidavit

I hereby declare that I wrote this work independently and only the specified sources and recourses

were used. This work has not been presented to any examination office. Part of the work has been

published (see list of publications and conference contributions).

Eidesstattliche Erklärung

Hiermit erkläre ich, dass ich diese Arbeit eigenständig verfasst und nur die angegebenen Quellen und

Hilfsmittel verwendet habe. Die Arbeit wurde bisher keiner Prüfungsbehörde vorgelegt. Teile der

Arbeit wurden bereits veröffentlicht (siehe Liste der Publikationen und Konferenzbeiträge).

ii

Selected results from this thesis were already published:

1. Asymmetric hydrogenation of imines with recyable chiral frustrated Lewis pair catalyst

G. Ghattas, D. Chen, J. Klankermayer Dalton Trans. 2012, 41, 9026-9028.

2. Ruthenium-Catalyzed Reductive Methylation of Imines Using Carbon Dioxide and

Molecular Hydrogen. K. Beydoun, G. Ghattas, K. Thenert, J. Klankermayer and W.

Leitner, Angew. Chem. Int. Ed. 2014, 53, 11010-11014.

iii

Abstract

Asymmetric catalysis using molecular transition metal complexes represents an important

synthetic tool in basic research and industrial chemistry. The recent development of frustrated

Lewis-pair catalysts (FLP) enabled the possibility to perform these transformations with

metal-free systems. This thesis describes the synthesis of novel chiral FLP catalysts and their

application in selected asymmetric hydrogenation, hydrosilylation and hydroboration

reactions.

In the first part of the thesis, the development of new chiral boranes derived from (R)-

Camphor is presented, with a detailed focus on the stability and recyclability of the respective

FLP catalysts. Based on these catalysts the enantioselective hydrogenation of various imines

to the corresponding amines could be achieved with an enantiomeric excess up to 83 % ee.

Moreover, the novel FLP structures allowed reusing the catalysts in consecutive reactions at

constant enantioselectivity.

In the second part of the thesis, metal-free asymmetric hydrosilylation and hydroboration

reactions were investigated. In the hydrosilylation of imines an enantiomeric excess up to 88

% ee could be achieved using novel tailored FLP catalysts. The subsequent application of

these FLP catalysts in the asymmetric hydroboration was challenging and additional

information on the respective reaction mechanisms had to be obtained, to guide the catalytic

experiments and the catalyst optimization. Consequently, detailed NMR spectroscopic

investigations paved the way towards an efficient catalysts system and up to 80 % ee could be

achieved in the hydroboration of selected imines. However, the future applicability of these

metal-free catalysts strongly depends on the synthetic accessibility of versatile borane

reagents, the important part of the FLP system. Therefore, a novel synthetic pathway to

HB(C6F5)2 and HB(p-C6F4H)2 starting from low cost and non-toxic starting materials could be

established, avoiding laborious preparation steps and enabling the multigram scale preparation

of the respective important boranes.

iv

Acknowledgement

Over the past four years I have learned that a graduate degree is not a path travelled alone, but

one travelled in the company of many. I am indebted to my supervisor Prof. Dr. Jürgen

Klankermayer for fruitful discussions, moral support, suggestions and the constant

encouragement to believe in myself. Prof. Dr. Walter Leitner for giving me the opportunity to

join the group and the excellent research facilities at the institute. I would like to thank the

Research cluster SusChemSys for all the interesting workshops and meetings with our

industrial partners. My lab colleagues, both past and present, I would like to thank for the

constant support, jokes, and friendship. In particular I would like to acknowledge Dr. Dianjun

Chen who was an inspiring mentor, who introduced me to this interesting topic and to whom I

owe a considerable degree of my success. I would like to thank Dr. Tim den Hartog for

dedicating time to review this thesis. Finally my parents, brother, two sisters and Rabih

Sleiman are my greatest supporters. When I was doubtful, you offered words of support and

encouragement and celebrated with me in my successes. I love and thank you all.

v

Table of Contents Abstract .................................................................................................................................................. iii

Acknowledgement .................................................................................................................................. iv

1. Introduction ......................................................................................................................................... 1

2. Objective of the present work............................................................................................................ 10

3. Results and Discussion ...................................................................................................................... 11

3.1. Enantioselective hydrogenation with chiral FLP catalysts ......................................................... 11

3.1.1 Introduction .......................................................................................................................... 11

3.1.2 Development of novel chiral intramolecular FLP catalysts ................................................. 12

3.1.3 Catalyst recycling experiment .............................................................................................. 17

3.1.4 Selected structural modifications of the Lewis acid in chiral FLP system ........................... 17

3.1.5 FLPs system with two Lewis acidic sites ............................................................................. 22

3.1.6 Application of the novel Lewis acid 31 and 36 in the asymmetric hydrogenation of imines

....................................................................................................................................................... 32

3.1.7 Conclusion ............................................................................................................................ 34

3.1.8 Established synthetic procedure for the preparation of perfluroaryl boranes ....................... 36

3.1.9 Novel synthesis pathways to the versatile Lewis acids HB(C6F5)2 and HB(p-C6F4H)2 ....... 38

3.1.10 Conclusion .......................................................................................................................... 39

3.2 Enantioselective Hydrosilylation and Hydroboration of Imines ................................................. 40

3.2.1 Introduction .......................................................................................................................... 40

3.2.2 Enantioselective Hydrosilylation of imines using FLPs catalysts ........................................ 43

3.2.3 Metal-catalyzed asymmetric hydroboration ......................................................................... 45

3.2.4 Enantioselective hydroboration of imines in presence of chiral boranes ............................. 47

3.2.5 Mechanistic investigation on the enantioselective hydroboration with chiral FLP catalysts 49

3.2.6 Proposed mechanism for enantioselective hydroboration of imines using Frustrated Lewis

Pair ................................................................................................................................................ 52

3.2.7 Enantioselective hydroboration of imine 17 in presence of selected chiral FLPs catalysts . 54

3.2.8 Enantioselective hydroboration of selected imines using chiral catalyst 3 .......................... 55

3.2.9 Conclusion ............................................................................................................................ 56

4. Conclusion ......................................................................................................................................... 58

5. Experimental part: ............................................................................................................................. 61

5.1 General ........................................................................................................................................ 61

5.2 Synthesis ...................................................................................................................................... 62

5.2.1 Synthesis of bis(pentafluorophenyl)borane HB(C6F5)2:[25]

................................................... 62

5.2.2 Synthesis of bis(tetrafluorophenyl)borane (p-C6F4H)2BH:[27]

.............................................. 63

vi

5.2.3 Synthesis of (1R,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-en-2-yltrifluoromethanesulfonate

(5):[66]

............................................................................................................................................. 64

5.2.4 Synthesis of 2-[(1R,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-en-2-yl]pyridine (6):[66]

........ 65

5.2.5 Synthesis of 2-[(1R,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-en-2-yl]quinoline (8):[67]

...... 66

5.2.6 Synthesis of (1R, 4R)-2-(4-bromophenyl)-1,7,7-trimethyl-2-phenylbicyclo[2.2.1]hept-2-ene

(11):[24]

........................................................................................................................................... 67

5.2.7 Synthesis of di-mesityl(4-((1S,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-en-2-

yl)phenyl)phosphine (12): ............................................................................................................. 68

5.2.8 Synthesis of di-mesitylphoshine bis(perfluorophenyl)((1R,2R,3R,4S)-4,7,7-trimethyl-4-

phenyl-bicyclo[2.2.1]heptan-2-yl)hydroborate (13): ..................................................................... 69

5.2.9 Synthesis of di-tert-butyl(4-((1R,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-en-2yl)-

phenyl)phosphine (14):[36]

............................................................................................................. 70

5.2.10 Synthesis of di-tert-butylphosphonium bis(perfluorophenyl) ((1R,2R,3R,4S)-4,7,7-

trimethyl-4-phenyl-bicyclo[2.2.1]heptan-2-yl) hydroboratborate (16):[36]

.................................... 71

5.2.11 X-Ray Single crystal analysis of 16:[36]

.............................................................................. 72

5.2.12 Synthesis of (1R,4R)-1,7,7-trimethyl-2-(2-naphthyl)-bicyclo[2.2.1]hept-2-ene (24):[20]

... 73

5.2.13 Synthesis of bis(perfluorophenyl)((1R,2R,3R,4S)-4,7,7-trimethyl-3-(naphthalen-2-

yl)bicyclo[2.2.1]heptan-2-yl)borane (27).[20]

................................................................................. 74

5.2.14 Synthesis of bis(perfluorophenyl)((1R,2R,3R,4S)-4,7,7-trimethyl-3-(naphthalen-2-

yl)bicyclo[2.2.1]heptan-2-yl)hydroborate tri-tert- butylphosphonium salt (3):[20]

........................ 75

5.2.15 Synthesis of (2,3,5,6-tetrafluorophenyl)((1R,2R,3R,4S)-4,7,7-trimethyl-3-(naphthalen-2-

yl)bicyclo[2.2.1]heptan-2-yl)borane, tri-tert-butylphosphonium salt (26): ................................... 76

5.2.16 X-Ray Single crystal analysis of 26: .................................................................................. 77

5.2.17 Synthesis of 1,1'-(4,4'-((4,7,7-trimethyl-3-(naphthalen-2-yl)bicyclo[2.2.1]heptan-2-

yl)boranediyl)bis(2,3,5,6-tetrafluoro-4,1phenylene)) bis((2R,5R)2,5dimethylphospholane) (28): 78

5.2.18 Synthesis of 1-((1S,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-en-2-yl)-4-((1S,4R)-1,7,7-

trimethylbicyclo[2.2.1]hept-2-en-2-yl)benzene (30): .................................................................... 79

5.2.19 Synthesis of para-di-bis(perfluorophenyl)((1R,2R,3R,4S)-4,7,7-trimethyl-3-(phenyl-2-

yl)bicyclo[2.2.1]heptan-2-yl)borane (31): ..................................................................................... 80


5.2.21 Synthesis of di-tri-tert-butylphosphonium para-di-bis(perfluorophenyl)((1R,2R,3R,4S)-

4,7,7-trimethyl-3-(phenyl-2-yl)bicyclo[2.2.1]heptan-2-yl)hydroborate (32). ............................... 82


5.2.23 Synthesis of (1S,4R)-2-(3-bromophenyl)-1,7,7-trimethylbicyclo [2.2.1]hept-2-ene (33): . 84

5.2.24 Synthesis of 1-((1R,4S)-1,7,7-trimethylbicyclo[2.2.1]hept-2-en-2-yl)-3-((1S,4R)-1,7,7-

trimethylbicyclo[2.2.1]hept-2-en-2-yl)benzene (35): .................................................................... 85

5.2.25 Synthesis of meta-di-bis(perfluorophenyl)(1R,2R,3R,4S)-4,7,7-trimethyl-3-(phenyl-2-

yl)bicyclo[2.2.1]heptan-2-yl) borane (36): .................................................................................... 86


vii

5.2.27 Synthesis of di-tri-tert-butylphosphonium meta-di-bis(perfluorophenyl)((1R,2R,3R,4S)-

4,7,7-trimethyl-3-(phenyl-2-yl)bicyclo[2.2.1]heptan-2-yl)hydroborate (37). ............................... 88

5.3.1 General procedure for the catalytic hydrosilylation of imines ............................................. 89

5.3.2 General procedure for the catalytic hydrogenation of imines .............................................. 89

5.3.3 Catalyst 16 recycling experiments procedure ....................................................................... 89

5.3.4 General procedure for the catalytic hydroboration of imines ............................................... 89

5.3.5 Monitoring hydroboration reaction of imine 17 using PinBH as hydroborating reagent ..... 90

5.3.6 Monitoring hydroboration reaction of imine 17 using CatBH as hydroborating reagent ..... 92

5.3.7 Monitoring hydroboration reaction of imine 17 using CatBH with catalyst 3 and excess

amount of t-Bu3P (cat.3 : t-Bu3P / 1:4) .......................................................................................... 94

5.3.8 Hydroboration of imine 17 using CatBH ............................................................................. 95

5.3.9 Monitoring hydroboration reaction of imine 17 using CatBH with catalyst 27 ................... 96

6. Appendix ........................................................................................................................................... 98

6.1 Selected NMR spectra ................................................................................................................. 98

Curriculum Vitae ................................................................................................................................. 115

1

1. Introduction

The Lewis acid/base theory has been widely and successfully used to explain and predict

chemical reactivity.[1]

A Lewis acid is defined as an electron pair acceptor, and a Lewis base

as an electron pair donor.[1]

Lewis acid and Lewis base pairs tend to undergo neutralization

reactions, resulting in Lewis acid/base adducts as products (Scheme 1).[2]

Scheme 1. Classical Lewis acid/Lewis base adduct formation.

In detailed studies the electronic effects of both Lewis-partners on reactivity were explored,

but the influence of steric factors remained rather unclear. In 1942, Brown and co-workers

initiated a study on the influence of steric strain on Lewis base pairs and found that the

repulsion of two parts decreased the bond strength between them.[3]

Moreover, Lewis

acid/base adduct formation could be significantly hindered or even prevented by selecting

suitable combinations.[4]

In the following decades, detailed studies were reported to perceive

the role and influence of steric strain on the reactivity and stability of the Lewis acid/base

pairs and their use in organic synthesis.[5]

The synthesis of compounds with Lewis acid and Lewis base sites in one molecule is

considered a challenge due to the fast formation of the corresponding Lewis acid/base adduct.

However, these compounds are highly interesting as they could act as trap for reactive

molecules or as storage compounds, due to the synergetic effects of the neighboring electron

acceptor and electron donor sites. In 2003, Piers and co-workers reported the synthesis of an

ortho-phenyl bridged 1-(NPh2)-2-[B(C6F5)2]C6H4 amino borane and the Lewis acid/base

adduct formation could be avoided by selecting suitable Lewis acid/base combinations

(Scheme 2).[6]

This compound could trap H2O and HCl, generating the corresponding

zwitterionic compounds (Scheme 2).[6]

2

Scheme 2. Piers amino-borane.[6]

Three years after the report of Piers, Stephan and co-workers described a system where the

Lewis acid and Lewis base sites were widely separated to avoid generation of Lewis acid/base

adducts.[7]

In detail, the reaction between tris(pentafluorophenyl)borane (B(C6F5)3) and

dimesitylphosphine (Mes2PH) generated the zwitterionic compound A (Scheme 3).

Subsequent treatment with chlorodimethylsilane (Me2SiHCl) replaced fluoride, resulting in B.

The phosphonium borate compound B showed unpresented reactivity and was able to liberate

H2 at high temperature (over 100 °C), resulting in compound C.[7]

In the presence of H2 the

Lewis acidity and Lewis basicity were strong enough to heterolytically cleave H2 and to

regenerate the thermodynamically stable zwitterion B. Consequently, due to the steric effect

preventing formation of the Lewis acid/base adduct, the Lewis acid and Lewis base were

highly reactive. This discovery was the first metal-free catalytic system which was able to

activate H2 in a reversible manner and this type of compounds was termed Frustrated Lewis

Pairs (FLP).[7]

3

Scheme 3. Reversible hydrogen activation by FLPs.[7]

Subsequently, first examples of FLPs were used as catalysts for selected hydrogenation

reactions.[8]

The first metal-free catalyst for the hydrogenation of imines was reported by

Stephan, using the FLPs Mes2PHC6F4BH(C6F5)2 and its analogue t-Bu2PHC6F4BH(C6F5)2 as

catalyst.[9]

Mechanistic studies indicated, that the initial step (I) is a proton transfer from the

catalyst to the nitrogen atom of the imine, followed by a hydride transfer to the carbon of the

imine (II), liberating the amine product and reforming the corresponding Lewis pair. The

Lewis pair is able to regenerate the zwitterionic catalyst under a H2 atmosphere (Scheme 4).

The phosphoborane catalyst was able to reduce bulky imines in high yields at moderate

reaction temperatures, [9]

but the catalytic reduction of less hindered imines and nitriles could

be not observed. In this reaction, the formation of a very strong Lewis adduct of the boron

compound with the nitrogen-containing substrates was observed.

4

Scheme 4. Catalytic hydrogenation mechanism of imines with FLP catalysts.[9]

Later, the intermolecular FLP concept could be reported by Stephan and co-workers, using

only tri-tert-butylphoshine (t-Bu3P) or trimesitylphosphine (Mes3P) as Lewis base and

B(C6F5)3 as Lewis acid. This combination enabled the heterolytic cleavage of molecular

hydrogen, resulting in the corresponding zwitterion (Scheme 5).[10]

Scheme 5. Intermolecular hydrogen cleavage with FLPs.[10]

Surprisingly, hydrogenation reactions using only the Lewis acid B(C6F5)3 enabled the

transformation of less hindered imines and nitriles. In this case no additional base was

required, as the substrate could also act as the Lewis base within the FLP.[11]

Later, the use of

the substrate as Lewis base was further studied using phosphines, nitrogen and carbon derived

bases.[8d, 12]

Furthermore, extensive fine tuning of the Lewis acid/base pairs enabled the

discovery of numerous reversible H2 activation systems with wide applications.[8a, 8d]

5

In 2007, Erker and co-workers reported a new ethylene linked phosphonium borate as highly

active catalyst for the hydrogenation of imines at room temperature (Scheme 6).[13]

The high

reactivity was assigned to the exceptional structural constraints that allowed the Lewis acid

and base to perform a weak interaction. At 25 °C and at a H2 pressure of 1.5 bar, various

imines were catalytically reduced to the corresponding amines.[13]

This weak interaction in the

FLP could detain the product amine from interacting with the boron center and therefore the

phosphino-borane enabled facile H2 activation in a catalytic fashion, resulting in fast

regeneration of the catalyst. In a similar manner, different enamines could be hydrogenated to

the corresponding amines.[14]

Scheme 6. Ethylene linked phosphino-borane FLP system.[14a]

In 2012, Stephan and Paradies reported the first metal-free olefin hydrogenation catalyst.[15]

In

this reaction the choice of the Lewis base in combination with the classical Lewis acid

B(C6F5)3 was a critical parameter. Weakly basic phosphines in combination with B(C6F5)3

allowed the hydrogenation of selected olefins (Scheme 7a).[15]

Later in 2013, Repo and co-

workers reported a highly chemo- and stereoselective catalytic hydrogenation of alkynes to

cis-alkenes using an ansa-aminohydroborane FLP catalyst (Scheme 7b).[16]

6

Scheme 7. Catalytic hydrogenation of alkynes to cis-alkenes using ansa-aminohydroborane FLP catalyst.[16]

Based on the development of highly reactive FLP catalysts, enantioselective transformations

with metal-free catalyst were investigated. In early experiments chiral Lewis base moieties

such as (R)-binap, (S,S)-chiraphos, (S,S)-diop were used to induce enantioselectivity in

asymmetric transformations. The group of Stephan investigated the effect of chiral

phosphines as Lewis basic moiety in combination with the classical Lewis acid B(C6F5)3 on

the FLP catalyzed hydrogenation of prochiral imines, and moderate selectivities up to 25 % ee

were obtained (Scheme 8).[17]

Scheme 8. Enantioselective hydrogenation of imines with FLPs based on B(C6F5)3/chiral phosphine

combinations.[17]

Based on the same principle, Repo and co-workers designed the chiral intramolecular FLP

(TMPNH)-CH2C6H4B(C6F5)2 via the incorporation of a chiral amine into the backbone of a

tweezer-like amino-borane catalyst (Scheme 9).[18]

The subsequent catalytic hydrogenation

demonstrated the chiral FLP as active catalyst for the reduction of imines and substituted

quinolones in moderate enantiomeric excess (up to 37 % ee).[18b]

7

Scheme 9. Enantioselective hydrogenation of imines with a catalyst based on ansa-amino-borane FLPs. [18b]

In a different strategy the application of chiral boranes in the asymmetric hydrogenation was

investigated. Based on the established methods for imine hydrogenation, the stereoselective

hydride transfer from the hydrido-borate could form a chiral carbon center with higher

selectivity. In 2010, Chen et al. reported a new camphor-based chiral borane. This borane was

obtained as diastereoisomeric mixture, the (1R, 2S, 3S, 4S) [(S)-camphor] and (1R, 2R, 3R, 4S)

[(R)-camphor] compounds (Step A) (Scheme 10). In the presence of t-Bu3P as Lewis base, H2

is activated and the diastereoisomeric phosphonium hydridoborate compounds are obtained

(Step B) (Scheme 10). Enantioselective hydrogenation of prochiral N-(1-phenyl-

ethylidene)aniline using a mixture of the diastereoisomers in a 1:1 ratio gave enantiomeric

excess up to 20 % ee.[19]

In order to achieve high selectivity, the two diastereoisomers were separated based on their

reactivity towards H2. The (S)-diastereoisomer reacts faster with H2 and precipitated from

solution. Enantioselective hydrogenation of N-(1-phenyl-ethylidene)aniline using only the (S)

-configurated diastereoisomer afforded the corresponding amine with an ee of 48 %. The (R)-

isomer gave a higher selectivity of up to 79 % ee.[19]

Subsequently, the aim was to obtain only

the more selective (R)-isomer compound. When a mixture of (R)- and (S)-diastereoisomers

were heated up to 100 °C for a specific time, the (S)- compound transforms to the (R)- isomer,

the thermodynamically favored product (Step C) (Scheme 10). In the presence of t-Bu3P as

Lewis base, H2 activation was successful and only the (R)- phosphonium hydridoborate

compound was obtained (Step D) (Scheme 10).

8

Scheme 10. New synthetic pathways to the camphor based chiral FLP catalyst.[19]

In addition to the enantioselective hydrogenation of imines, Chen et. al reported in 2012 an

alternative way to obtain amine products starting from imine substrates via enantioselective

hydrosilylation.[20]

Dimethylphenylsilane was used as the hydrosilylation reagent in the

presence of 5 mol % of FLP catalyst, resulting in the corresponding N-(1-phenyl-

ethylidene)aniline product with an enantiomeric excess up to 83 % ee (Scheme 11).[20]

Scheme 11. Enantioselective hydrosilylation of N-(1-phenylethy-lidene)aniline.[20]

In 2013, Du and co-workers investigated the asymmetric hydrogenation of imines employing

a chiral catalyst based on binaphthyl-structure. The active catalyst was generated in situ by

hydroboration of acyclic dienes with bis(pentafluorophenyl)borane HB(C6F5)2. Different

9

chiral dienes were tested based on the modification of the 3,3´-position of the binaphthyl-unit

and the steric bulk of the aryl substituent had a strong impact on enantioselectivity. Under

optimized conditions, an in situ generated chiral diene was able to hydrogenate imines with

selectivities up to 89 % ee (Scheme 12).[21]

Scheme 12. In situ formed chiral boranes for asymmetric hydrogenation of imines.[21]

10

2. Objective of the present work

The possibility to activate molecular hydrogen using Frustrated Lewis pairs was introduced

by Stephan in 2006.[7]

In the following years efficient catalysts for the application in

homogeneous reactions could be established and asymmetric transformation were enabled

with the application of chiral Lewis acids.

The main objective of the work is to develop novel chiral metal-free frustrated Lewis pair

catalysts for enantioselective transformations. In this development the subtle interplay of

Lewis acidity and basicity in combination with the steric environment of the catalyst are

essential design factors towards the creation of effective FLP systems. Consequently, the

catalyst development for hydrogenation, hydrosilylation and hydroboration reactions should

be rationally guided by detailed mechanistic studies and NMR spectroscopic investigations.

Furthermore, the recyclability of the chiral metal-free catalyst will be an important factor for

future applications and should be thoroughly optimized within these investigations.

11

3. Results and Discussion

3.1. Enantioselective hydrogenation with chiral FLP catalysts

3.1.1 Introduction

The first example of enantioselective hydrogenation of imines using FLP catalysts was

reported in 2008. The Pinene-derived chiral borane catalyst 1 (Figure 1) was able to

hydrogenate prochiral imines with enantioselectivity up to 13 % ee.[11b]

In 2010, Chen et. al

reported the new chiral FLP catalyst 2 (Figure 1) that enabled enantioselective hydrogenation

of selected prochiral imines with enantioselectivities up to 83 % ee.[19]

Subsequently, an

optimised chiral catalyst 3 was reported for the enantioselective hydrosilylation of imines and

87 % ee could be obtained.[20]

Catalysts 2 and 3 are sensitive towards oxygen or moisture, and

consequently the catalyst activity is lost after a first recycling attempt.

Figure 1. Chiral FLP catalysts for asymmetric hydrogenation

Stephan and co-workers already reported a FLP catalyst combining the Lewis acid and Lewis

base in one molecule.[7]

With this system the heterolytic cleavage of H2 via the formation of a

phosphonium borate zwitterion was successful and this compound was to some extent air and

moisture tolerant. Heating the phosphonium borate zwitterion to 150 °C prompted the

elimination of H2, regenerating the phosphine-borane.[7]

In 2007, an ethylene linked

phosphonium borate intramolecular FLP was reported by the groups of Erker and Stephan.[13]

This metal-free intramolecular system was a highly effective catalyst for hydrogenation of

various unsaturated substrates.[14a]

[22]

Based on this principle, Rieger and Repo described in

2011 an air and moisture stable intramolecular FLP systems with a chiral ansa ammonium

borate structure, foreshadowing the extended applicability of these systems. Moreover, this

ansa ammonium borate catalyst hydrogenated imines with a moderate catalyst loading and

enantiomeric excess up to 37 % ee could be obtained.[23]

12

Having developed the highly enantioselective chiral intermolecular FLPs catalysts 2 and 3, an

increased stability and recyclability of the catalyst should be achieved with the camphor-lead

structure, by combining the Lewis acid and Lewis base in one chemical structure.

3.1.2 Development of novel chiral intramolecular FLP catalysts

A first attempt to achieve the synthesis of the chiral intramolecular FLP catalyst was

grounded on the previously reported camphor-based chiral FLP catalyst 2.[19]

The

commercially available (1R)-(+)-camphor 4 was treated with N-

phenyltrifluoromethanesulfonimide to afford the desired alkenyl triflate 5. To synthesize the

desired 2-alkenylpyridine 6, the chiral alkenyl triflate 5 was reacted with 2-pyridylzinc

bromide via a Negishi cross-coupling. However, the hydroboration step using HB(C6F5)2 to

generate the chiral borane was not successful and instead Lewis acid/base adduct 7 was

formed (Scheme 13). Increasing the temperature did not break this strong interaction and so

the desired FLPs compounds could not be constructed via this route.

Scheme 13. Attempted of intramolecular FLP system with pyridine unit

Replacing the pyridine moiety of 6 with a bulkier quinoline group enabled the synthesis of

Lewis base 8. However, the hydroboration step using HB(C6F5)2 was not successful and again

Lewis acid/base adduct 9 was formed (Scheme 14).

13

Scheme 14. Attempted of intramolecular FLP system with quinoline unit.

Increasing the distance between the Lewis acid and Lewis base within the same molecule is

one of the options to avoid Lewis acid/base adduct formation. Thus the hydrogen in para

position in the phenyl ring should be replaced by a Lewis basic moiety (Figure 2).

Figure 2. New intramolecular FLP design.

The synthesis strategy of the intramolecular FLP was similar to the synthesis of the already

established chiral FLP catalyst 2 (Scheme 15).[19]

Reaction of (1R)-(+)-camphor with in situ

generated (4-bromophenyl)magnesium bromide gave the corresponding tertiary alcohol 10.

Subsequent dehydration using a mixture of thionyl chloride and pyridine resulted in (1R, 4R)-

2-(4-bromophenyl)-1,7,7-trimethyl-2-phenylbicyclo[2.2.1]hept-2-ene 11 in 45 % yield.[24]

Lithiation using t-BuLi and nucleophilic substitution with di-mesityl-chlorophosphine

afforded di-mesityl-(4-((1R,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-en-2yl)-phenyl)phosphine

12. Hydroboration of 12 using HB(C6F5)2 successfully provided the diastereomerically pure

borane 13.[25]

Unfortunately H2 activation at room temperature and ambient pressure using 13

was not successful.

14

Scheme 15. Synthesis of chiral intramolecular FLP catalyst 13.

Consequently, the synthesis of the P(t-Bu)2 analogue was planned according to the same

synthetic procedure. Lithiation using t-BuLi and nucleophilic substitution with di-tert-

butylchlorophosphine afforded di-tert-butyl(4-((1R,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-

en-2yl)-phenyl)phosphine 14 (Scheme 16). Hydroboration of the unsaturated compound using

HB(C6F5)2 in n-pentane at 100 °C provided the diastereomerically pure borane 15, that was

used without further purification for H2 activation at room temperature and ambient

pressure.[25]

The resulting phosphonium hydridoborate compound 16 could be effectively

purified using column chromatography with dichloromethane as eluent, indicating an

increased stability towards moisture and oxygen in comparison to the chiral metal-free

catalysts 2 and 3 (Scheme 13). After purification the solvent was removed and compound 16

could be isolated as a colourless powder in 40 % yield. Phosphonium hydrido borate 16 could

be fully characterized by multinuclear NMR analysis. The 31

P{1H}-NMR spectrum of 16

revealed a singlet resonance at δ = 53.6 ppm, and the 19

F {1H}-NMR spectrum showed two

sets of signals for the diastereotopic C6F5 rings [δ = (ortho) -132.36 (d, JF-F = 21.9 Hz, 2F),

(ortho) -132.83 (m, 2F), (para) -165.73 (t, JF-F = 23.4 Hz, 1F), (para) -165.93 (t, JF-F = 20.8

Hz, 1F), (meta) -167.61 (m, 2F), (meta) -167.82 (m, 2F)]. In the 1H-NMR spectrum a broad

signal at 2.85 ppm corresponding to the BH bond and a doublet at 5.71 ppm (JP-H = 477 Hz)

for the PH bond could be observed, while the 11

B-NMR spectrum displayed a doublet at δ = -

19.25 ppm (JB-H = 81.6 Hz).

15

Scheme16. Synthesis of chiral intramolecular FLP compound 16.

Crystallisation of compound 16 in a mixture of dichloromethane and n-pentane resulted in

crystals suitable for X-ray crystallographic analysis. The analysis showed two independent

molecules in the unit cell with identical absolute configuration (1R, 2R, 3R, 4S) and one of

these structures is shown in Figure 3. Based on this information a distance of 7.77 Å between

the Lewis acid and Lewis base centre was calculated, avoiding the direct Lewis acid/base

adduct formation.

Figure 3. Molecular structure of FLP 16 in the crystal. Hydrogen atoms and solvent molecules were omitted for

clarity, except for the hydrogen atoms bound to boron and phosphorus. Distance between P1 and B1 atoms is

7.77 Å.

16

With the new chiral intramolecular FLP compound 16 in hand, enantioselective

hydrogenation reactions with selected prochiral imines were performed (Table 1). With 2 mol

% of catalyst 16 at 65 °C, 25 bar hydrogen pressure and 48 hours reaction time, imines 17, 18,

and 19 were hydrogenated with a conversion of 70 %, 51 % and 33 %. The obtained

enantiomeric excess was 72 %, 76 % and 72 % ee respectively (Table 1, entries 1-3).

Extending the reaction time from 48 to 72 hours for imine 17 increased the conversion to 90

% with comparable enantioselectivity (Table 1, entry 4). The methoxy substituted imines 20

and 21 were more active substrates for hydrogenation and full conversion was obtained within

48 hours and a selectivity ranging from 73 % to 76 % ee (Table 1, entries 5 and 6). Full

conversion was achieved within only 24 hours of reaction time at a notable enantioselectivity

of 76 % ee with the substrate incorporating two methoxy substituents 22 (Table 1, entry 7).

Replacing a methoxy function with a chlorine group, the conversion of 23 was slightly lower

(70 %), while the corresponding product was obtained in 72 % ee (Table 1, entry 8).

Table 1. Enantioselective hydrogenation of imines using chiral intramolecular FLP 16.

Entry[a]

Substrate Conversion

[%][d]

Isolated Yield

[%] ee [%]

[e]

1 17 70 63 72 (R)

2 18 51 32 76 (-)

3 19 33 21 72 (-)

4[b]

17 90 79 72 (R)

5 20 >99 95 73 (R)

6 21 >99 94 76 (+)

7[c]

22 >99 95 76 (+)

8

23 70 51 72 (+)

[a] Reaction conditions: catalyst loading (2.0 mol %), imine (0.5 mmol), H2 (25 bar), 1

mL toluene, T = 65 °C, 48 hours; [b] Reaction time: 72 hours; [c] Reaction time: 24 hours;

[d] Conversion was determined by 1H NMR analysis; [e] % ee was determined by HPLC

or GC methods using a chiral column; absolute configurations were assigned by

comparison of retention times and optical rotations with literature values.

17

3.1.3 Catalyst recycling experiment

The recyclability of catalyst 16 was investigated in more detail for the hydrogenation of imine

22 (Table 2). After the first hydrogenation experiment catalyst 16 was precipitated under air

with pentane, the supernatant solution was separated and analysed, showing full conversion of

the corresponding amine with 76 % ee (Table 2, entry 1). The recycled solid catalyst 16 was

subsequently transferred again to the autoclave, mixed with toluene and substrate, and

pressurized with 25 bar hydrogen. Four consecutive runs demonstrated a constant

enantioselectivity of 76 % ee and full conversion, confirming the effectiveness and stability of

the novel chiral intramolecular FLP catalyst 16 (Table 2, entries 1-4). As a result of catalyst

leaching or deactivation, in the fifth run the conversion decreased to 70 %, whereas the

enantioselectivity did not change (Table 2, entry 5).

Table 2. Recycling experiments with catalyst 16 and imine 22.

Entry[a]

Run Conversion [%][b]

ee [%][c]

1 1 >99 76 (+)

2 2 >99 76 (+)

3 3 >99 76 (+)

4

4 >99 76 (+)

5 5 70 76 (+)

[a] Reaction conditions: catalyst loading (2.5 mol %), H2 (25 bar), imine 22 (1.42 mmol), 1

mL toluene, T = 65 °C, 24 hours; [b] Conversion was determined by 1H NMR analysis; [c]

% ee determined by HPLC, absolute configuration was assigned by comparison of

retention times and optical rotation with literature values.

3.1.4 Selected structural modifications of the Lewis acid in chiral FLP system

The FLP methodology is based on the tailored interplay of the Lewis acid and the Lewis base

partners. Having the selective camphor-derived chiral catalyst 2 as a lead structure, we

decided to investigate the influence of various Lewis bases on FLP activity. In the novel

approch t-Bu3P was replaced with chiral Lewis bases such as (R)-BINAP, (S)-BINAP, (S)-

Tol-BINAP, and (R)-Tol-BINAP. However, no influence with respect to the enantiomeric

excess was observed (Table 3, entries 1-4). Increasing the temperature from 65 °C to 100 °C

resulted in a lower enantioselectivity of 77 % ee vs. 59 % ee (Table 3, entries 4-5). Lowering

the temperature to 50 °C showed a significant increase in terms of enantioselectivity, but the

conversion decreased to 40 % (Table 3, entry 6). Based on these results we concluded that the

18

chiral Lewis base does not alter the enantiomeric excess obtained during the hydrogenation

reaction of imines using FLP catalysts. From these experiments it can be further concluded

that the chirality in the Lewis acid and not the chiral Lewis base was mainly responsible for

the significant enantiomeric excess obtained in the hydrogenation of imines.[11b, 17]

Table 3. Effect of Lewis base modification.

Entry[a]

LB Temp. [°C]

Conversion [%][b]

ee [%][c]

1 (R)-BINAP 65 65 76 (R)

2 (S)-BINAP 65 50 78 (R)

3 (R)-tol-BINAP 65 30 77 (R)

4

(S)-tol-BINAP 65 39 77 (R)

5 (S)-tol-BINAP 100 96 59 (R)

6 (S)-tol-BINAP 50 40 80 (R)

[a] Reaction conditions: catalyst loading (5 mol %), H2 (25 bar), imine 17 (0.5 mmol), 1 mL

toluene, 24 hours; [b] conversion was determined by 1H NMR analysis; [c] % ee was

determined by GC; absolute configurations were assigned by comparison of retention times

and optical rotations with literature values.

In the next approach the modification of the Lewis acid was targeted. An effective way to

modify the Lewis acidity is grounded on the variation of the perfluorinated ring in the

catalyst. In 2009, Stephan and co-workers introduced the weaker Lewis acid B(p-C6F4H)3 and

applied it in catalytic reactions.[26]

In 2012, Mitzel and co-workers reported the synthesis of

bis(tetrafluorophenyl)borane HB(p-C6F4H)2 based on a transmetallation procedure of

HB(C6F5)2.[27]

Based on the previous reports the reaction of one equivalent HB(p-C6F4H)2

with the chiral alkene (1R,4R)-1,7,7-trimethyl-2-(2-naphthyl)-bicyclo[2.2.1]hept-2-ene 24 in

n-pentane afforded the chiral borane 25 in its pure diastereomeric form (1R, 2R, 3R, 4S). In

presence of t-Bu3P as Lewis base and one bar of H2 atmosphere the corresponding salt 26 was

formed in 53 % yield (Scheme 17).

19

Scheme 17. Synthetic pathway to chiral FLP 26.

The corresponding phosphonium hydrido borate 26 was fully characterized by multinuclear

NMR spectroscopy experiments. The19

F{1H}-NMR spectrum shows two sets of signals for

the diastereotopic C6F4 rings [δ = (ortho) -132.76 (m, 2F), (ortho) -133.31 (m, 2F), (meta) -

144.63 (m, 2F), (meta) -145.59 (m, 2F) ppm], whereas one set of signals was observed in 25

(Figure 4); 31

P-NMR spectrum δ = 59.0 (dm, JP-H = 432.96 Hz) ppm].

Figure 4. 19

F-NMR spectrum of compound 25 (bottom) compared with 19

F-NMR of compound 26 (top).

Slow crystallization of compound 26 from a mixture of dichloromethane and n-pentane

resulted in a crystal suitable for X-ray crystallographic analysis. The analysis showed FLP 26

in the expected (1R, 2R, 3R, 4S) configuration (Figure 5). In the solid state, the parallel

20

orientation of one of the fluorinated rings and the naphthyl moiety due to π-stacking, could be

one of the factors for high enantioselectivity in the hydrogenation reactions (Figure 5).[28]

Figure 5. Molecular structure of catalyst 26 in the crystal. Hydrogen atoms were omitted for clarity except for

the hydrogen atoms at para-position in perfluorophenyl ring and the hydrogens bound to boron and phosphorus.

Subsequently, the less Lewis acidic chiral catalyst 26 was tested in the asymmetric

hydrogenation of imines. Imine 17 and mono-substituted methoxy imine 20 were successfully

hydrogenated using 5 mol % of catalyst 26. 50 % and 80 % conversion were obtained within a

reaction time of 24 hours. Again, the methoxy substituted imine was hydrogenated faster, but

the stereoselectivity of the hydrogenation remained at 80 % and 81 % ee respectively (Table

4, entries 1 and 2). Based on this observations a further modification of the Lewis acid was

targeted.

In 2009, Rieger et al. showed that various TMS protected amines could activate H2 in

presence of B(C6F5)3 under mild reaction conditions.[29]

Moreover, the reactivity of TMS

protected phosphine t-Bu3PTMS with B(C6F5)3 generated t-Bu3PB(C6F4)B(C6F5)2.[29]

Based

on these results, we were able to achieve the synthesis of a new chiral phospholane

compound. TMS-protected phospholane (2.2 equiv.) was added slowly to 27 (1 equiv.) in n-

pentane, affording the corresponding chiral phospholane compound 28. In this transformation

the para-fluorine atom in the perfluorinated ring was replaced with the phospholane moiety

(Scheme 18). The new chiral compound 28 was characterized by NMR-spectroscopic

21

experiments. 19

F-NMR spectrum [δ = -128.96 (brs), -131.28 (brs) ppm] (Figure 6); 31

P-NMR

spectrum [δ = 4.00 (t, J = 31.2 Hz) ppm]; 11

B-NMR spectrum [δ = -16.3 (brs) ppm].

Scheme 18. Synthesis of chiral Lewis acid 28.

Figure 6. 19

F NMR spectrum of the new chiral catalyst 28 (bottom) compared with 19

F NMR of catalyst 27 (top)

In the subsequent reactions no H2 activation was observed using 28. For the enantioselective

hydrogenation of imines the catalytic use of 28 was tested. Again imine 17 and methoxy

substituted imine 20 were used as model substrates. At 65 °C, with 5 mol % loading of

catalyst 28 and after a reaction time of 24 hours, the enantioselective hydrogenation was

achieved with a conversion of 67 % for imine 17 and almost full conversion (95 %) for the

22

methoxy substituted imine 20. Enantiomeric excess using catalyst 28 was slightly better than

using 26 (83 % ee) (Table 4, entries 3 and 4).

Table 4. Enantioselective hydrogenation of imines using catalysts 26 and 28.

Entry[a]

Catalyst Substrate Conversion [%][b]

ee [%][c]

1 26 17 50 80 (R)

2 26 20 80 81 (R)

3 28 17 67 83 (R)

4

28 20 95 83 (R)

[a] Reaction conditions: catalyst loading (5.0 mol%), imine (0.5 mmol), H2 (25 bar), 1 mL

toluene, T = 65 °C, 24 hours; [b] Conversion was determined by 1H-NMR analysis; [c] %

ee determined by HPLC or GC methods using a chiral column; absolute configurations

were assigned by comparison of retention times and optical rotations with literature

values.

3.1.5 FLPs system with two Lewis acidic sites

In 1994 Marks and co-workers reported the first bifunctional Lewis acids incorporating C6F5

groups tBuCH2CH[B(C6F5)2]2.[30]

These bifunctional Lewis acids offer advantages over the

monofunctional boranes, as these compounds were considered less strong coordinating

reagents. For example these bifunctional Lewis acids as metallocene activators could enhance

the homogeneous olefin polymerization due to their weaker anion interaction.[30]

One year

later, Piers and co-workers reported the synthesis of similar compounds via dihydroboration

of the terminal alkynes using HB(C6F5)2 resulting in bifunctional Lewis acids.[25, 31]

Based on

this strategy several other chelating bifunctional perfluorinated Lewis acids [(C6F5)2B-linker-

B(C6F5)2] were synthesized and their properties were examined in catalytic olefin

polymerization (Figure 7).[32]

This year, Wegner and co-workers reported a new transition

metal-free bidentate system for the catalytic reduction of carbon dioxide. Carbon dioxide can

be selectively transformed to either methanol or methane depending on the reducing agent

used.[33]

23

Figure 7. Bifunctional Lewis acidic perfluorinated boranes.[32]

The first application of a bifunctional Lewis acidic compound in FLP methodology was

reported by Berke in 2009.[34]

The 1,8-bis(dipentafluorophenylboryl)naphthalene in presence

of a bulky Lewis base (2,2,6,6-tetramethylpiperidine) activated H2, affording the

corresponding zwitterionic compound. This Lewis acid forms a B-H-B bond with an angle of

121(3)° due to the proximity between the two borane centers (Scheme 19). Catalytic

hydrogenation of imines was successfully performed using this catalyst at 1.5 bar of H2 and a

reaction temperature of 120 °C.[34]

Scheme 19. Hydrogen activation by bifunctional Lewis acid[34]

In 2013, Du and co-workers investigated the asymmetric hydrogenation of imines by applying

bifunctional Lewis acidic compounds. The metal-free chiral borane catalysts were generated

via an in situ hydroboration of chiral diene during the asymmetric hydrogenation of imines

and high enantiomeric excess up to 89 % ee was achieved.[21]

One year later, Du and co-

workers reported a second application of these metal-free chiral dienes catalysts, the

enantioselective metal-free hydrogenation of silyl enol ethers to the corresponding alcohols.

Combining the established chiral dienes with B(C6F5)3 and t-Bu3P as Lewis base resulted in

high enantiomeric excess up to 99 % ee.[35]

Both reported Lewis acid systems were designed

in a way that the Lewis acidic centers are in close proximity.[21, 34]

FLP catalyst with two

24

Lewis acid sites seemed to influence the reactivity and the selectivity in asymmetric

transformations. Having the chiral monofunctional FLP catalysts (2, 3, 26 and 28) in hand, the

design of new chiral bifunctional Lewis acids with a large distance between the two Lewis

acid sites was planned.[32]

The synthetic strategy for the new camphor perfluorinated boron

compound was based on the synthesis routes for the established chiral FLP systems.[36]

The

lithiated alkene was generated by mixing 2.2 equivalent of t-BuLi at low temperature with

Cerium chloride and (1R)-(+)-camphor dissolved in THF to give the corresponding alcohol

29. Without further purification 29 was dehydrated using a mixture of thionyl chloride and

pyridine to give the corresponding 1,4-bis-camphor alkene compound 30. Hydroboration

using two equivalents of HB(C6F5)2 gave the desired perfluorinated boron compound 31

(Scheme 20). All possible diastereoisomers for compound 31 were avoided by heating the

reaction mixture up to 100 ºC. The thermodynamically favored diastereoisomer 31 was

selectively formed.

Scheme 20. Synthesis of chiral borane Lewis acid 31 and phosphonium hydrido borate zwitterion 32.

The corresponding bifunctional chiral borane Lewis acid 31 was fully characterized by

multinuclear NMR spectroscopy experiments. 19

F-NMR spectrum [δ = (ortho) -130.7 (m, 8F),

(para) -151.9 (m, 4F), (meta) -162.2 (m, 8F); ppm].11

B-NMR spectrum [δ = 41 ppm].

Interestingly, the 1H and

13C-NMR experiments show one signal at 6.87 (s, 4H) and 128.0 (s,

25

4C) ppm respectively, which corresponds to four hydrogen of the phenyl ring and reflects the

high symmetry of the compound. Single crystals of 31, suitable for X-ray structure

determination were grown from a hot n-pentane solution and the absolute configuration of 31

was determined as (1R, 2R, 3R, 4S) (Figure 8 - 31). It is important to note that so far no X-ray

analysis of the chiral Lewis acid could be obtained and only compound 31 enabled the

detailed analysis of the structure in the solid state.[19-20, 36]

Figure 8 shows the X-ray structure

of the novel chiral bifunctional Lewis acid 31 in comparison to the chiral FLP zwitterionic

compound 2. Similarly to the chiral compounds reported so far,[19]

the phenyl ring in the

chiral backbone of 31 is oriented parallel to one of the C6F5 rings in the two boron centers

(Figure 8). The average distance between the phenyl ring and the C6F5 group in each of the

two boron centers were measured and similar distance were observed (3.921 Å and 3.941 Å).

These findings are further in agreement with the high symmetry of compound 31. In addition,

the average distance between the phenyl ring and the C6F5 ring was measured and compared

to the zwitterionic compound 2. Shorter distance is observed in the zwitterionic compound 2

than for chiral borane 31, 3.657 Å and 3.921 Å respectively (Figure 8).

Figure 8. Crystal structure of 2 and 31, hydrogen atoms were omitted for clarity except for the hydrogen atoms

bound to boron. t-Butyl phosphonium cations in 2 were omitted and each red circle corresponds to the centroid

of the aromatic ring.

2 31

26

In presence of two equivalents of t-Bu3P and 1 bar of H2 pressure using n-pentane as solvent,

the two perfluorinated phenyl borane moieties of compound 31 reacted to give the

corresponding zwitterionic compound 32 (Scheme 20). Multinuclear NMR spectroscopy

experiments were performed, and are in agreement with the proposed structure for 32. 19

F-

NMR spectrum shows two sets of signals for the diastereotopic C6F5 rings [δ = (ortho) -

131.85 (m, 4F), (ortho) -132.00 (m, 2F), (para) -165.10 (t, J = 20.40 Hz, 2F), (para) -16.39 (t,

J = 20.30 Hz, 2F), (meta) - 167.93 (m, 8 F); ppm] (Figure 9). 31

P-NMR spectrum [δ = 59.52

(dm, JP-H = 443.8 Hz) ppm] and 31

P {1H}-NMR spectrum [δ = 59.52 ppm].

11B-NMR

spectrum [δ = -18.61 ppm]. In the 1H-NMR spectrum the aromatic region showed one signal

at 6.87 ppm, which corresponds to four hydrogen atoms in the aromatic ring of compound 31.

This information supports the similarity in the aromatic region between compound 31 and 32

and the highly symmetrical structure maintained after activation of molecular hydrogen.

Figure 9. 19


F-NMR of compound 32 (top)

Crystallization of compound 32 from a mixture of dichloromethane and n-pentane resulted in

crystals suitable for X-ray crystallographic analysis. Thus, the (1R, 2R, 3R, 4S) absolute

configuration of the activated phosphonium borate compound 32 was confirmed. Stacking

between the phenyl ring and the perfluorinated ring was observed. A comparison between the

27

X-ray structure of the non-activated bifunctional chiral Lewis acid 31 and the activated

phosphonium borate compound 32 shows no significant change in the distance between the

phenyl ring and the perfluorinated ring, 3.921 Å and 3.837 Å, respectively (Figure 10).

Figure 10. Crystal structure of compounds 31 and 32, hydrogen atoms were omitted for clarity except for the

hydrogen atoms bound to boron. Tri-tert-butyl phosphonium cations molecule in 32 were omitted and each red

circle corresponds to the centroid in the aromatic ring.

Based on the synthetic procedure for 31, the chiral borane Lewis acid compound 36 was

synthesized. The lithiated alkene was generated by Li-Br exchange in 33 using 2.2 equivalent

of t-BuLi at low temperature, and subsequent reaction with (1R)-(+)-camphor resulted in the

corresponding alcohol 34 (Scheme 21). Without further purification, 34 was dehydrated using

a mixture of thionyl chloride and pyridine to give the corresponding alkene 35. Hydroboration

using 2 equivalents of HB(C6F5)2 gave the desired compound 36.

31 32

28

Scheme 21. Synthesis of chiral borane Lewis acids 36 and 37.

The novel Lewis acid 36 was fully characterized by multinuclear NMR experiments. 19

F-

NMR spectrum [δ = (ortho) -130.7 (m, 8F), (para) -151.6 (m, 4F), (meta) -162.0 (m, 8F);

ppm]. 11

B-NMR spectrum [δ = 41.9 ppm] (Figure 11). The 1H-NMR and

13C-NMR spectrum

for 36 were comparable to 31, except for the central aromatic region, where three different

signals were obtained: 6.73 (s, 1H), 6.88 (d, JH-H = 7.43 Hz, 2H), 7.12 (t, JH-H = 7.43 Hz, 1H)

ppm in the 1H-NMR. From the

19F-NMR spectrum a compound with symmetric boron centers

can be concluded.

29

Figure 11. 19


F-NMR of compound 37 (top).

Single crystals of 36, suitable for X-ray structure determination were grown from hot n-

pentane solution and the absolute configuration of 36 was determined as (1R, 2R, 3R, 4S)

(Figure 12 - 36). In this Lewis acid the central aromatic ring is oriented parallel to the two

C6F5 rings and the distances between the centroids of the phenyl and the perfluorinated rings

in the boron center were measured at 4.94 Å (Figure 12). In comparison to the Lewis acid 31,

a much longer distance between the aromatic rings is visible and a different selectivity in

asymmetric transformations can be expected. The angles around the boron atoms in 31 and 36

are slightly different (Table 5).

Table 5. Comparison between selected angles in 31 and 36

Structure data (angle) 31 36

C23B1C8 / C7B1C13 115.2 ° 117.8 °

C17B1C23 / C1B1C13 123.8 ° 123.8 °

B1C8C7 / B1C13C12 113.3 ° 117.8 °

C8C7C1 / C13C14C23 117.3 ° 116.9 °

30

Figure 12. Comparing crystal structures of 31 and 36, hydrogen atoms were omitted for clarity, each red circle

corresponds to the centroid in the aromatic ring.

In presence of two equivalents of t-Bu3P and 1 bar of H2 pressure using n-pentane as solvent,

the two perfluorinated phenyl borane moieties of compound 36 reacted towards the

corresponding zwitterionic compound 37 (Scheme 21). Multinuclear NMR spectroscopy

experiments were performed, and are in agreement with the proposed structure of 37.

Selected peaks from 1H-NMR spectrum [δ = 5.10 (d, JP-H = 431.2 Hz, PH), 6.33 (s, 1H), 6.59

(m, 1H), 6.70 (m, 2H) ppm]. 19

F-NMR spectrum shows two sets of signals for the

diastereotopic C6F5 rings [δ = -131.59 (m, 4F), -131.97 (m, 4F), -166.54 (t, J = 20.26 Hz, 2F),

-167.49 (t, J = 20.30 Hz, 2F), -167.73 (m, 4 F), -167.91 (m, 4F) ppm]. 31

P-NMR spectrum [δ

= 59.36 (dm, JP-H = 432.2 Hz) ppm]. 31

P{1H}-NMR spectrum [δ = 59.36 ppm].

11B-NMR

spectrum [δ = -18.39 ppm]. In the 1H-NMR spectrum, the aromatic region is represented by

three separate signals at 6.33, 6.59 and 6.70 ppm and the 13

C-NMR spectrum showed four

different signals at 124.1, 125.1, 128.5, 129.4 which correspond to four carbon atoms in the

aromatic region. Comparing the NMR spectrum of 37 with the data obtained for the

corresponding compounds 31 and 32, a Lewis acid with comparable symmetry can be

proposed. The stacking between the phenyl-group and the perfluorinated rings and thus the

symmetry is maintained after the hydrogen activation, resulting in the corresponding

zwitterionic compounds (37).

31 36

31

After the synthesis of these bifunctional Lewis acids (31 and 36) and studying their behavior

according to the FLP methodology in the presence of 2 equivalents of t-Bu3P, a more detailed

study of the hydrogen activation with different Lewis bases was planned. In detail, the

possibility to selectively activate one Lewis acid-site should be investigated (Scheme 22).

Scheme 22. Selective activation of one Lewis acid-site in compound 31 and 36.

In a first attempt the reaction of 31 with one equivalent of Lewis base (t-Bu3P) in the presence

of H2 was targeted. However, the mono-activated Lewis acid could not be obtained and

instead a mixture of two compounds was identified. A similar behavior for compound 36 was

observed in the presence of one equivalent of t-Bu3P, and this result is largely based on the

similar Lewis acidity of the two boron centers. However, a new complex could be formed

using the bidentate Lewis base 1,2-bis(dimethylphosphino)ethane in anhydrous benzene

(Scheme 23). In the respective 31

P-NMR spectrum a selective reaction with a new signal at

9.46 ppm was observed. Based on this finding, the formation of symmetrical Lewis acid/base-

pair was concluded. However, in the 19

F-NMR spectrum ten separate signals were observed,

corresponding to independent C6F5-rings in the Lewis acid site [δ = -120.64 (m, 2F), -122.37

(m, 2F), -126.57 (m, 2F), -132.34 (m, 2F), -154.7 (m, 2F), -157.24 (m, 2F), -161.5 (m, 2F), -

162.34 (m, 2F), -162.84 (m, 2F), -164.38 (m, 2F); ppm]. This is also reflected in the 1H-NMR

spectrum, where two set of signals were detected from the aromatic bridging unit [δ = 7.6 (d,

JH-H = 7.87 Hz, 2H) and 7.2 (d, JH-H = 7.87 Hz, 2H); ppm]. Consequently, the interaction and

activation of the Lewis acid and Lewis base sites lead to the formation of the corresponding

compound 38, supporting the possibility of catalyst with two independent boron centers

(Scheme 23). However, in presence of hydrogen atmosphere, compound 38 did not activate

hydrogen due to the strong Lewis acid/base interaction.

32

Scheme 23. Lewis acid and Lewis base interaction of compound 31 with 1,2-bis(dimethylphosphino)ethane.

The corresponding reaction with 36 and one equivalent of t-Bu3P resulted in a mixture of

products. Addition of one equivalent of 1,2-bis(dimethylphosphino)ethane to compound 36 in

anhydrous dichloromethane showed a different outcome and the formation of a white

precipitate was observed. This precipitate could not be dissolved in polar solvents such as

dichloromethane, suggesting a polymerization reaction. This result confirms that the slight

structural change between 31 and 36 gives a significance different reactivity in presence of

bidentate Lewis base (1,2-bis(dimethylphosphino)ethane).

3.1.6 Application of the novel Lewis acid 31 and 36 in the asymmetric

hydrogenation of imines

The catalytic activity of 31 and 36 was investigated in the asymmetric hydrogenation reaction

of imines in the presence of chiral bidentate phosphines such as (R)- and (S)-tolyl binap

(Table 6). Hydrogenation of imine 17 using 5 mol % of 31 with (R)-tolyl binap gave full

conversion in 24 hours and the product was obtained in 66 % ee (Table 6, entry 1). Using (S)-

tolyl binap and the same reaction conditions, full conversion with identical enantioselectivity

was obtained (Table 6, entry 2). For methoxy substituted imine 22, using (R)- or (S)-tolyl

binap, resulted in 99 % conversions and 68 % ee (Table 6, entries 3 and 4). Obtaining the

same enantiomer of the product when either of the enantiomers of the Lewis base were used,

led to the conclusion that the chiral Lewis base does not influence the stereoselectivity of the

hydrogenation reaction (Table 6, entries 1-4). For the Lewis base t-Bu3P the hydrogenation of

naphthyl substituted imine 20 was investigated. Using 2 equivalents, 1 equivalent or no t-

Bu3P resulted in full conversion and 66 % ee were obtained (Table 6, entries 5, 6, and 7). The

amount of Lewis base thus has no effect on the enantiomeric excess obtained in the

33

hydrogenation. However, using catalyst 36 for the enantioselective hydrogenation of imine 17

and 21 in the presence of BINAP Lewis bases, gave full conversion and 78 % ee (Table 6,

entries 8-11). Moreover, no influence of the Lewis base was observed but the enantiomeric

excess obtained with 36 was high. In detail, 78 % ee was obtained using Lewis acid 37 instead

of 66 % ee using catalyst 31 (Table 6, entries 7 and 11). The higher enantiomeric excess

confirms the difference in reactivity of 31 and 36.

Based on the above results with respect to the catalytic experiments, no significant influence

of the Lewis base on the reactivity and enantioselectivity was observed. Consequently, the

enantioselective hydrogenation of various prochiral imines was performed using 5 mol % of

catalyst 36. Imines 18, 20, 21, 22 and 23 were hydrogenated with full conversion in 24 hours

and with high selectivity of 81 %, 79 %, 81 %, 74 % and 75% ee respectively (Table 6, entries

12-17).

Table 6. Enantioselective hydrogenation of imines using chiral Lewis acids FLPs 31 and 36.

Entry[a]

Substrate Lewis acid Lewis base Conversion [%][b]

ee [%][c]

1 17 31 (R)-tolyl BINAP >99 66 (R)

2 17 31 (S)-tolyl BINAP >99 66 (R)

3 22 31 (R)-tolyl BINAP >99 68 (+)

4 22 31 (S)-tolyl BINAP >99 68 (+)

5

20 31 t-Bu3P (2 equiv.) >99 66 (R)

6 20 31 t-Bu3P (1 equiv.) >99 67 (R)

7 20 31 - >99 66 (R)

8 17 36 (R)-tolyl BINAP >99 78 (R)

9 21 36 (S)-tolyl BINAP >99 78 (+)

10 21 36 t-Bu3P (2 equiv.) >99 78 (+)

11 21 36 t-Bu3P (1 equiv.) >99 78 (+)

12 17 36 - >99 78 (R)

13

18 36 - >99 81 (+)

14

20 36 - >99 79 (+)

15 21 36 - >99 81 (R)

16 22 36 - >99 74 (+)

17 23 36 - >99 75 (+)

[a] Reaction conditions: catalyst loading (5 mol %), imine (0.5 mmol), H2 (25 bar), 1 mL

toluene, T = 65 °C, 24 hours; [b] Conversion was determined by 1H NMR analysis; [c] % ee

34

determined by HPLC or GC methods using a chiral column; absolute configurations were

assigned by comparison of retention times and optical rotations with literature values.

It is clear, that the rate of the reaction is strongly dependent on the amount of catalyst used.

Therefore the rate of the hydrogenation reaction of imine 17 with Lewis acid catalysts (27)

and (31 or 36) was investigated. After 2 hours reaction time, 49 %, 64 % and 83 % conversion

and enantiomeric excess of 78 %, 79 % and 66 % ee was obtained, employing 27, 36 and 31

respectively (Table 7, entries 1, 2 and 3). Notably, the rate of the reaction using 31 is

considerably faster than with Lewis acid 36. Moreover, catalyst 31 gives within 2 hours twice

the yield in relation to 27, corroborating the effect of comparable structure. After 3 hours, 70

%, 85 % and 92 % conversion was obtained employing 27, 36 and 31 respectively (Table 7,

entries 4, 5 and 6). This difference in the rate and selectivity between 36 and 31 can be

attributed to the structural difference within these catalysts.

Table 7. Hydrogenation of imine 17 using catalysts 27, 31 and 36.

Entry[a]

Catalyst Time [h] Conversion [%][b]

ee [%][c]

1 27 2 49 78 (R)

2 31 2 83 66 (R)

3 36 2 64 79 (R)

4 27 3 70 78 (R)

5

31 3 92 67 (R)

6 36 3 85 78 (R)

[a] Reaction conditions: catalyst loading (10.0 mol%), imine (0.1 mmol), H2 (25 bar), 1 mL

toluene, T = 65 °C; [b] Conversion was determined by 1H NMR analysis; [c] % ee determined

by GC methods using a chiral column; absolute configuration was assigned by comparison of

retention time with literature values.

3.1.7 Conclusion

In summary novel chiral intramolecular FLPs were successfully synthesized and fully

characterized. Use of the stable catalysts at a low loading allowed the selective hydrogenation

of prochiral imines with an enantioselectivity up to 76 % ee. The new catalysts displayed an

increased recyclability in comparison to the related intermolecular system and the chirality in

the Lewis base did not show any influence on the enantioselectivity of the reaction.

35

Subsequent modification of the Lewis acidic site in the FLP enabled the development of the

Lewis acid 26 and 28 with increased selectivity in the hydrogenation of imines.

Based on a novel catalyst design the bifunctional Lewis acids 31 and 36 were synthesized and

fully characterized. The reactivity of 31 and 36 was studied in the presence of bidentate Lewis

base (1,2-bis(dimethylphosphino)ethane) and significant difference in reactivity between the

two compounds was observed.

36

3.1.8 Established synthetic procedure for the preparation of perfluroaryl

boranes

The application of strong Lewis acids in organic synthesis has initiated intensive research in

their preparation. Especially pentafluorophenyl substituted boranes were in the focus and

Chivers and coworkers enabled the synthesis of the respective pentafluorophenyl derivatives

in 1963.[37]

The strong Lewis acidic properties of this borane family moved these compounds

in the spotlights, as perfluorophenylboranes allowed many different applications.[38]

For

example tris(pentafluorophenyl)borane B(C6F5)3, first reported by Massey and Park in

1964,[39]

is an effective initiator for olefin polymerization reactions.[40]

The remarkable

properties of B(C6F5)3 spurred the development of new perfluoroaryl borane compound and

bis(pentafluorophenyl)borane HB(C6F5)2 was reported by Piers in 1995. This borane acts as a

strong hydroboration reagent for olefins,[25, 31]

vinyl silanes,[41]

allyl phosphines[14b]

and

transition metal metallocenes tethered to unsaturated functionalities with good regio- and

chemoselectivity.[42]

An analogue compound with the para-fluorine atoms were replaced by

hydrogen atoms, bis(tetrafluorophenyl)borane HB(p-C6F4H)2, was reported in 2012 by Mitzel

and co-workers.[27]

The preparation of HB(p-C6F4H)2 was based on the synthesis of

perfluoroaryl compounds via transmetallation reactions.[25, 31]

In 2006, Stephan and co-workers explored the reactivity of a molecule with a sterically

hindered Lewis acidic and basic site (C6H2Me3)2PH(C6F4)BH(C6F5)2, that allowed the

heterolytic cleavage of hydrogen affording the corresponding zwitterionic phosphonium

borate compound.[7]

Perfluorophenyl substituted boranes represent a cornerstone in FLP

catalysis and compound HB(C6F5)2 is one of the most used perfluorophenylborane sources

due to its ability to hydroborate alkenes and alkynes.[42b]

Until now perfluorophenyl

substituted boranes are the most common Lewis acids used for FLP activation of small

molecules and consequently represent a crucial part on the pathway to efficient metal-free

catalytic systems.[8a, 43]

In 2010 Chen et. al reported tailored chiral FLPs catalysts, based on the hydroboration of

(1R)-(+)-camphor derivatives using HB(C6F5)2 for enantioselective hydrogenation and

hydrosilylation of prochiral imines with an enantiomeric excess up to 87 % ee.[19-20, 36]

However, the complex synthesis of perfluorophenyl substituted boranes is still the laborious

experimental part, amplified by their sensitivity to oxygen and moisture. Hitherto,

perfluorophenyl substituted boranes are synthesized via transmetallation reactions of

C6F5SnMe2 with BCl3. The preparation of the Sn-compounds includes the synthesis of an

explosive organolithium intermediate LiC6F5. Subsequently, LiC6F5 is reacted with the highly

37

toxic and corrosive Me2SnCl2, resulting in Me2Sn(C6F5)2. Followed by another step with

explosion risk; reacting Me2Sn(C6F5)2 in anhydrous hexane up to 120 °C with BCl3 (b.p 12.6

°C) using thick-walled glass bomb for 96 hours. Purification of ClB(C6F5)2 is required to

completely remove traces of unreacted Me2SnCl2 by sublimation at 35 °C (Scheme 24).[31, 38]

Scheme 24. Established synthetic routes towards HB(C6F5)2.[31]

An alternative synthetic procedure has been reported, reacting B(C6F5)3 with Et3SiH in

benzene at 60 °C for 96 hours (Scheme 20).[44]

The main drawback of this route is the low

purity of the product.[31]

The preparation of the air sensitive HB(C6F5)2 is thus complicated

and often dangerous. Additionally, several analogous compounds with protected borane

groups were reported. In 2007 Hoshi et al. reported a more atom-economic synthesis of

bis(pentafluorophenyl)borane-dimethyl sulfide complex (C6F5)2HB.SMe2 as solution in

hexane by substituent redistribution between (C6F5)3B and BH3.SMe2. This reagent was used

for catalytic hydroboration of alk-1-yne with pinacolborane.[45]

In 2010 Lancaster and co-

workers reported a fast and convenient synthesis of the dimethyl sulphide adducts of mono-

and bis(pentaflurophenyl)borane from (C6F5)3B.OEt2.

[46] Later in 2011 Wagner and co-

workers disclosed a one-pot synthesis in 90 % yield. This reagent can be transformed in situ

to HB(C6F5)2 and used as a hydroboration agent for alk-1-ynes. This one-step synthesis

protocol is characterized by the use of two equivalents of C6F5MgBr and one equivalent of

BH3.SMe2, and subsequent reaction with one equivalent of Me3SiCl as hydride acceptor.

[47]

38

The reported research illustrates the importance of such effective pathways to novel Lewis

acids.

3.1.9 Novel synthesis pathways to the versatile Lewis acids HB(C6F5)2 and

HB(p-C6F4H)2

Herein the development of a new direct and simple two steps synthesis of HB(C6F5)2 and

HB(p-C6F4H)2, avoiding most of the limitations and disadvantages in the known synthetic

pathways, is presented. This novel procedure enables within two days the preparation of pure

crystalline HB(C6F5)2 on gram scale (Scheme 25).

Scheme 25. New synthetic pathway for HB(C6F5)2 and HB(p-C6F4H)2.

In detail, addition of C6F5MgBr to BF3.OEt2 in Et2O at 0 °C, and reaction at room temperature

for three hours gave (C6F5)2BF.OEt2. Bochmann and co-workers showed that heating

(C6F5)2BF.OEt2 results in fluoroethane release to give (C6F5)2B

.OEt.

[48] By avoiding extensive

heating by solvent removal at room temperature and at low pressure, pure (C6F5)2BF.OEt2 was

synthesized. Based on recent work by Stephan and co-workers,

(CH2Me3)2PH(C6F4)BF(C6F5)2 could react rapidly with dimethylchlorosilane (CH3)2SiHCl

giving (CH2Me3)2PH(C6F4)BH(C6F5)2 by selective F-H exchange.[7]

Consequently, by

dissolving the in situ generated crude (C6F5)2BF.OEt2 in (CH3)2SiHCl at 0 °C and allowing

the reaction to stir for 20 minutes at room temperature, results in the formation of a white

precipitate. Crystallization from anhydrous hot pentane gave HB(C6F5)2 in a 3 gram scale

with a 43 % yield (2 steps). Using similar reaction procedures, compound HB(p-C6F4H)2 was

synthesized starting from (p-C6F4H)MgBr with 45 % yield (2 steps). Suitable crystal for X-

ray crystallographic analysis obtained from recrystallization revealed HB(C6F5)2 as a dimer in

agreement with literature.[31]

39

Table 8. Comparison between established and novel synthetic pathway for HB(C6F5)2 and HB(p-C6F4H)2.[17]

Established synthetic pathway Novel synthetic pathway

Toxic starting materials Less toxic starting materials

Expensive starting materials Less expensive starting materials

Two steps with risk of explosion No risk of explosive steps

Two weeks preparation time Two days preparation time

3.1.10 Conclusion

In summary, the preparation and availability of a chemical is one of the most important

factors allowing it extensive use. Starting from cheap nontoxic materials, in fewer synthetic

steps, in a shorter preparation time and avoiding dangerous procedures enabled the synthesis

of Lewis acids HB(C6F5)2 and HB(p-C6F4H)2 (Table 8). This new improved synthetic

pathway will also facilitate synthesis of analogue Lewis acidic compounds.

40

3.2 Enantioselective Hydrosilylation and Hydroboration of Imines

3.2.1 Introduction

The reduction of imines to amines is an important transformation in organic chemistry[49]

and

the generation of chiral compounds by asymmetric reduction of imines represents a successful

strategy. A variety of metal complexes based on Rh,[50]

Ir,[51]

Ru,[52]

and Ti[53]

with phosphine

ligands have been used as catalysts for this asymmetric hydrogenation. The discovery of the

FLP methodology by Stephan and co-workers in 2006, where the tailored interaction between

Lewis acids and Lewis bases resulted in a novel reactivity paved the way for novel metal-free

reactions.[7]

In detail, asymmetric hydrogenation of prochiral imines using FLP catalyst could

be achieved with enantioselectivities up to 83 % ee.[19]

In addition the asymmetric

hydrosilylation of imines was reported and enantioselectivities up to 87 % ee were

obtained.[20]

As early as 2000, Piers and co-workers reported the hydrosilylation of imines using B(C6F5)3

by activation the Si-H bond.[54]

Mechanistic investigations were performed and abstraction of

a hydride from silane by B(C6F5)3 in presence of imine substrate lead to the formation of

silyliminium/hydridoborate ion pair. Subsequent hydride attack generated the desired product

and B(C6F5)3 (Scheme 26).[54]

Later in 2010, Alcarazo and co-workers extended the silane

activation concept according to FLP methodology by incorporating

hexaphenylcarbodiphosphorane and B(C6F5)3. The ensemble heterolytically cleaved the Si-H

bond resulting in the corresponding zwitterionic compound.[55]

41

Scheme 26. Proposed mechanism for hydrosilylation of imines using B(C6F5)3.

As discussed earlier no effect of the Lewis base was noticed on the enantiomeric excess

obtained during the asymmetric hydrogenation of imines. In contrast to this, the choice of the

Lewis base used for hydrosilylation is important. In the absence of catalytic amounts of Lewis

base and in presence of chiral Lewis acid 27, full conversion was obtained within 2 hours with

only 2 % ee (Table 9, entry 1). Combining 27 with Mes3P as Lewis base, the rate of reaction

decreased (67 % conversion after 4 days) and enantiomeric excess increased to 63 % ee

(Table 9, entry 2). Replacing Mes3P with more basic t-Bu3P resulted in 55 % conversion,

albeit higher enantiomeric excess of 79 % ee was obtained (Table 9, entry 3).[20]

42

Table 9. Effect of Lewis base modification in asymmetric hydrosilylation.[20]

Entry[a]

Catalyst Time

Conversion [%][b]

ee [%][c]

1 27 2h >99 <2 (R)

2 27/Mes3P 4d 67 63 (R)

3 27/t-Bu3P 4d 55 79 (R)

[a] Reaction conditions: catalyst loading (5 mol %), imine 17 (0.5 mmol), PhMe2SiH (0.55

mmol), T = r.t, 1 mL toluene; [b] Conversion was determined by 1H-NMR analysis; [c] % ee

was determined by GC; absolute configuration was assigned by comparison of retention time

and optical rotation with literature values.

These three single experiments already give a clear indication of the importance of Lewis acid

and Lewis base interplay in the asymmetric hydrosilylation. While the effect is of minor

importance in the asymmetric hydrogenation, an enhanced effect can be observed in reactions

with silanes and boranes. Consequently, the combination of Lewis acid and Lewis base have

to be tailored with respect to activity, but more importantly on the influence on

enantioselectivity. Currently the effect of the different combinations is rather unclear and has

to be enlightened to pave the way to effective FLP catalyst for further asymmetric

transformations. In detail, due to the significant influence of the Lewis base used in the

asymmetric hydrosilylation, it would be also important to study the influence of modifying

the chiral Lewis acid. The modifications in the chiral Lewis acid/base catalysts were

structured, so that altering the structure and the acidity strength on the catalyst performance

can be investigated in detail.

43

3.2.2 Enantioselective Hydrosilylation of imines using FLPs catalysts

The catalytic activity of the structurally diverse chiral FLPs catalysts (Figure 13) was

systemically tested for the asymmetric hydrosilylation of imines. In a glove box a reaction

vial with stirring bar was charged with imine (0.5 mmol, 1.0 equiv.), 5 mol % catalyst and

anhydrous toluene (1 mL). Dimethylphenylsilane (0.55 mmol, 1.1 equiv.) was added to the

solution and the reaction mixture was stirred for the indicated period of time in the glove box

at room temperature. The conversion of the substrate was determined by 1H-NMR

spectroscopy of the crude reaction mixture.

Figure 13. Chiral FLP catalysts tested in hydrosilylation of imines.

The results of the catalytic experiments with the different Lewis acids are presented in table

10. In presence of catalyst 2 after 96 hours, 50 % conversion and 83 % ee was obtained (Table

10, entry 1). Replacing the phenyl ring in catalyst 2 by a bulkier substituent (naphthyl group)

in catalyst 3, 61 % conversion and a slight increase in enantioselectivity 84 % ee was noticed

(Table 10, entry 2). In the presence of the intramolecular FLP catalyst 16, 61 % conversion

and lower enantioselectivity of 47 % ee was obtained (Table 10, entry 3). Moreover, these

findings could be a result of the weaker Lewis base in catalyst 16 in comparison to t-Bu3P in

catalyst 2. Moreover, these results verify the importance of the aromatic group in the FLP

catalyst, considered as lead structures for the metal-free catalyst used in the enantioselective

hydrosilylation of imines. After studying the aromatic region in the catalyst, the effect

variation on the perfluorinated boron part was targeted. By replacing the para-fluorine with a

hydrogen atom, the less Lewis acidic catalyst 26 was obtained. In the respective reaction the

44

rate slightly increased and after the same reaction time, 70 % conversion with a lower

selectivity of 60 % ee was obtained (Table 10, entry 4). Combining the positive properties of

the catalysts 2 and 3, catalyst 28 with the phospholane moiety was synthesized. Under the

same reaction conditions, the highest enantioselectivity of 88 % ee was obtained using this

catalyst (Table 10, entry 5). Consequently, the effect of bifunctional Lewis acids 31 and 36 in

the asymmetric hydrosilylation reaction was investigated. In presence of the bifunctional

Lewis acid catalysts 31 in combination with 2 equivalents of t-Bu3P, after 48 hours, 82 %

conversion and 65 % ee was obtained. In presence of 36 and two equivalents of t-Bu3P, an

enantioselectivity of 77 % ee could be obtained at 40 % conversion (Table 10, entries 6-7).

Similarly to the enantioselective hydrogenation of prochiral imines, both catalysts 31 and 36

showed a clear difference in reactivity and selectivity for the enantioselective hydrosilylation

of imines. The rate of the hydrosilylation reaction in presence of 31 is almost double than that

of 36, whereas the enantiomeric excess obtained using 36 is higher than the one obtained

using 31. This can be attributed to structural difference between both bifunctional Lewis acids

31 and 36.

Table 10. Enantioselective hydrosilylation of imine 5 using chiral FLPs 2, 3, 16, 26, 28, 31 and 36.

Entry[a]

Catalyst Conversion [%][c]

ee [%][d]

1 2 50 83 (R)

2 3 61 84 (R)

3 16 61 47 (R)

4 26 70 60 (R)

5 28/t-Bu3P (1 equiv.) 55 88 (R)

6[b]

31/t-Bu3P (2 equiv.) 82 65 (R)

7[b]

36/t-Bu3P (2 equiv.) 40 77 (R)

[a] Reaction conditions: catalyst loading (5.0 mol%), imine (0.5 mmol), PhMe2SiH (1.1

equiv.), 1 mL toluene, T = r.t, 96 hours; [b] Reaction time 48 hours; [c] Conversion was

determined by 1H-NMR analysis; [d] % ee determined by GC methods using a chiral column;

absolute configuration was assigned by comparison of retention time and optical rotation with

literature values.

45

3.2.3 Metal-catalyzed asymmetric hydroboration

The catalytic hydroboration reaction provides access to functionalized organoboron

derivatives that cannot be easily prepared using traditional approaches. For example the direct

catalytic addition of ammonia or amine to alkenes is a challenging step. However, this goal

can be achieved by a two-step reaction in which catalytic asymmetric hydroboration is

followed by an amination step.[56]

Transition-metal catalysts offer various advantages in the

asymmetric hydroboration reactions and the asymmetry can be introduced via chiral ligands

on the metal catalyst or within the substrate.[56-57]

Recently, Rhodium catalyzed hydroboration

of olefins using Pinacol borane (HBPin) was dramatically improved by the addition of the

Lewis acid co-catalysts (B(C6F5)3).[58]

The proposed mechanism included the indirect transfer

of HBPin to the catalyst via heterolytic cleveage of the B-H bond to produce [HB(C6F5)3-] and

[PinB-THF+]. Followed by hydride transfer from [HB(C6F5)3

-] affords a neutral Rh(I) hydride

species which then undergoes oxidative addition of the borenium THF species to yield a

cationic Rh(III) complex. Then the substrate (E)-4-octene, coordinates and hydroboration of

the olefin proceeds to generate the hydroborated product (Scheme 27).[58]

46

Scheme 27. Proposed mechanism for B(C6F5)3 promoted hydroboration catalysed by molecular Rh-catalyst[58]

In 2008 Stephan and co-workers reported the activation of the B-H bond of catechol borane

(HBCat) by the combined use of B(C6F5)3 and t-Bu3P to give the corresponding product

[(C6H4O2)BPtBu3][HB(C6F5)]3, described as either borenium cation or boryl-phosphonium

salt (Scheme 28a).[59]

Later, Crudden and co-workers showed, that the B-H bond of HBPin

can be heterolytically cleaved in the presence of B(C6F5)3 and DABCO, resulting in the

formation of the corresponding product [(C6H14O2)BDABCO][HB(C6F5)]3 (Scheme 28b).[60]

Scheme 28. Selected examples of borenium ion generation according to FLP methodology

47

Catalytic reduction of imines was successful using this novel metal-free Lewis acid/Lewis

base pairs.[60]

Later, a mechanistic investigation on the reaction was performed and borenium-

catalyzed imine hydroboration via [DABCO-BPin]+ [B(C6F5)4

-] or [DABCO-BPin]

+

[HB(C6F5)3-] was postulated. The rate difference of the reaction between the two catalytic

systems supported the catalytic system [DABCO-BPin+] [B(C6F5)4

-]. Based on this result the

proposed mechanism proceeds via the transfer of borenium ion in [DABCO-BPin+] to imine.

The obtained boron-activated iminium ion is then reduced by HBPin in presence of DABCO

to yield the hydroborated imine. However, B(C6F5)3 is not involved in the catalytic cycle and

acts only as an initiator for the system (Scheme 29).[60]

Scheme 29. Proposed mechanism of borenium-catalyzed imine hydroboration[60]

3.2.4 Enantioselective hydroboration of imines in presence of chiral boranes

Based on the recent findings the application of FLPs for enantioselective hydroboration of

imines should be developed. For our studies imine 17 was used as a model substrate together

with Lewis acid 27. In a first set of experiments, 17 could be hydroborated using 5 mol % of

enantiopure chiral borane 27 and the addition of PinBH (1.1 equiv.) at room temperature. In

this reaction 47 % conversion and only 8 % ee were obtained (Table 11, entry 1). With the

usage of DABCO, the rate of the reaction increased (62 % conversion) and enantioselectivity

of 38 % ee could be achieved (Table 11, entry 2). Using Ph3P instead of DABCO gave the

same conversion and enantiomeric excess (Table 11, entry 3). Replacing Ph3P with Mes3P

resulted in 48 % conversion and a lower enantiomeric excess of 26 % ee (Table 11, entry 4).

The reaction using chiral borane 27 in combination with t-Bu3P reduced the rate (21 % of the

48

corresponding product), but 60 % enantioselectivity could be obtained (Table 11, entry 5).

Subsequently the influence of the solvent was targeted and toluene was replaced

trifluoromethybenzene (PhCF3). In presence of DABCO as Lewis base the rate of the reaction

increased dramatically and full conversion of 17 to the corresponding amine was obtained

within 5 hours. However, the enantioselectivity decreased to 10 % ee (Table 11, entry 6). In

presence of t-Bu3P as Lewis base and in PhCF3 or bromobenzene (PhBr) the rate of the

reaction decreased and selectivity of 24 % ee was obtained (Table 11, entries 7 and 8).

Consequently, the best reaction conditions with respect to enantioselectivity were in the low

polar solvent toluene and with t-Bu3P as a Lewis base.

Table 11. Lewis base and solvent effect on hydroboration of imine 17 using chiral Lewis acid

catalyst 27.

Entry[a]

Catalyst[LA/LB] Solvent Conversion [%][b]

ee [%][c]

1 27/- toluene 47 8 (R)

2 27/DABCO toluene 69 38 (R)

3 27/Ph3P toluene 47 26 (R)

4 27/Mes3P toluene 48 26 (R)

5 27/t-Bu3P toluene 21 60 (R)

6[d]

27/DABCO PhCF3 >99 10 (R)

7 27/t-Bu3P PhCF3 32 24 (R)

8 27/t-Bu3P PhBr 32 24 (R)

[a] Reactions conditions: catalyst (5 mol %), imine (0.25 mmol), PinBH (0.28 mmol), T = r.t,

24 hours; [b] Conversion was determined by 1H-NMR analysis; [c] % ee determined by GC

method using chiral column; absolute configuration assigned by comparison of retention time

and optical rotation with literature values; [d] Reaction time: 5 hours.

49

3.2.5 Mechanistic investigation on the enantioselective hydroboration with

chiral FLP catalysts

The mechanistic investigations were initiated by monitoring the reaction process via NMR

experiments using imine 17 as model substrate. In the absence of FLP catalyst, hydroboration

of imine 17 was successful with 1.1 equivalent of CatBH. In the NMR experiment a mixture

of starting imine 17, amine 39, enamine 40b and hydroborated product 41b were obtained

after 8 hours (Table 12, entry 1). Replacing CatBH with PinBH in the absence of FLP catalyst

no hydroboration of imine 17 was observed (Table 12, entry 1).

In order to obtain more detailed information, the chiral FLP catalyst (27 and tBu3P, 5 mol %)

and imine 17 were combined in anhydrous deuterated toluene with PinBH or CatBH (Table

12). After 5 minutes reaction time, 56 % of the product 41b could be determined together

with 15 % enamine 40b and 10 % amine 39 (Table 12, entry 2). The corresponding reaction

with PinBH gave only very low conversion (Table 12, entry 2). After 30 minutes the reaction

with CatBH was nearly completed and 83 % of the product 41a was obtained (Table 12, entry

3). After this time also PinBH showed conversion and 20 % 41a could be detected via NMR.

Within a reaction time of 1 hour the transformation with CatBH was completed and 88 %

yield of 41b and 12 % 40b could be obtained (Table 12, entry 4). In this asymmetric reaction

a high selectivity of 78 % ee could be observed (Table 12, entry 5). The same hydroboration

reaction with PinBH was performed and after 24 hours 38 % of 41a, 25 % of 40a together

with 28 % amine 39 were determined (Table 12, entry 5). In this transformation the selectivity

is slightly lower and only 60 % ee were measured (Table 12, entry 5). In summary, the rate of

the reaction was higher when CatBH was used as hydroboration reagent in comparison to

PinBH. The difference in rate can be explained by the weaker B-H bond in CatBH, rendering

the borane more active.[61]

N-boronated enamine and amine formation were clearly observed

in the case of PinBH and formed during the reaction in equimolar ratio. However, the

formation of enamine 40b and amine 39 side products propose novel pathways, which were

not reported before for the hydroboration of imines.

In 2013, Oestreich et al. reported a refined mechanistic investigation of the hydrosilylation of

imines detecting novel N-silylated enamine and amine intermediates.[62]

Si-H bond activation

based on the FLP principle tends to generate a silyliminium ion and a borohydride. The

hydrosilylation reaction proceeded via the initial formation of N-silylated amine, followed by

the hydride transfer from the borohydride anion.[62]

Detailed experiments were performed and

the corresponding enamine and amine formed during the experiment disappeared after longer

50

reaction time.[62]

However, in the present hydroboration reaction the enamine formed during

the reaction did not disappear after a prolonged reaction time of 72 hours, whereas the amine

39 completely faded with CatBH (Table 12, entry 6).

Table 12. Comparison of hydroboration of imine 17 with PinBH and CatBH and FLP 27/t-Bu3P

Entry[a]

R.t. RB-H 17[%][b]

39[%][b]

40a,b [%][b]

41a,b [%][b]

ee[%][c]

1[d]

8 hrs. CatBH

PinBH

17

100

4

0

2

0

77

0

-

2 5 min. CatBH

PinBH

18

94

10

3

15

2

56

1

-

3 30 min. CatBH

PinBH

0

47

2

17

15

16

83

20

-

4 1 hr. CatBH

PinBH

0

38

0

19

12

22

88

20

-

5 24 hrs CatBH

PinBH

0

9

0

28

12

25

88

38

78

60

6 72 hrs CatBH

PinBH

0

7

0

22

12

21

88

50

-

[a] Reaction conditions: catalyst (5 mol %), imine (0.5 mmol), PinBH or CatBH (0.54 mmol),

deuterated benzene (C6D6), T = r.t.; [b] Conversion was determined by 1H-NMR analysis;

[c] % ee determined by GC method by using a chiral column, absolute configurations

assigned by comparison of retention time and optical rotation with literature values; [d] no

FLP catalyst.

51

The equimolar amounts of enamine 40a and amine 39 revealed that the imine is acting as

Lewis base to generate an enamine.[62]

The non-equimolar amounts of the enamine 40b and

amine 39 formed in case of CatBH after prolonged reaction time, indicated that also t-Bu3P

can generate the enamine side product. Consequently, the same reaction conditions were

applied, but now in the absence of t-Bu3P. The rate of the reaction was slightly increased and

after 5 minutes no imine could be observed. After 1 hour 40b was the major product and

equimolar amounts of enamine 40b and amine 39 were detected (Table 13, entries 1 and 2).

The equimolar amounts of enamine 40b and amine 39 in the absence of t-Bu3P (Table 13,

entry 3) explain the unexpected enamine 40b as a side product with t-Bu3P. Using four

equivalents of t-Bu3P as a Lewis base, resulted in a slow reaction rate (Table 13, entry 4). The

selectivity of the reaction decreased dramatically from 38 % to 15 %. This dramatic decrease

in the selectivity could be based on the blocking of the chiral boron hydride by the excess of

Lewis base t-Bu3P and the desired product 41b is instead formed via the direct hydroboration

of imine 17 by CatBH.

Table 13. Hydroboration using CatBH with varying amounts of Lewis base t-Bu3P.

Entry[a]

Reaction time 17[%][b]

39[%][b]

40b[%][b]

41b[%][b]

%ee[c]

1 5 min. 0 14 11 75 -

2 1 hr. 0 11 8 81 -

3 24 hrs. 0 2 0 98 38

4[d]

1 hr. 22 0 7 71 15

[a] Reaction conditions: catalyst 27 (5 mol %), imine (0.5 mmol), CatBH (0.54 mmol),

deuterated benzene (C6D6), T = r.t.; [b] Yield was determined by 1H-NMR analysis; [c] % ee

determined by GC method using chiral column; absolute configurations assigned by

comparison of retention time and optical rotation with literature values; [d] Excess of t-Bu3P

(4 equiv.) was added.

52

3.2.6 Proposed mechanism for enantioselective hydroboration of imines using

Frustrated Lewis Pair

Based on the previous findings for the activation of boranes with FLP catalysts [59-60]

and our

new experimental discoveries (Table 13), a mechanism for the hydroboration of imines using

the FLP catalyst and CatBH has been developed. The mechanistic experiments showed the

existence of two common reaction pathways and the general mechanistic picture is depicted in

Scheme 30. The first pathway A is the direct hydroboration of the imine substrate with CatBH

without FLP catalyst, affording the amine product 41b as a racemic mixture. The second

faster reaction pathway B involves the FLP catalyst and enables the asymmetric

transformation. In the initial step the B-H bond in CatBH is heterolytically cleaved by the

chiral boron Lewis acid in presence of t-Bu3P as Lewis base, generating the borenium

phosphonium ion intermediate 42. Then, the borenium ion in 42 is transferred to imine 17,

resulting in the corresponding iminium ion pair compound 43. Hydride transfer from the

borate is the critical step to close the catalytic cycle and to release amine via 41b in enantio-

enriched form.

In the NMR experiments the additional formation of enamine side product 40b was depicted.

As a result of the proton abstraction from the borenium ion 43 by imine 17 or t-Bu3P, the

respective formation of iminium 44 or phosphonium borohydride compound 45 could be

detected. The observation of this iminium borohydride compound leads to a second minor

pathway for the formation of amine 39, using compound 44 as hydroboration reagent.

53

Scheme 30. Two reactions pathways for the hydroboration of imine 17 using CatBH as a hydroborating reagent.

In the absence of the Lewis base t-Bu3P an additional mechanistic scenario is proposed based

on the comprehensive NMR investigations. In detail, the appearance of equimolar amounts of

enamine 40b and amine 39 in the initial reaction phase (Table 13, entries 1 and 2), and their

fading after longer reaction time (Table 13, entry 3) is elucidated in the mechanistic picture

shown in scheme 31. The boron Lewis acid and amine product 39 should react with CatBH to

the iminium borohydride ion pair 46. Subsequently, the formed enamine 40b will be

protonated by 46 to reform the borenium ions 43, finally resulting in amine product 41b.

To further support the proposed mechanism, additional experiments were performed. Using 2

equivalents of CatBH and the imine substrate, the selectivity of the reaction slightly dropped

from 78 % ee to 72 % ee. In addition to that, increasing the catalyst loading from 5 mol % to

10 mol % increased the selectivity marginally from 78 % ee to 81 % ee. All these results

support and confirm the proposed reaction pathways for the hydroboration of imines using

CatBH as a hydroborating reagent.

54

Scheme 31. Additional mechanistic scenario in the hydroboration of imines with FLPs.

3.2.7 Enantioselective hydroboration of imine 17 in presence of selected chiral

FLPs catalysts

Having different chiral Lewis acids synthesized, the influence of the Lewis acid modification

in the hydroboration of imines was investigated in more detail. Using 5 mol % of

intramolecular FLP catalyst 16, 96 % conversion gave a 93/3 amine/enamine ratio and low

enantiomeric excess of 6 % ee for the amine (major product). This result could be based on

the weaker Lewis base in catalyst 16 in comparison to t-Bu3P (Table 14, entry 1), in

agreement to the results with different Lewis bases. The less Lewis acidic catalyst 26 enabled

full conversion with a 90/10 amine/enamine ratio and 50 % ee (Table 14, entry 2). Using

chiral phospholane catalyst 28, 100 % conversion and 83/17 amine/enamine ratio with 54 %

ee was obtained (Table 14, entry 3). In presence of the bifunctional Lewis acid catalysts

systems 31 and 37, after 12 hours full conversion and a amine/enamine ratio of (78/22) and

(76/24) was obtained with 73 % ee and 80 % ee respectively (Table 14, entries 4 and 5).

55

Table 14. Enantioselective hydroboration of imines using chiral FLPs catalysts 16, 26, 28, 31 and 36

Entry[a]

Catalyst Conversion: Amine/Enamine

[%][b] ee [%]

[c]

1 16 96:93/3 6 (R)

2 26 100:90/10 50 (R)

3 28/t-Bu3P 100:83/17 54 (R)

4[d]

31/t-Bu3P 100:78/22 73 (R)

5[d]

36/t-Bu3P 100:76/24 80 (R)

[a] Reaction conditions: catalyst (5 mol %), imine (0.5 mmol), CatBH (0.54 mmol),

deuterated benzene (C6D6), T= r.t., 24 hours. [b] Yield was determined by 1H-NMR anaylsis.

[c] % ee determined by GC method using chiral column; absolute configurations assigned by

comparison of retention times and optical rotations with literature values. [d] Reaction time =

12 hours.

3.2.8 Enantioselective hydroboration of selected imines using chiral catalyst 3

Based on the developed mechanistic picture the optimized reaction conditions were identified.

In detail, t-Bu3P as Lewis base, CatBH as hydroborating reagent and chiral catalyst 3, showed

the highest selectivity and conversion for the hydroboration of imine 17. Consequently,

various other acyclic N-aryl imines with chiral FLP catalyst 3 were screened. All reactions

were performed at room temperature with 5 mol % catalyst loading of 3 and CatBH (1.1

equiv.) in deuterated benzene as solvent for 24 hours.

With imine 17 full conversion and an 88/12 amine/enamine ratio at 78 % ee was obtained

(Table 15, entry 1). Replacing the phenyl group with 2-napthyl imine 18, 84 % of the

corresponding amine and 15 % enamine were formed with 80 % enantioselectivity (Table 15,

entry 2). Imine 19 with electron withdrawing chlorine substituent at the para-position gave

90/10 amine/enamine ratio and 70 % ee (Table 15, entry 3). Methoxy substituted imines 20,

21 and 22 gave 85/15, 88/12 and 89/11 amine/enamine ratio with 80 % ee (Table 15, entries

4, 5, 6). In addition to that, methoxy and chloro substituted imine 23 gave full conversion and

92/8 amine/enamine percentage ratio with 76 % ee (Table 15, entry 7).

56

Table 15. Hydroboration of imines using chiral catalyst 3.

Entry[a]

Substrate Conversion: Amine/Enamine

[%][b]

ee [%][b]

1 17 100:88/12 78 (R)

2 18 84:69/15 80 (-)

3 19 100:90/10 70 (-)

4 20 84:69/15 80 (R)

5 21 90:81/9 80 (+)

6 22 100:89/11 80 (+)

7 23 100:92/8 76 (+)

[a] Reaction conditions: catalyst (5 mol %), imine (0.5 mmol), CatBH (0.54 mmol),

deuterated benzene (C6D6), T= r.t., 24 hours. [b] Yield was determined by 1H-NMR anaylsis.

[c] % ee determined by GC method using chiral column; absolute configurations assigned by

comparison of retention times and optical rotations with literature values.

3.2.9 Conclusion

In conclusion, the asymmetric metal-free catalytic hydrosilylation and hydroboration of

different substituted imines using chiral FLPs methodology was developed, affording the

amine product with high enantioselectivities. The influence of the chiral Lewis acid and the

choice of Lewis base was studied for both reactions. Both the Lewis acid and Lewis base used

have a dramatic effect on the rate of the reaction and the selectivity obtained for both

reactions (hydrosilylation and hydroboration). Chiral phospholane catalyst 28 in combination

with t-Bu3P as a Lewis base resulted in the highest enantiomeric excess for the hydrosilylation

reaction up to 88 % ee, whereas catalyst 3 was the best catalyst for the enantioselective

hydroboration reaction and up to 80 % ee was obtained. Novel amine and N-boronated

enamine formation in hydroboration reaction of imines were detected using FLPs catalysts.

The choice of the hydroborating reagent had a crucial role in terms of the reaction rate,

reaction pathway and so the enantioselectivity obtained. CatBH showed better results than

PinBH with respect to conversion, rate and selectivity. PinBH favored the formation of the

novel enamine side product, in which the rate of the reaction and selectivity were low

57

compared to the case of CatBH. Moreover, in case of using CatBH as a hydroborating

reagent, two reaction pathways were possible (Pathway A and B). The use of t-Bu3P as a

Lewis base is the key element to shift the reaction from pathway A to pathway B and so the

enantioselective reaction pathway according to FLP methodology will take place with high

enantiomeric excess up to 80 % ee.

58

4. Conclusion

The frustrated Lewis pair methodology is based on the tailored interplay of a Lewis acid with

a Lewis base. The modification of the electronic properties and the steric environment of both

partners are the basic design principals and vital parameters to avoid the Lewis acid/base

adduct formation.

In this thesis novel FLP catalysts derived from (1R)-(+)-camphor (4) were synthesized and

tailored for the application in asymmetric hydrogenation, hydrosilylation and hydroboration

reactions (Scheme 32).

Scheme 32. Selective chiral FLP catalysts

The reactivity of these catalysts was tested in different asymmetric transformations, with a

special focus on the role of both FLP partners in the activation of the respective reagents and

the enantioselectivity. In the asymmetric hydrogenation, the Lewis base had minor influence

on the enantiomeric excess obtained in the transformation and enantioselectivity up to 83 %

ee could be obtained. Moreover, the developed chiral intramolecular FLP catalyst 16 showed

a significant increase in stability and enabled efficient catalyst recycling. However, in the

59

asymmetric hydrosilylation and hydroboration, the Lewis base has a vital effect on the rate of

the reaction and the enantiomeric excess obtained. Consequently, combinations with different

Lewis bases were tested and the best enantioselectivity was obtained using t-Bu3P in

combination with the chiral Lewis acid (Scheme 33; b and c). Further modifications in the

perfluorinated ring of the Lewis acid catalyst showed a significant influence on reactivity and

enantioselectivity, resulting in the phospholane derived chiral catalyst 28 with an

enantiomeric excess of 88 % ee in the asymmetric hydrosilylation of imines. In the

hydroboration reaction compounds 3 and 36 could be established as effective catalysts,

resulting in an enantioselectivity up to 80 % ee. Based on detailed mechanistic investigations

the influence of the two FLP components in the enantioselective hydroboration was

investigated, resulting in a detailed reaction mechanism and guiding principles for the

development of new catalyst systems for this transformation.

Scheme 33. Enantioselective hydrogenation, hydrosilylation and hydroboration using chiral FLPs catalysts.

60

Furthermore, new bifunctional perfluorinated borane compounds 31 and 36 were synthesized

and fully characterized. The different arrangement of the two Lewis acids in these compounds

(31 and 36) showed a profound influence on reactivity or enantioselectivity, and catalysts 36

could be established as novel effective catalysts system, paving the way for future FLP

catalyst development. As perfluorinated boranes represent the critical part in FLPs chemistry,

a new synthetic pathway for the important hydroborating reagents, HB(C6F5)2 and HB(p-

C6F4H)2 could developed, facilitating in the future the synthesis of novel metal-free catalysts.

.

61

5. Experimental part:

5.1 General

All reactions involving air or moisture-sensitive compounds were carried out under argon

using standard Schlenk techniques or inside a glove box. Solvents for extraction and

chromatography were technical grade and distilled prior to use. Solvents used in reactions

were dried and distilled prior to use. Unless otherwise noted, all materials were obtained from

commercial suppliers were used without further purification. NMR experiments were

performed on a Bruker AV-300, AV-400 or AV-600 spectrometer. 1H and

13C-NMR spectra

were referenced to SiMe4 or the residual solvent peak. 31

P, 11

B, and 19

F-NMR spectra were

referenced externally to 85 % H3PO4, BF3·Et2O and CF3CO2H. Chemical shifts were given in

ppm and spin-spin coupling constants, J in Hz. For the description of multiplicity of the signal

following abbreviations were used: s = singlet, d= doublet, t = triplet, m = multiplet, br =

broad. Compounds 16, 26, 31, 32 and 36 were studied by single crystal X-ray diffraction. For

intensity data collection the crystals were mounted on glass fibers and placed directly in a

cold stream of dinitrogen (T = 130 K). Intensity data were collected with a Bruker Smart

APEX CCD (Mo-K radiation, = 0.71073 Å, graphite monochromator) area detector on a D8

goniometer in the ω scan mode. A temperature of 130(2) K was maintained for all data

collections with the help of an Oxford Cryosystems Cryostream 800 cooler. Multi-scan

absorption corrections were performed by SADABS.[63]

The structures were solved by direct

methods (SHELXS97) and refined by full matrix least-squares on F2 (SHELXL97).[64]

Non-

hydrogen atoms were assigned by anisotropic displacement parameters (except the disordered

parts), and H atoms were introduced in their idealized positions and refined using a riding

model. The absolute configurations were confirmed by evaluation of the Flack parameter.[65]

The enantiomeric excess was determined by HPLC using a chiral stationary phase column

(Column, Chiralcel OD-H, AD-H and OJ-H) or by GC (Chirasil-Dex CB), detailed conditions

are given in the catalysis part.

62

5.2 Synthesis

5.2.1 Synthesis of bis(pentafluorophenyl)borane HB(C6F5)2:[25]

C12HBF10, 346 g / mol

A small portion of Bromopentafluorobenzene (10.0 g, 40.0 mmol) was slowly added to a

Schlenk flask containing magnesium turnings (0.96 g, 40.0 mmol) in anhydrous Et2O (40 mL)

under an argon atmosphere and heated carefully (maximum 40 °C) until the solution turned

turbid. Subsequently, the heating was stopped and the rest of the bromopentafluorobenzene

was added slowly. After the initial reaction had subsided, the solution was stirred for 30

minutes at room temperature. The generated (C6F5)MgBr was added to a solution of BF3.OEt2

(2.5 mL, 20.0 mmol) in anhydrous Et2O (40 mL) at 0 °C within 1 minute. The reaction was

stirred for 10 minutes at 0 °C and for 3 hours at room temperature. After the volatiles were

removed, the product was extracted 5 times with 50 mL of a 5:1 pentane/toluene mixture. The

resulting solutions were collected, the volume was reduced to 10 mL, and then transferred to a

100 mL Young type Schlenk. After complete removal of the solvent, a brownish oil was

obtained.[48]

At 0 °C (CH3)2HClSi (20 mL) was added carefully and the reaction mixture was

stirred for 20 minutes at room temperature. A colourless precipitate (product) and a brown

residue were formed. The mixture was washed with cold pentane to remove the brown

impurity. The white precipitate was recrystallized in anhydrous hot pentane to afford 2.98 g

(43 %) of pure product as a colourless solid.

11B-NMR (96 MHz, CDCl3): δ = 19.6 ppm.

19F-NMR (376 MHz, CDCl3): δ = -132.25 (m, 4F), -147.73 (m, 2F), -158.86 (m, 4F) ppm.

63

5.2.2 Synthesis of bis(tetrafluorophenyl)borane (p-C6F4H)2BH:[27]

C12H3BF8, 309.95 g / mol

A small portion of 1-Bromo-2,3,5,6-tetrafluorobenzene (5.0 g, 22.0 mmol) was slowly added

to a Schlenk flask containing magnesium turnings (0.52 g, 22.0 mmol) in anhydrous Et2O (20

mL) under an argon atmosphere and heated carefully (maximum 40 °C) until the solution

turned turbid. Subsequently, the heating was stopped and the rest of the bromo-2,3,5,6-

tetrafluorobenzene was added slowly. After the initial reaction had subsided, the solution was

stirred for 30 minutes at room temperature. The generated (p-C6F4H)MgBr was added to a

solution of BF3.OEt2 (1.37 mL, 11.0 mmol) in anhydrous Et2O (20 mL) at 0 °C within 1

minute. The reaction was stirred for 10 minutes at 0 °C and for 3 hours at room temperature.

After the volatiles were removed, the product was extracted 5 times with 50 mL of a 5:1

pentane/toluene mixture. The resulting solutions were collected, the volume was reduced to

10 mL, and then transferred to a 100 mL Young type Schlenk. After complete removal of the

solvent a brownish oil was obtained.[48]

At 0 °C (CH3)2HClSi (15 mL) was added carefully

and the reaction mixture was stirred for 20 minutes at room temperature. A colourless

precipitate (product) and a brown residue were formed. The mixture was washed with cold

pentane to remove the brown impurity. The colourless precipitate was recrystallized in dry hot

pentane to afford 1.52 g (45 %) of pure product.

1H-NMR (300 MHz, C6D6): δ = 6.03 (tt, JH-F = 9.5 Hz, JH-F = 7.34 Hz, 2H), 4.52 (br, BH)

ppm.

11B-NMR (96 MHz, C6D6): δ = 20.6 ppm.

13C-NMR (100 MHz, C6D6): δ = 109.2 (t, JC-F = 22.4 Hz, p-C6F5H), 110.8 (br, C6F5H), 144.6

(m, C6F5H), 147.1 (m, C6F5H) ppm.

19F-NMR (282 MHz, C6D6): δ = -136.9 (m, 4F), -133.8 (m, 4F) ppm.

64

5.2.3 Synthesis of (1R,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-en-2-

yltrifluoromethanesulfonate (5):[66]

C11H15F3O3S, 284.00 g / mol

In a Schlenk flask (250 mL) a solution of 4 (6.1 g, 40.0 mmol) in anhydrous THF (10 mL)

was added to a solution of LDA (2M, 20 mL) in anhydrous THF (20 mL) at -78 °C and stirred

for 1 hour. Then a solution of N-phenyltrifluoromethanesulfonimide (15.3 g, 42.8 mmol) in

anhydrous THF (45 mL) was added and the reaction was stirred at 0 °C for 14 hours. The

organic layer was washed with brine and dried over Na2SO4. The residue was purified by

flash chromatography (pentane) affording 7.3 g (75 %) of 5 as a colorless liquid.

1H-NMR (300 MHz, CDCl3): δ = 0.71 (s, 3H), 0.85 (s, 3H), 0.95 (s, 3H), 1.03-1.12 (m, 1H),

1.30-1.22 (m, 1H), 1.65-1.54 (m, 1H), 1.90-1.80 (m, 1H), 2.37 (m, 1H), 5.59 (d, J = 3.9 Hz,

1H) ppm.

13C-NMR (75 MHz, CDCl3): δ = 9.8, 19.3, 20.0, 25.7, 31.2, 50.5, 54.2, 57.3, 118.0, 118.9,

155.6 ppm.

65

5.2.4 Synthesis of 2-[(1R,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-en-2-

yl]pyridine (6):[66]

C15H19N, 213.32 g / mol

In a Schlenk flask (250 mL) a solution of n-BuLi (14.0 mL, 20.0 mmol) was added dropwise

at -78 °C to a solution of 2-bromopyridine (3.2 g, 20.0 mmol) in anhydrous THF (20 mL).

The reaction mixture was stirred at -78 °C for 30 minutes, then a solution of ZnBr2 (13.0 mL,

21.0 mmol) was added dropwise. After 15 min at -78 °C, the reaction mixture was allowed to

warm up to room temperature for 30 minutes. Subsequently, a solution of the alkenyl triflate 5

(2.8 g, 10.0 mmol), Pd(dba)2 (0.12 g, 0.20 mmol), dppf (0.11 g, 0.20 mmol) and LiCl (42.4

mg, 1.0 mmol) in anhydrous THF (10 mL) was added dropwise and the reaction mixture was

heated at 100 ºC overnight. After 24 hours, the THF was removed under reduced pressure.

The formed precipitate was dissolved in Et2O and washed with brine solution. The organic

layer was collected and dried over MgSO4. The crude product was purified by flash

chromatography 1:5 Et2O/pentane, affording 1.32 g (62 %) of 6 as a pale yellow liquid.

1H-NMR (300 MHz, CDCl3): δ = 0.75 (s, 3H), 0.81 (s, 3H), 1.08-0.96 (m, 1H), 1.17 (s, 3H),

1.40-1.28 (m, 1H), 1.68-1.56 (m, 1H), 1.92-1.82 (m, 1H), 2.35 (t, J = 3.6 Hz, 1H), 6.26 (d, J =

3.3 Hz, 1H), 6.97 (m, 1H), 7.20 (m, 1H), 7.48 (m, 1H), 8.47 (m, 1H) ppm.

13C-NMR (75 MHz, CDCl3): δ = 12.8, 14.5, 20.1, 26.0, 32.1, 52.2, 55.3, 57.3, 121.3, 121.5,

135.9, 136.1, 149.4, 149.8, 157.8 ppm.

66

5.2.5 Synthesis of 2-[(1R,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-en-2-

yl]quinoline (8):[67]

C19H21N, 263.37 g / mol

In a Schlenk flask (250 mL), 10 mL of anhydrous THF were added and cooled to -10°C. Then

BuMgCl (2.0 M, 3.2 mmol) and BuLi (1.6 M, 6.4 mmol) were added, and the reaction

mixture was stirred for 1 hour at -10 °C. Then, 2-bromoquinoline (2.0 g, 9.6 mmol) in

anhydrous THF (5 mL) was added at -30 °C and stirred for 1.5 hours at -10 °C. Then ZnBr2

(2.2 g, 9.6 mmol) in anhydrous THF (10 mL) was added at -10 °C and stirred for 30 minutes

at the same temperature. After this, the mixture was slowly warmed to room temperature and

stirred for 30 minutes. Subsequently, a solution of alkenyl triflate 5 (1.2 g, 4.9 mmol),

Pd(dba)2 (0.12 g, 0.34 mmol), dppf (0.19 g, 0.34 mmol) and LiCl (72.0 mg, 1.7 mmol) in

anhydrous THF (10 mL) was added dropwise and the reaction mixture was heated at 100 ºC

overnight. Then THF was removed under reduced pressure, the formed precipitate was

dissolved in Et2O and washed with brine and H2O. The organic layer was collected and dried

over MgSO4. The crude product was purified by flash chromatography 1:5 ethyl

acetate/pentane, affording 0.65 g (50 %) of pure 8 as a colourless solid.

1H-NMR (300 MHz, CDCl3): δ = 0.77 (s, 3H) 0.83 (s, 3H) 1.07-0.98 (m, 1H), 1.35 (s, 3H),

1.48-1.37 (m, 1H), 1.70-1.61 (m, 1H), 1.95-1.84 (m, 1H) 2.39 (t, J = 3.6 Hz, 1H), 6.44 (d, J =

3.6 Hz, 1H), 7.40-7.28 (m, 2H), 7.62-7.50 (m, 2H), 7.70 (m, 1H), 8.20 (m, 1H) ppm.

13C-NMR (75 MHz, CDCl3): δ = 13.1, 19.9, 20.2, 32.1, 26.2, 52.5, 55.7, 57.1, 120.2, 125.9,

127.0, 127.6, 129.4, 130.0, 135.6, 137.8, 148.3, 150.1, 157.5 ppm.

Melting point = 104.3 ºC ± 2; HRMS (ESI, m/z) calcd. For [C19H21N]: 163.1674; found:

164.1739

67

5.2.6 Synthesis of (1R, 4R)-2-(4-bromophenyl)-1,7,7-trimethyl-2-

phenylbicyclo[2.2.1]hept-2-ene (11):[24]

C16H19Br, 291.2 g / mol

In a Schlenk flask (250 mL) a solution of 1,4-dibromobenzene (15.5 g, 65.7 mmol) in

anhydrous THF (10 mL) was slowly added to magnesium turnings (1.6 g, 65.7 mmol) in

anhydrous THF (50 mL) under an argon atmosphere. After the initial reaction had subsided,

the solution was heated for 30 minutes at 50 °C. Then, a solution of 4 (4.0 g, 26.3 mmol) in

anhydrous THF (10 mL) was then added, and the reaction mixture was heated at 100 ºC

overnight. The mixture was cooled in an ice/water bath and quenched with saturated aqueous

NH4Cl (10 mL). The organic layer was separated and the aqueous phase was extracted with

Et2O (3 × 30 mL). The organic phases were combined, dried with Na2SO4, and concentrated

in vacuo. After removal of the solvents, the residue was purified by Kugelrohr distillation

(high vacuum, 80 °C). The residual oil was dissolved in 20 mL of pyridine and the mixture

was cooled in salt/ice bath (-10 °C). Thionyl chloride (3 mL) was slowly added by syringe and

the mixture stirred at 0 °C for 1 hour. Then, the reaction mixture was carefully diluted with

water (0 °C) and extracted with pentane (3 × 30 mL). Subsequently, the extract was washed,

with 10 % HCl, saturated NaHCO3, and saturated aqueous NaCl. The combined organic

phases were dried over Na2SO4. The crude product was purified by column chromatography

on silica gel (pentane) resulting in 3.5 g (45 %) of pure 11 as a colourless solid.

1H-NMR (400 MHz, CDCl3): δ = 0.74 (s, 3H), 0.79 (s, 3H), 0.99 (s, 3H), 1.00 (m, 1H), 1.19

(m, 1H), 1.60 (m, 1H), 1.86 (m, 1H), 2.30 (t, J = 3.8 Hz, 1H), 5.91 (d, J = 3.2 Hz, 1H), 7.25

(d, J = 8.0 Hz, 2H), 7.77 (t, J = 7.7 Hz, 2H) ppm.

13C-NMR (75 MHz, CDCl3): δ = 12.6, 19.6, 19.7, 25.6, 31.9, 51.7, 54.9, 57.2, 120.2, 128.3,

131.2, 132.5, 137.5, 148.8 ppm.

Melting point = 58.0 ºC ± 2; MS: m/z (rel. int.) 291

68

5.2.7 Synthesis of di-mesityl(4-((1S,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-en-

2-yl)phenyl)phosphine (12):

C34H41P, 480.7 g / mol

To a Schlenk flask (100 mL) with a solution of 11 (1.5 g, 5.2 mmol) in anhydrous THF (5

mL), t-BuLi (6.8 mL, 10.4 mmol) was slowly added at -78 °C under an argon atmosphere.

After 1 hour at -30 °C, di-mesitylchlorophosphine (1.0 mL, 5.2 mmol) was slowly added,

stirred for 30 minutes at -78 °C, then warmed slowly to room temperature, and stirred

overnight. Subsequently, THF was removed under vacuo, the residue washed with anhydrous

pentane (3 × 10 mL), and filtrated under argon. Then the residual was washed with anhydrous

methanol (3 × 5 mL) resulting in 1.5 g (60 %) of pure 12 as colourless powder.

1H-NMR (300 MHz, Toluene-d8): δ = 0.75 (s, 3H), 0.92 (s, 3H), 1.07 (s, 3H), 1.00 (m, 1H),

1.28 (m, 1H), 1.59 (m, 1H), 1.87 (m, 1H), 2.14 (s, 6H), 2.27 (s, 12H), 2.28 (s, 1H) 5.90 (d, J

=3.5 Hz, 1H), 6.71 (d, J = 2.3 Hz, 4H), 7.11 (m, 2H ), 7.47 (t, J = 7.8 Hz, 2H) ppm.

13C-NMR (75 MHz, Toluene-d8): δ = 12.7, 19.8, 19.8, 20.9, 23.2, 23.5, 26.0, 52.0, 55.1, 57.2,

126.7, 126.8, 130.5, 130.5, 132.1, 133.9, 134.2, 135.9, 136.0, 137.4, 138.0, 138.1, 138.4,

142.9, 143.0, 143.1, 143.2, 150.0 ppm.

31P-NMR (400 MHz, C6D6): δ = -22.6 ppm.

69

5.2.8 Synthesis of di-mesitylphoshine bis(perfluorophenyl)((1R,2R,3R,4S)-

4,7,7-trimethyl-4-phenyl-bicyclo[2.2.1]heptan-2-yl)hydroborate (13):

C46H42BF10P, 826.59 g / mol

In a thick wall Young type Schlenk flask (100 mL) 12 (900 mg, 1.87 mmol) and (C6F5)2BH

(647 mg, 1.87 mmol) were dissolved in anhydrous pentane (25 mL) and stirred at 100 °C for

around 3 days. The resulting clear solution was evaporated to dryness in vacuo to yield a 1.47

g (95 %) of pure 13 as a bright yellow solid.

1H-NMR (300 MHz, C6D6): δ = 0.57 (s, 3H), 0.76 (s, 3H), 0.87 (s, 3H), 0.87 (m, 1H), 1.10

(m, 1H), 1.21 (m, 1H), 1.49 (m, 2H), 2.10 (s, 6H), 2.22 (s, 12H), 3.15 (d, J = 7.2 Hz, 2H),

6.72 (m, 6H), 7.20 (t, J = 7.4 Hz, 2H) ppm.

13C-NMR (75 MHz, C6D6): δ = 13.9, 14.1, 18.9, 19.5, 20.8, 22.8, 23.1, 28.2, 30.2, 34.3, 48.9,

50.9, 51.9, 52.6, 54.3, 57.6, 128.5, 128.6, 130.5, 130.7, 133.5, 134.1, 136.4, 136.6, 138.2,

140.0, 142.8, 142.9, 143.0, 143.1 ppm. The carbon atoms bonded to boron and the quaternary

carbon of C6F5 ring were not observed.

19F-NMR (282 MHz, C6D6): δ = -130.7 (d, JF-F = 24.0 Hz, 4F), -150.0 (t, JF-F = 18.0 Hz, 2F), -

160.7 (t, JF-F = 19.6 Hz, 4F) ppm.

31P-NMR (121 MHz, C6D6): δ = -23.1 ppm.

70

5.2.9 Synthesis of di-tert-butyl(4-((1R,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-

en-2yl)-phenyl)phosphine (14):[36]

C24H37P, 356.2633 g / mol

In a Schlenk flask (100 mL) a solution of 11 (1.5 g, 5.2 mmol) in anhydrous THF (5 ml) was

prepared and t-BuLi (6.8 ml, 10.4 mmol) was slowly added at -78 °C under an argon

atmosphere. After 1 hour at –30 °C, di-tert-butylchlorophosphine (1.0 mL, 5.2 mmol) was

added, stirred for 30 minutes at -78 °C, then warmed to room temperature, and stirred

overnight. Subsequently, THF was removed under vacuo, the residue washed with anhydrous

pentane (3 × 10 mL) and filtrated under argon. Then the residue was washed with anhydrous

methanol (3 × 5 mL) to yield 1.1 g (60 %) of pure 14 as colourless powder.

1H-NMR (400 MHz, C6D6): δ = 0.73 (s, 3H), 0.94 (s, 3H), 0.99 (s, 3H), 1.00 (m, 1H), 1.21 (d,

J = 1.8, 9H), 1.24 (d, J = 2.0, 9H), 1.32 (m, 1H), 1.59 (m, 1H), 1.87 (m, 1H), 2.27 (t, J = 3.1

Hz, 1H), 5.96 (d, J = 3.9 Hz, 1H), 7.03 (d, J = 7.8 Hz, 2H), 7.33 (d, J = 8.8 Hz, 2 H) ppm.

13C-NMR (75 MHz, Toluene-D8): δ = 12.7, 19.8, 19.8, 26.0, 30.9, 30.7, 32.0, 32.2, 32.2, 52.1,

55.1, 57.2, 126.0, 126.1, 132.4, 135.5, 135.8, 136.7, 139.4, 150.0 ppm.

31P-NMR (400 MHz, C6D6): δ = 37.9 ppm.

Melting point = 96.5 ºC ± 2; HRMS (ESI, m/z) calcd. For [C24H37P]: 356.2633; found:

357.2716.

71

5.2.10 Synthesis of di-tert-butylphosphonium bis(perfluorophenyl)

((1R,2R,3R,4S)-4,7,7-trimethyl-4-phenyl-bicyclo[2.2.1]heptan-2-yl)

hydroboratborate (16):[36]

C36H40BF10P, 704.5 g / mol

In a Young-type Schlenk flask (100 mL), (C6F5)2BH (242.6 mg, 0.7 mmol) and 14 (0.7 mmol)

were dissolved in anhydrous pentane (5 mL) and stirred at 100 °C. Without purification, the

solution of 15 in anhydrous pentane was degassed three times with freeze-pump-thaw cycles

and refilled with H2 (1 bar) at liquid nitrogen temperature. The reaction was allowed to stir at

room temperature for 48 hours. The product precipitated during this time as a colourless solid.

The supernatant was decanted and the residue was washed with anhydrous pentane.

Purification on column chromatography using silica and dichloromethane as eluent resulted in

0.2 g (40 %) of pure 16. Crystals suitable for X-ray diffraction were grown from a layered

dichloromethane/pentane solution.

1H-NMR (600 MHz, CD2Cl2): δ = 0.62 (s, 3H), 0.91 (s, 3H), 1.13, (m, 1H), 1.38 (s, 3H),1.41

(m, 1H), 1.49 (d, J =1.6 Hz, 9H), 1.51 (d, J = 1.6 Hz, 9H), 1.59 (m, 1H), 1.68 (s, 1H), 1.89 (t,

J = 8.7 Hz, 1H,), 1.96 (m, 1H), 2.85 (br, BH), 3.0 (d, J = 9.1 Hz, 1H), 5.71 (d, JP-H = 477 Hz,

PH), 7.38 (m, 2H), 7.49 (m, 2H) ppm.

11B-NMR (96 MHz, CD2Cl2): δ = -19.25 (d, JB-H = 81.6 Hz) ppm.

13C

-NMR (150 MHz, CD2Cl2): δ = 14.6, 20.7, 22.0, 27.5, 28.8, 33.1, 34.5, 34.8, 50.3, 50.6,

51.4, 59.5, 107.5, 132.1, 157.2 ppm. The carbon atoms bonded to boron and quaternary

carbon of C6F5 ring were not observed.

19F{

1H}-NMR (376 MHz, CD2Cl2): δ = -132.36 (d, JF-F = 21.9 Hz, 2F), -132.83 (dm, JF-F =

19.3 Hz, 2F), -165.73 (t, JF-F = 23.4 Hz, 1F), -165.93 (t, JF-F = 20.8 Hz, 1F), -167.61 (m, 2F), -

167.82 (m, 2F) ppm.

31P{

1H}-NMR (242 MHz, CD2Cl2): δ = 53.6 ppm.

72

31P-NMR (122 MHz, CD2Cl2): δ = 53.6 (dm, JP-H = 477.0 Hz) ppm.

5.2.11 X-Ray Single crystal analysis of 16:[36]

Crystal data

Chemical formula C36H40BF10P

Mr 704.47

Crystal system, space group Orthorhombic, P212121

Temperature (K) 100

a, b, c (Å) 12.0634 (9), 16.7746 (13), 18.2959 (14)

V (Å3) 3702.3 (5)

Z 4

Radiation type Mo K

(mm-1) 0.30

Crystal size (mm) 0.23 × 0.15 × 0.15

Data collection

Diffractometer CCD area detector diffractometer

Absorption correction Multi-scan SADABS

Tmin, Tmax 0.935, 0.957

No. of measured, independent and

observed [I > 2(I)] reflections

45219, 7676, 6408

Rint 0.081

(sin /)max (Å-1) 0.631

Refinement

R[F2 > 2(F2)], wR(F2), S 0.044, 0.099, 1.03

No. of reflections 7676

No. of parameters 477

H-atom treatment H atoms treated by a mixture of independent and

constrained refinement

max, min (e Å-3) 0.29, -0.27

Absolute structure Flack H D (1983), Acta Cryst. A39, 876-881

Absolute structure parameter 0.00 (6)

73

5.2.12 Synthesis of (1R,4R)-1,7,7-trimethyl-2-(2-naphthyl)-bicyclo[2.2.1]hept-2-

ene (24):[20]

C20H22, 262.38 g / mol

A solution of 2-bromonaphthalene (12.4 g, 60.0 mmol) in anhydrous THF (10 mL) was

slowly added to a Schlenk flask containing magnesium turnings (1.5 g, 60.0 mmol) in

anhydrous THF (50 mL). After the initial reaction had subsided, the solution was heated for

30 minutes at 50 °C. Then a solution of R-(+)-camphor 4 (4.6 g, 30.0 mmol) in anhydrous

THF (10 mL) was then added. The reaction mixture was heated at 100 ºC overnight, then it

was cooled in an ice/water bath and quenched with saturated aqueous NH4Cl (10 mL). The

organic layer was separated and the aqueous phase was extracted with diethyl ether (3 × 30

mL). The organic phases were combined, dried with Na2SO4, and concentrated in vacuo. The

residue was dissolved in 20 mL of pyridine and the mixture was cooled in a salt/ice bath (-10

°C). Thionyl chloride (1 mL) was slowly added by syringe and then the mixture was stirred at

0 °C for 1 hour. The reaction mixture was diluted with water and extracted with pentane (3 ×

30 mL). The extracted phases were washed with 10 % HCl, saturated aqueous NaHCO3, and

saturated aqueous NaCl (brine solution). The combined organic phases were dried over

Na2SO4. Solvents were removed under vacuum and the crude product was purified by column

chromatography on silica gel with pentane as eluent resulting in 2.9 g (57 %) of pure 24 as a

colourless solid.

1H-NMR (400 MHz, C6D6): δ = 0.77 (s, 3H), 1.00 (s, 3H), 1.15 (m, 1H), 1.16 (s, 3H), 1.42

(m, 1H), 1.64 (m, 1H), 1.91 (m, 1H), 2.32 (t, J = 3.4 Hz, 1 H), 6.03 (d, J = 3.4 Hz, 1H), 7.22-

7.32 (m, 2H), 7.36-7.42, (m, 1H), 7.58-7.70 (m, 3H), 7.75 (s, 1H) ppm.

13C-NMR (100 MHz, C6D6): δ = 12.8, 19.7, 19.8, 26.0, 32.2, 52.0, 55.2, 57.2, 125.1, 125.5,

125.9, 126.1, 127.8, 128.1, 132.3, 132.8, 134.0, 136.3, 150.3 ppm.


74

5.2.13 Synthesis of bis(perfluorophenyl)((1R,2R,3R,4S)-4,7,7-trimethyl-3-

(naphthalen-2-yl)bicyclo[2.2.1]heptan-2-yl)borane (27).[20]

C32H23BF10, 608.17 g / mol

In a glove box a suspension of (C6F5)2BH (345.9 mg, 1.0 mmol) and 24 (262.4 mg, 1.0 mmol)

in anhydrous pentane (5 mL) was prepared in a Young type Schlenk flask (50 mL). The

reaction mixture was stirred in an oil bath maintained at 100 °C for 72 hours. The resulting

clear solution was evaporated to dryness in vacuo to yield 0.58 g (95 %) of pure 22 as a dark

red solid.

1H-NMR (300 MHz, C6D6): δ = 0.68 (s, 3H), 0.82 (s, 3H), 0.95 (s, 3H), 1.10-1.21 (m, 1H),

1.60-1.78 (m, 2H), 1.55-1.98 (m, 1H), 2.17-2.28 (m, 2H), 3.36 (d, J = 8.6 Hz, 1H), 7.03-7.25

(m, 3H), 7.40-7.59 (m, 4H) ppm.

11B-NMR (96 MHz, C6D6): δ = 75.2 ppm.

13C-NMR (75 MHz, C6D6): δ = 14.0, 19.0, 19.5, 28.4, 30.6, 49.1, 51.1, 52.6, 55.1, 58.3 (brs,

B-C), 125.8, 126.4, 127.0, 127.5, 127.7, 127.8, 132.7, 133.5, 137.9, ppm. Quaternary carbon

of C6F5 ring was not observed.

19F-NMR (282 MHz, C6D6): δ = -130.7 (dm, 4F), -150.0 (t, JF-F = 20.1 Hz, 2F), -161.1 (m, 4F)

ppm.

75

5.2.14 Synthesis of bis(perfluorophenyl)((1R,2R,3R,4S)-4,7,7-trimethyl-3-

(naphthalen-2-yl)bicyclo[2.2.1]heptan-2-yl)hydroborate tri-tert-

butylphosphonium salt (3):[20]

C44H52BF10P, 811.6 g / mol

In a glovebox 27 (608.3 mg, 1.0 mmol) and tri-tert-butylphosphine (202 mg, 1.0 mmol) were

dissolved in pentane (20 mL) in a 100 mL Young-type Schlenk flask. The solution was

degassed three times with freeze-pump thaw cycles and refilled with H2 (1 bar) at liquid

nitrogen temperature. The reaction was allowed to stir at room temperature for 72 hours. The

product precipitated during this time as a colorless solid. The supernatant was decanted and

the residue was washed with pentane and dried in vacuo to yield 0.496 g (61 %) of pure 3 as a

colourless solid.[20]

1H-NMR (300 MHz, CD2Cl2): δ = 0.64 (s, 3H), 0.89 (s, 3H), 1.08, (m, 1H), 1.37 (s, 3H), 1.56

(d, J = 15.5, 27H), 1.56-1.69 (m, 3H), 1.93 (m, 2H), 2.94 (d, J = 8.6 Hz, 1H), 3.01 (br, B-H,

1H), 4.47- 5.43 (d, JP-H = 433.3 Hz) 7.20-7.80 (m,7H) ppm.

11B-NMR (96 MHz, CD2Cl2): δ = -18.8 (d, JB-H = 85.0 Hz) ppm.

13C{

1H}-NMR (75 MHz, CD2Cl2): δ = 15.3, 21.4, 22.6, 29.4, 30.3, 33.7, 37.9, 50.6, 50.9,

51.0, 59.1, 124.3, 125.1, 125.4, 127.3, 127.6, 127.7, 129.9, 131.9, 133.5, 144.2 ppm. The

carbon atoms bonded to boron atom and the quaternary carbon of C6F5 ring were not

observed.

19F{

1H}-NMR (282 MHz, CD2Cl2): δ = -132.2 (dm, JF-F = 23.4 Hz, 2F), -132.8 (dm, JF-F =

23.2 Hz, 2F), -166.2 (t, JF-F = 20.6 Hz, 1F), -167.4 (t, JF-F = 20.6 Hz, 1F), -167.7 (m, 2F), -

168.5 (m, 2F) ppm.

31P{


31P-NMR (121 MHz, CD2Cl2): δ = 59.7 (dm, JP-H = 430 Hz) ppm.

76

5.2.15 Synthesis of (2,3,5,6-tetrafluorophenyl)((1R,2R,3R,4S)-4,7,7-trimethyl-

3-(naphthalen-2-yl)bicyclo[2.2.1]heptan-2-yl)borane, tri-tert-butylphosphonium

salt (26):

C44H53BF8P, 775.60 g / mol

In a glove box a suspension of (p-C6F4H)2BH (295.36 mg, 0.95 mmol) and 24 (250 mg, 0.95

mmol) in anhydrous pentane (25 mL) in a 100 mL Young-type Schlenk flask, was prepared.

The reaction mixture was stirred for 72 hours at 100 °C to give compound 25. Then, in a

glove box t-Bu3P (0.95 mmol) was added with a syringe. The solution was degassed three

times with freeze-pump-thaw cycles and refilled with H2 (1 bar) at liquid nitrogen

temperature. The reaction was allowed to stir at room temperature for 30 hours. The product

precipitated during this time as a colorless solid. The supernatant was decanted and the

residue was washed with pentane and dried in vacuo affording 0.32 g (53 %) of pure 26 as a

colourless solid.

1H-NMR (600 MHz, CD2Cl2): δ = 0.66 (s, 3H), 0.92 (s, 3H), 1.1 (t, J = 10.7 Hz, 1H), 1.42 (s,

3H), 1.60 (d, J = 16 Hz, 27H), 1.62 (m, 2H), 1.98-2.04 (m, 2H), 3.00 (br, B-H, 1H), 3.03 (d, J

= 8.8 Hz, 1H), 4.77- 5.73 (d, JP-H = 438.3 Hz), 5.76 (m, 1H), 6.66 (m, 1H), 7.30-7.36 (m, 3H),

7.50 (t, J = 8.8 Hz, 2H), 7.70 (d, J = 8.3 Hz, 2H) ppm.

11B-NMR (96 MHz, CD2Cl2): -25.0 ppm.

13C-NMR (150 MHz, CD2Cl2): δ = 15.0, 21.1, 22.2, 29.0, 29.9, 33.3, 50.1, 50.7, 53.4, 58.6,

98.6, 99.3, 123.7, 124.4, 124.8, 126.9, 127.3, 129.6, 131.6, 133.2, 136.4, 143.6, 143.9, 144.3,

145.2, 145.9, 146.8, 147.8, 148.3, 149.4 ppm.

19F{

1H}-NMR (281 MHz, CD2Cl2): δ = -132.76 (m, 2F), -133.31 (m, 2F), -144.63 (m, 2F), -

145.59 (m, 2F) ppm.

31P{


77


5.2.16 X-Ray Single crystal analysis of 26:

Crystal data

Chemical formula C44H54BF8P

Mr 776.65


Temperature (K) 100

a, b, c (Å) 14.2000 (14), 14.8231 (14), 19.1578 (18)

V (Å3) 4032.5 (7)

Z 4

Radiation type Mo K

(mm-1) 0.14

Crystal size (mm) 0.15 × 0.15 × 0.15

Data collection



67968, 7175, 5699

Rint 0.093

(sin /)max (Å-1) 0.598

Refinement

R[F2 > 2(F2)], wR(F2), S 0.053, 0.112, 1.05



H-atom treatment H atoms treated by a mixture of independent and constrained

refinement

max, min (e Å-3) 0.24, -0.20

Absolute structure Flack x determined using 2078 quotients [(I+)-(I-)]/[(I+)+(I-)]

(Parsons and Flack (2004), Acta Cryst. A60, s61).


78

5.2.17 Synthesis of 1,1'-(4,4'-((4,7,7-trimethyl-3-(naphthalen-2-

yl)bicyclo[2.2.1]heptan-2-yl)boranediyl)bis(2,3,5,6-tetrafluoro-4,1phenylene))

bis((2R,5R)2,5dimethylphospholane) (28):

C44H47BF8P2, 800.50 g / mol

In a 50 mL Schlenk tube a solution of (2R,5R)-2,5-dimethyl-1-(trimethylsilyl)phospholane

(165.7 mg, 0.88 mmol) in anhydrous pentane (2 mL) was added dropwise to a solution of 27

(243.3 mg, 0.4 mmol) in dry pentane (10 mL). The reaction mixture immediately turned

colorless and was stirred for an additional hour. Then the solution was cooled to -78 °C. The

pentane phase was carefully transferred to a 50 mL Schlenk tube, all volatiles were removed

under vacuo and the residue was further dried for 2 hours at 60 °C under vacuo, affording

304.0 mg (94 %) of pure 28 as a colourless solid.

1H-NMR (600 MHz, C6D6): δ = 0.51 (brs, 3H), 0.69 (s, 3H), 0.76 (s, 3H), 0.89 (m, 1H), 1.00-

1.04 (m, 6H), 1.10 (dd, J = 7.3 Hz, 21.4 Hz, 6H), 1.26 (m, 2H), 1.69 (m, 4H), 1.94 (m, 2H),

2.02 (m, 4H), 2.36 (m, 1H), 2.47 (d, J = 7.3 Hz, 1H), 2.84 (m, 2H), 3.57 (m, 1H), 7.16-7.20

(m, 3H), 7.49-7.54 (m, 4H) ppm (one resonance from the phospholane moiety was not

observed).

11B-NMR (96 MHz, C6D6): δ = -16.3 (br) ppm.

13C{

1H}-NMR (151 MHz, C6D6): δ = 14.6, 15.6, 19.4, 20.1, 22.0 (d, JCP = 37.5 Hz), 28.9,

31.1, 32.2, 36.1 (d, JC-P = 15.0 Hz), 37.1, 38.6, 51.6, 52.8, 55.2, 58.0, 119.7, 121.2, 125.9,

126.5, 128.1, 128.4, 128.7, 133.2, 134.1, 138.7, 144.9 (dm, JC-F = 240.1 Hz, C6F4), 148.3 (dm,

JC-F = 237.6 Hz, C6F4) ppm.

19F{

1H}-NMR (282 MHz, C6D6): δ = -129.0 (br), -131.3 (br) ppm.

31P-NMR (243 MHz, C6D6): δ = 4.0 (t, J = 31.2 Hz) ppm.

79

5.2.18 Synthesis of 1-((1S,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-en-2-yl)-4-

((1S,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-en-2-yl)benzene (30):

C26H34, 346 g / mol

In a Schlenk flask (250 mL) a solution of 11 (1.7 g, 5.7 mmol) in anhydrous THF (15 ml) was

cooled to -78 °C and t-BuLi (1.7M, 12.5 mmol) was carefully added. Then the reaction

mixture was stirred between -30 °C and -15 °C for 3 hours. In a second Schlenk dry CeCl3

(2.1 g, 8.5 mmol) was weighed and dried by heating at 630 °C under vacuum. Then CeCl3 was

mixed with anhydrous THF (30 mL) and stirred for 1 hour. R-(+)-camphor 4 (1.3 g, 8.5

mmol) was added to the solution and stirred for 2.5 hours until a yogurt like mixture formed.

Using a cannula and under argon atmosphere, the lithiated alkene was added drop wise to the

mixture at 0 °C. The reaction was stirred over night at room temperature. The mixture was

cooled in an ice/water bath and then quenched with saturated aqueous NH4Cl (10 mL). The

organic layer was separated and the aqueous phase was extracted with Et2O (3 × 30 mL). The

organic phases were combined, dried over Na2SO4, and concentrated in vacuo. After removal

of the solvent, the residue was purified by Kugelrohr distillation (high vacuum, 80 °C). The

residual oil was dissolved in 20 mL of pyridine and the mixture was cooled in a salt/ice bath

(-10 ºC). Thionyl chloride (2 mL) was slowly added by syringe, and the mixture stirred at 0

°C for 1 h. Then the reaction mixture was carefully diluted with H2O and extracted with

pentane (3 × 30 mL). The pentane phase was washed with 10 % HCl, saturated NaHCO3, and

brine solution. The combined organic phases were dried over Na2SO4. The crude product was

purified by column chromatography on silica gel (eluent: pentane) affording 1.3 g (66 %) of

pure 30 as a colourless solid.

1H-NMR (300 MHz, CD2Cl2 ): δ = 0.74 (s, 6H), 0.8 (s, 6H), 1.00 (s, 6H), 1.00 (m, 2H), 1.22

(m, 2H), 1.6 (m, 2H), 1.87 (m, 2H), 2.3 (t, J = 3.5 Hz, 2H), 5.88 (d, J = 3.1 Hz, 2H), 7.1-7.17

(m, 4H) ppm.

80

13C-NMR (75 MHz, CD2Cl2): δ = 12.9, 19.8, 19.9, 26.0, 32.3, 52.1, 52.2, 57.4, 126.7, 127.0,

128.4, 131.8, 137.1, 150.1 ppm.


5.2.19 Synthesis of para-di-bis(perfluorophenyl)((1R,2R,3R,4S)-4,7,7-

trimethyl-3-(phenyl-2-yl)bicyclo[2.2.1]heptan-2-yl)borane (31):

C50H36B2F20, 1038 g / mol

In a Young type Schlenk flask (100 mL) 30 (0.5 g, 1.5 mmol) and (C6F5)2BH (1.0 g, 2.9

mmol) were dissolved in anhydrous pentane (40 mL) and stirred at 110 °C for 3 days. Then

the reaction mixture was slowly cooled without stirring and the product crystalized as a

colourless solid, affording 0.8 g (52 %) of pure 31.

1H-NMR (600 MHz, CD2Cl2): δ = 0.69 (s, 6H), 0.89 (s, 6H), 0.97 (s, 6H), 1.32 (t, J = 12.3

Hz, 2H), 1.53 (m, 2H), 1.65 (m, 2H), 2.00-2.1 (m, 4H), 2.2 (d, J = 3.1 Hz, 2H), 3.05 (d, J =

7.7 Hz, 2H), 6.87 (s, 4H) ppm.

11B-NMR (96 MHz, CD2Cl2): δ = 41.0 ppm.

13C{

1H}-NMR (150 MHz, CD2Cl2): δ = 13.3, 18.7, 19.2, 27.7, 30.3, 48.8, 50.3, 52.2, 54.0,

58.4, 113.2 (t, JC-F = 26.6 Hz), 128.0, 137.2 (dt, JC-F = 252.7 Hz, JC-F = 14.3 Hz), 138.3, 141.9

(d, JC-F = 245.4 Hz), 144.5 (d, JC-F = 241.8 Hz) ppm.

19F{

1H}-NMR (282 MHz, CD2Cl2): δ = -130.7 (s, 8F), -151.9 (s, 4F), -162.2 (t, JF-F = 17.8

Hz, 8F) ppm.

81


Crystal data

Chemical formula C50H36B2F20

Mr 1038.41

Crystal system, space group Monoclinic, P21

Temperature (K) 100

a, b, c (Å) 11.2408 (7), 13.0206 (8), 15.2199 (9)

(°) 95.844 (2)

V (Å3) 2216.0 (2)

Z 2

Radiation type Mo K

(mm-1) 0.15

Crystal size (mm) 0.30 × 0.19 × 0.06

Data collection



Tmin, Tmax 0.957, 0.991



27313, 9109, 7069

Rint 0.067

(sin /)max (Å-1) 0.626

Refinement

R[F2 > 2(F2)], wR(F2), S 0.049, 0.122, 1.03



No. of restraints 1

H-atom treatment H-atom parameters constrained

max, min (e Å-3) 0.31, -0.26


Absolute structure parameter -0.2 (5)

82

5.2.21 Synthesis of di-tri-tert-butylphosphonium para-di-

bis(perfluorophenyl)((1R,2R,3R,4S)-4,7,7-trimethyl-3-(phenyl-2-

yl)bicyclo[2.2.1]heptan-2-yl)hydroborate (32).

C74H94B2F20P2, 1447 g / mol

In a Young type Schlenk flask (100 mL), 31 (0.7 g, 0.67 mmol) and t-Bu3P (0.27 g, 1.3

mmol) were dissolved in anhydrous pentane (25 mL). The solution was degassed three times

with freeze-pump-thaw cycles and refilled with H2 (1 bar) at liquid nitrogen temperature.

Then the reaction was stirred at room temperature for 30 hours, during this time the product

precipitated as a colorless solid. The supernatant was decanted, the residue washed with

anhydrous pentane and dried in vacuo affording 339 mg (35 %) of pure 32 as a colourless

solid. Crystals suitable for X-ray diffraction were grown from a layered


1H-NMR (600 MHz, CD2Cl2): δ = 0.42 (s, 6H), 0.74 (s, 9H), 1.18 (s, 9H), 1.45-1.51 (m, 6H),

1.57 (d, J = 15.27, 54H), 2.56 (d, J = 8.6 Hz, 2H), 4.87 (d, JP-H = 431.2 Hz, PH), 6.54 (s, 4 H)

ppm.

11B-NMR (96 MHz, CD2Cl2): δ = -18.6 ppm.

13C-NMR (150 MHz, CD2Cl2): δ = 14.2, 14.8, 21.5, 22.8, 28.6, 30.3, 34.0, 34.5, 38.0 (d, J =

27.16 Hz, P-C), 50.1, 50.4, 56.0, 57.8, 127.5, 141.0 ppm. The carbon atoms bonded to boron

atom and the quaternary carbon of C6F5 ring were not observed.

19F{

1H}-NMR (282 MHz, CD2Cl2): δ = -131.9 (m, 4F), -132.0 (m, 4F), -165.1 (t, JF-F = 20.4

Hz, 2F), -167.4 (t, JF-F = 20.3 Hz, 2F), -167.93 (m, 8F) ppm.


31P{


83


Crystal data

Chemical formula C50H38B2F20·2(C12H28P)·CH2Cl2

Mr 1531.98


Temperature (K) 100

a, b, c (Å) 12.8666 (9), 19.8954 (15), 30.004 (2)

V (Å3) 7680.7 (9)

Z 4

Radiation type Mo K

(mm-1) 0.22

Crystal size (mm) 0.30 × 0.19 × 0.06

Data collection



Tmin, Tmax 0.928, 0.983



92079, 15533, 10565

Rint 0.144

(sin /)max (Å-1) 0.626

Refinement

R[F2 > 2(F2)], wR(F2), S 0.064, 0.138, 1.04




max, min (e Å-3) 0.29, -0.38


Absolute structure parameter -0.08 (8)

84

5.2.23 Synthesis of (1S,4R)-2-(3-bromophenyl)-1,7,7-trimethylbicyclo

[2.2.1]hept-2-ene (33):

C16H19Br, 291.2 g / mol

In a Schlenk flask (500 mL) a solution of 1,3-dibromobenzene (23.3 g, 98.6. mmol) in

anhydrous Et2O (200 mL) was slowly added to magnesium turnings (2.4 g, 98.6 mmol) in

anhydrous Et2O (50 ml) under an argon atmosphere. After the initial reaction had subsided,

the solution was heated for 30 minutes. In a second Schlenk dry CeCl3 (16.2 g, 65.7 mmol)

was weighed and dried by heating at 630 °C under vacuum. Then CeCl3 was mixed with

anhydrous THF (200 mL) and stirred for 1 hour. R-(+)-camphor 4 (10 g, 65.7 mmol) was

added and stirred for 2.5 hours until a yogurt like mixture formed. Using a cannula and under

argon atmosphere, the generated 2-Bromophenyl magnesium bromide was added drop wise to

the mixture of CeCl3 and R-(+)-camphor at 0 °C. The reaction was stirred over night at room

temperature. The mixture was cooled in an ice/water bath and quenched with saturated

aqueous NH4Cl (30 mL). The organic layer was separated and the aqueous phase was

extracted with Et2O (3 × 60 mL). The organic phases were combined, dried over Na2SO4, and

concentrated in vacuo. After removal of the solvent, the residue was purified by Kugelrohr

distillation (high vacuum, 80 °C). The residual oil was dissolved in 40 mL of pyridine and the

mixture was cooled in a salt/ice bath (-10 °C). Thionyl chloride (4 mL) was slowly added by

syringe and the mixture stirred at 0 °C for 1 hour. Then the reaction mixture was carefully

diluted with H2O (0 °C) and extracted with pentane (3 × 30 mL). Subsequently, the extract

was washed with 10 % HCl, saturated NaHCO3, and saturated aqueous NaCl. The combined

organic phases were dried over Na2SO4. The crude product was purified by column

chromatography on silica gel (pentane) resulted in 9.9 g (52 %) of pure 33 as a colorless

liquid.

1H-NMR (400 MHz, CDCl3): δ = 0.71 (s, 3H), 0.77 (s, 3H), 0.98 (s, 3H), 1.00 (m, 1H), 1.17

(m, 1H), 1.57 (m, 1H), 1.84 (m, 1H), 2.28 (t, J = 3.8 Hz, 1H), 5.91 (d, J = 3.3 Hz, 1H), 7.06

(m, 2H), 7.20-7.30 (m, 2H) ppm.

85

13C-NMR (75 MHz, CDCl3): δ = 12.7, 19.8, 19.9, 25.9, 32.3, 52.2, 55.4, 57.6, 122.5, 125.7,

129.6, 129.9, 130.0, 133.6, 141.3, 149.0 ppm.

MS: m/z (rel. int.) 291

5.2.24 Synthesis of 1-((1R,4S)-1,7,7-trimethylbicyclo[2.2.1]hept-2-en-2-yl)-3-

((1S,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-en-2-yl)benzene (35):

C26H34, 346 g / mol

In a Schlenk flask (250 mL) a solution 33 (1g, 3.5 mmol) in anhydrous Et2O (15 mL) was

cooled to -78°C and t-BuLi (1.7 M, 7.6 mmol) was carefully added. Then the reaction mixture

was stirred at -30°C to -15°C for 3 hours. In a second Schlenk dry CeCl3 (1.3g, 5.2 mmol) was

weighed and dried by heating at 630 °C under vacuum. Then CeCl3 was mixed with

anhydrous THF (30 mL), stir for 1 hour then add R-(+)-camphor 4 (0.8g, 5.2 mmol) and

stirred for 2.5 hours until a yogurt like mixture formed. Using a cannula and under argon

atmosphere, the lithiated alkene was added drop wise to the mixture of CeCl3 and R-(+)-

camphor at 0 °C. The reaction was stirred over night at room temperature. The mixture was

cooled in an ice/water bath and then quenched with saturated aqueous NH4Cl (10 mL). The

organic layer was separated and the aqueous phase was extracted with Et2O (3 × 30 mL). The

organic phases were combined, dried over Na2SO4, and concentrated under vacuo. After

removal of the solvent, the residue was purified by Kugelrohr distillation (high vacuum, 80

°C). The residual oil was dissolved in 25 mL of pyridine and the mixture was cooled in a

salt/ice bath (-10 °C). Thionyl chloride (2 mL) was slowly added by syringe and the mixture

stirred at 0 °C for 1 hour. Then the reaction mixture was cooled to 0 °C and carefully diluted

with water and extracted with pentane (3 × 30 mL). Subsequently, the extract was washed

with 10 % HCl, saturated NaHCO3, and saturated aqueous NaCl. The combined organic

phases were dried over Na2SO4. The crude product was purified by column chromatography

on silica gel (pentane) resulted in 0.8 g of pure 35 (67 %) as a colourless solid.

86

1H-NMR (300 MHz, CD2Cl2 ): δ = 0.84 (s, 6H), 0.91 (s, 6H), 1.11 (s, 6H), 1.1 (m, 2H), 1.32

(m, 2H), 1.68 (m, 2H), 1.96 (m, 2H), 2.39 (t, J = 3.5 Hz, 2H), 5.38 (d, J = 3.2 Hz, 2H), 7.10-

7.25 (m, 4H) ppm.

13C-NMR (75 MHz, CD2Cl2): δ = 12.9, 19.8, 19.9, 26.0, 32.3, 52.1, 55.3, 57.4, 125.1, 125.2,

128.1, 132.0, 138.8, 150.2 ppm.

5.2.25 Synthesis of meta-di-bis(perfluorophenyl)(1R,2R,3R,4S)-4,7,7-trimethyl-

3-(phenyl-2-yl)bicyclo[2.2.1]heptan-2-yl) borane (36):

C50H36B2F20, 1038 g / mol

In a Young type thick glass Schlenk flask (100 mL) a solution of 35 (0.45 g, 1.3 mmol) and

(C6F5)2BH (0.91 g, 2.6 mmol) was dissolved in anhydrous pentane (40 mL) and stirred at 110

°C for 3 days. Then the reaction was slowly cooled without stirring and the product

crystalized as a colourless solid, affording 0.8 g (60 %) of pure 36.

1H-NMR (600 MHz, CD2Cl2 ): δ = 0.63 (s, 6H), 0.91 (s, 6H), 0.97 (s, 6H), 1.28 (t, J = 12.3

Hz, 2H), 1.43 (m, 2H), 1.64 (m, 2H), 2.00 (m, 4H), 2.2 (d, J = 3.1 Hz, 2H), 3.10 (d, J = 7.5

Hz, 2H), 6.73 (s, 1H), 6.88 (d, J = 7.4 Hz, 2H), 7.12 (t, J = 7.7 Hz, 1 H) ppm.

11B-NMR (96 MHz, CD2Cl2): δ = 41.9 ppm.

13C{

1H}-NMR (150 MHz, CD2Cl2): δ = 13.3, 18.7, 19.2, 27.7, 30.1, 48.8, 50.5, 52.2, 54.0,

58.4, 113.2 (t, JC-F = 26.6 Hz), 126.6, 127.2, 129.7, 137.8 (dt, JC-F = 252.7 Hz, JC-F = 14.7 Hz),

139.7, 142.1 (d, JC-F = 249.7 Hz), 144.7 (d, JC-F = 245.1 Hz) ppm.

19F{

1H}-NMR (282 MHz, CD2Cl2): δ = -130.7 (s, 8F), -151.6 (s, 4F), -162.0 (t, JF-F = 17.7

Hz, 8F) ppm.

87


Crystal data

Chemical formula C50H36B2F20

Mr 1038.41

Crystal system, space group Trigonal, P3221

Temperature (K) 100

a, c (Å) 11.0309 (10), 31.708 (3)

V (Å3) 3341.3 (5)

Z 3

Radiation type Mo K

(mm-1) 0.15

Crystal size (mm) 0.30 × 0.13 × 0.12

Data collection



Tmin, Tmax 0.957, 0.983



40771, 4569, 3479

Rint 0.108

(sin /)max (Å-1) 0.625

Refinement

R[F2 > 2(F2)], wR(F2), S 0.047, 0.095, 1.05




max, min (e Å-3) 0.21, -0.21



88

5.2.27 Synthesis of di-tri-tert-butylphosphonium meta-di-

bis(perfluorophenyl)((1R,2R,3R,4S)-4,7,7-trimethyl-3-(phenyl-2-

yl)bicyclo[2.2.1]heptan-2-yl)hydroborate (37).

C74H94B2F20P2, 1447 g / mol

In a Young type Schlenk flask (100 mL), 36 (0.7 g, 0.67 mmol) and t-Bu3P (0.27 g, 1.3

mmol) were dissolved in anhydrous pentane (25 mL). The solution was degassed three times

with freeze-pump-thaw cycles and refilled with H2 (1 bar) at liquid nitrogen temperature.

Then the reaction was stirred at room temperature for 30 hours, during this time the product

precipitated as a colourless solid. The supernatant was decanted, the residue washed with

anhydrous pentane and dried in vacuo affording 291 mg (30 %) of pure 37 as a colourless

solid. Crystals suitable for X-ray diffraction were grown from a layered


1H-NMR (600 MHz, CD2Cl2): δ = 0.39 (s, 6H), 0.74 (s, 6H), 1.11-1.23 (m, 7H), 1.32 (m, 3H),

1.42 (m, 4H) 1.56 (d, J = 15.27, 54H), 1.67 (m, 4H), 2.53 (d, J = 8.6 Hz, 2H), 5.10 (d, JP-H =

431.2 Hz, PH), 6.33 (s, 1H), 6.59 (m, 1H), 6.70 (m, 2H) ppm.

11B-NMR (96 MHz, CD2Cl2): δ = -18.39 ppm.

13C{

1H}-NMR (76 MHz, CD2Cl2): δ = 14.2, 14.8, 21.5, 22.8, 28.6, 30.3, 33.7, 37.9 (d, J =

26.90 Hz, P-C), 50.1, 50.5, 51.1, 58.1, 124.1, 125.1, 128.5, 129.4, 142.9 ppm. The carbon

atoms bonded to boron atom and the quaternary carbon of C6F5 ring were not observed.

19F{

1H}-NMR (282 MHz, CD2Cl2): δ = -131.59 (m, 4F), -131.97 (m, 4F), -166.54 (t, JF-F =

20.26 Hz, 2F), -167.49 (t, JF-F = 20.30 Hz, 2F), -167.73 (m, 4 F), -167.91 (m, 4F) ppm.


31P{


89

5.3.1 General procedure for the catalytic hydrosilylation of imines

In a glovebox, a reaction vial with a stirring bar was charged with imine (0.5 mmol, 1.0

equiv.) and catalyst (0.02 mmol) dissolved in dry toluene (1 mL). Dimethylphenylsilane (0.55

mmol, 1.1 equiv.) was added to the solution and the reaction mixture was stirred for the

indicated period of time in a glove box at room temperature. The conversion of the substrate

was determined by 1H-NMR spectroscopy of the crude reaction mixture. The products were

purified by flash chromatography on silica gel using n-pentane/ethyl acetate (10:1) as the

eluent. The enantiomeric excess was determined either by HPLC methods using a chiral

stationary phase column (Chiralcel OD-H) or by GC methods (Chirasil-Dex CB).

5.3.2 General procedure for the catalytic hydrogenation of imines

Under an argon atmosphere, the imine (0.5 mmol), catalyst 16 (2.0 mol %), and 1 mL

anhydrous toluene were transferred to a stainless steel autoclave. The autoclave was purged

three times with hydrogen and finally pressurized to 25 bar. The reaction mixture was stirred

at 65 °C for the indicated period of time, and then hydrogen gas was released. The conversion

of the substrate was determined by 1H NMR spectroscopy of the crude reaction mixture. After

hydrolysis using distilled water, the product was purified by chromatography with

pentane/ethyl acetate (10/1). The enantiomeric excess was determined by HPLC using a chiral

stationary phase column (Chiralcel OD-H, and AD-H) or by GC (Chirasil-Dex CB).

5.3.3 Catalyst 16 recycling experiments procedure

Under an argon atmosphere, catalyst 16 (2.5 or 5 mol %), and 1 mL anhydrous toluene were

transferred to a stainless steel autoclave. The autoclave was purged three times with hydrogen

and finally pressurised to 25 bar. The reaction mixture was stirred at 65°C for 1 day, and then

hydrogen gas was released. 5 mL of pentane were added and stirred until a colourless

precipitate was formed. The solvent was removed and the residue was washed with pentane (3

× 5 mL). The Imine was added to the catalyst and the procedure was repeated for the 3rd

, 4th

,

and 5th

cycles.

5.3.4 General procedure for the catalytic hydroboration of imines

In a glove box a reaction vial with stirring bar was charged with imine (0.5 mmol, 1.0 equiv.)

and catalyst (5 mol %), then dissolved in anhydrous degassed toluene or benzene (1 mL).

Pinacol or Catechol borane (0.54 mmol, 1.1 equiv.) was added to the solution and the reaction

mixture was stirred for the indicated period of time at room temperature. The conversion of

90

the substrate was determined by 1H-NMR spectroscopy of the crude reaction mixture. After

hydrolysis using distilled water, the product was purified by chromatography with

pentane/ethyl acetate (10/1). The enantiomeric excess was determined by HPLC using a chiral

stationary phase column (Chiralcel OD-H, and AD-H) or by GC (Chirasil-Dex CB).

5.3.5 Monitoring hydroboration reaction of imine 17 using PinBH as

hydroborating reagent

In a glove box a reaction vial with a stirring bar was charged with imine 17 (0.5 mmol, 1.0

equiv.) and catalyst (27, t-Bu3P) (5 mol %), then dissolved in anhydrous degassed benzene (1

mL). Pinacol borane (0.54 mmol, 1.1 equiv.) was added to the solution and the reaction

mixture was stirred for the indicated period of time in the glove box at room temperature. The

conversion of the substrate was monitored and determined by 1H-NMR spectroscopy of the

crude reaction mixture. After hydrolysis using distilled water, the product was purified by

chromatography with pentane/ethyl acetate (10/1). The enantiomeric excess was determined

by GC methods (Chirasil-Dex CB) 39 was obtained with 60 % ee after 24 hours.

92

5.3.6 Monitoring hydroboration reaction of imine 17 using CatBH as

hydroborating reagent

In a glove box a reaction vial with a stirring bar was charged with imine 17 (0.5 mmol, 1.0

equiv.) and catalyst (27, t-Bu3P) (5 mol %), then dissolved in dry degassed deuterated

benzene (1 mL). CatBH (0.54 mmol, 1.1 equiv.) was added to the solution and the reaction

mixture was stirred for the indicated period of time at room temperature. The conversion of

the substrate was monitored and determined by 1H-NMR spectroscopy of the crude reaction

mixture. After hydrolysis using distilled water, the product was purified by chromatography

with pentane/ethyl acetate (10/1). The enantiomeric excess was determined either by GC

methods (Chirasil-Dex CB) and 39 was obtained with 78 % ee after 1 hour.

94

5.3.7 Monitoring hydroboration reaction of imine 17 using CatBH with catalyst

3 and excess amount of t-Bu3P (cat.3 : t-Bu3P / 1:4)

In a glove box a reaction vial with a stirring bar was charged with the imine 17 (0.5 mmol, 1.0

equiv.) catalyst 3, (5 mol %) and excess t-Bu3P (0.1 mmol, 4 equiv.), then dissolved in dry

degassed deuterated benzene (1 mL). CatBH (0.54 mmol, 1.1 equiv.) was added to the

solution and the reaction mixture was stirred for the indicated period of time at room

temperature. The conversion of the substrate was monitored and determined by 1H-NMR

spectroscopy of the crude reaction mixture. After hydrolysis using distilled water, the product

was purified by flash chromatography on silica gel using n-pentane/ethyl acetate (10:1) as the

eluent. The enantiomeric excess was determined by GC methods (Chirasil-Dex CB) and 39

was obtained with only 15 % ee after one hour.

95

5.3.8 Hydroboration of imine 17 using CatBH

In a glove box a reaction vial with a stirring bar was charged with the imine 17 (0.5 mmol, 1.0

equiv.), then dissolved in dry degassed deuterated toluene. CatBH (0.54 mmol, 1.1 equiv.)

was added to the solution and the reaction mixture was stirred for the indicated period of time

in the glove box at room temperature. The conversion of the substrate was monitored and

determined by 1H-NMR spectroscopy of the crude reaction mixture. After hydrolysis using

distilled water, the product was purified by chromatography with pentane/ethyl acetate (10/1).

The enantiomeric excess was determined by GC methods (Chirasil-Dex CB) 0 % ee after 15

hours.

96

5.3.9 Monitoring hydroboration reaction of imine 17 using CatBH with catalyst

27

In a glove box a reaction vial with a stirring bar was charged with imine (0.5 mmol, 1.0

equiv.) and catalyst 27 (5 mol %), then dissolved in dry degassed deuterated benzene (1 mL).

CatBH (0.54 mmol, 1.1 equiv.) was added to the solution and the reaction mixture was stirred

for the indicated period of time in the glove box at room temperature. The conversion of the

substrate was monitored and determined by 1H-NMR spectroscopy of the crude reaction

mixture. After hydrolysis using distilled water, the product was purified by chromatography

with pentane/ethyl acetate (10/1). The enantiomeric excess was determined by GC methods

(Chirasil-Dex CB), 39 was obtained with 38 % ee after 24 hours.

98

6. Appendix

6.1 Selected NMR spectra

1H NMR

99

13C NMR

19

F{H} NMR

100

31P{H} NMR

31P NMR

101

11B NMR

13C APT NMR

102

1H NMR

103

13C NMR

19F{H} NMR

104

31P NMR

31P{H} NMR

105

11B NMR

13C APT NMR

106

1H NMR

13C NMR

107

19F{H} NMR

13C APT NMR

108

1H NMR

13C NMR

109

19F{H} NMR

13C APT NMR

110

References

[1] G. N. Lewis, Valence and The Structure of Atoms and Molecules, Chemical Catalogue

Inc.: New York, 1923.

[2] J. N. Brönsted, Recl. Trav. Chim. Pays-Bas 1923, 42, 718-728.

[3] H. C. Brown, H. I. Schlesinger, S. Z. Cardon, J. Am. Chem. Soc. 1942, 64, 325-329.

[4] a) G. Wittig, A. Rückert, Liebigs Ann. Chem. 1950, 566, 101-113; b) H. C. Brown, B.

Kanner, J. Am. Chem. Soc. 1966, 88, 986-992; c) Tochtermann.W, Angew. Chem. Int.

Ed. 1966, 5, 351-371; d) R. Damico, C. D. Broaddus, J. Org. Chem. 1966, 31, 1607-

1612; e) S. Doring, G. Erker, R. Frohlich, O. Meyer, K. Bergander, Organometallics

1998, 17, 2183-2187.

[5] H. C. Brown, J. Chem. Soc. (Resumed) 1956, 1248-1268.

[6] R. Roesler, W. E. Piers, M. Parvez, J. Organomet. Chem. 2003, 680, 218-222.

[7] G. C. Welch, R. R. San Juan, J. D. Masuda, D. W. Stephan, Science 2006, 314, 1124-

1126.

[8] a) D. W. Stephan, G. Erker, Angew. Chem. Int. Ed. 2010, 49, 46-76; b) C. Jiang, D. W.

Stephan, Dalton Trans. 2013, 42, 630-637; c) T. Voss, T. Mahdi, E. Otten, R.

Fröhlich, G. Kehr, D. W. Stephan, G. Erker, Organometallics 2012, 31, 2367-2378; d)

D. W. Stephan, Chem. Commun. 2010, 46, 8526-8533.

[9] P. A. Chase, G. C. Welch, T. Jurca, D. W. Stephan, Angew. Chem. Int. Ed. 2007, 46,

8050-8053.

[10] G. C. Welch, D. W. Stephan, J. Am. Chem. Soc. 2007, 129, 1880-1881.

[11] a) P. A. Chase, T. Jurca, D. W. Stephan, Chem. Commun. 2008, 1701-1703; b) D.

Chen, J. Klankermayer, Chem. Commun. 2008, 2130-2131.

[12] P. A. Chase, A. L. Gille, T. M. Gilbert, D. W. Stephan, Dalton Trans. 2009, 7179-

7188.

[13] P. Spies, G. Erker, G. Kehr, K. Bergander, R. Frohlich, S. Grimme, D. W. Stephan,

Chem. Commun. 2007, 5072-5074.

[14] a) P. Spies, S. Schwendemann, S. Lange, G. Kehr, R. Froehlich, G. Erker, Angew.

Chem. Int. Ed. 2008, 47, 7543-7546; b) P. Spies, G. Kehr, K. Bergander, B.

Wibbeling, R. Frohlich, G. Erker, Dalton Trans. 2009, 1534-1541.

[15] L. Greb, P. Ona-Burgos, B. Schirmer, S. Grimme, D. W. Stephan, J. Paradies, Angew.

Chem. Int. Ed. 2012, 51, 10164-10168.

111

[16] K. Chernichenko, A. Madarasz, I. Papai, M. Nieger, M. Leskela, T. Repo, Nat. Chem.

2013, 5, 718-723.

[17] D. W. Stephan, S. Greenberg, T. W. Graham, P. Chase, J. J. Hastie, S. J. Geier, J. M.

Farrell, C. C. Brown, Z. M. Heiden, G. C. Welch, M. Ullrich, Inorg. Chem. 2011, 50,

12338-12348.

[18] a) V. Sumerin, F. Schulz, M. Atsumi, C. Wang, M. Nieger, M. Leskela, T. Repo, P.

Pyykko, B. Rieger, J. Am. Chem. Soc. 2008, 130, 14117-14119; b) V. Sumerin, K.

Chernichenko, M. Nieger, M. Leskela, B. Rieger, T. Repo, Adv. Synth. Catal. 2011,

353, 2093-2110.

[19] D. Chen, Y. Wang, J. Klankermayer, Angew. Chem. Int. Ed. 2010, 49, 9475-9478.

[20] D. Chen, V. Leich, F. Pan, J. Klankermayer, Chem. Eur. J. 2012, 18, 5184-5187.

[21] Y. Liu, H. Du, J. Am. Chem. Soc. 2013, 135, 6810-6813.

[22] a) C. M. Momming, S. Froemel, G. Kehr, R. Froehlich, S. Grimme, G. Erker, J. Am.

Chem. Soc. 2009, 131, 12280-12289; b) C. M. Mömming, E. Otten, G. Kehr, R.

Fröhlich, S. Grimme, D. W. Stephan, G. Erker, Angew. Chem. Int. Ed. 2009, 48, 6643-

6646; c) K. V. Axenov, C. M. Mömming, G. Kehr, R. Fröhlich, G. Erker, Chem. Eur.

J. 2010, 16, 14069-14073; dC. M. Momming, G. Kehr, B. Wibbeling, R. Frohlich, G.

Erker, Dalton Trans. 2010, 39, 7556-7564.

[23] V. Sumerin, K. Chernichenko, M. Nieger, M. Leskelä, B. Rieger, T. Repo, Adv. Synth.

Catal. 2011, 353, 2093-2110.

[24] J. Coxon, M. Hartshorn, A. Lewis, Aust. J. Chem. 1971, 24, 1017-1026.

[25] D. J. Parks, R. E. von H. Spence, W. E. Piers, Angew. Chem. Int. Ed. Engl. 1995, 34,

809-811.

[26] a) M. Ullrich, A. J. Lough, D. W. Stephan, J. Am. Chem. Soc. 2009, 131, 52-53; b) M.

Ullrich, A. J. Lough, D. W. Stephan, Organometallics 2010, 29, 3647-3654.

[27] D. Winkelhaus, B. Neumann, H. G. Stammler, N. W. Mitzel, Dalton Trans. 2012, 41,

8609-8614.

[28] a) G. W. Coates, A. R. Dunn, L. M. Henling, J. W. Ziller, E. B. Lobkovsky, R. H.

Grubbs, J. Am. Chem. Soc. 1998, 120, 3641-3649; b) D. J. Parks, W. E. Piers, M.

Parvez, R. Atencio, M. J. Zaworotko, Organometallics 1998, 17, 1369-1377.

[29] F. Schulz, V. Sumerin, M. Leskelae, T. Repo, B. Rieger, Dalton Trans. 2010, 39,

1920-1922.

[30] L. Jia, X. Yang, C. Stern, T. J. Marks, Organometallics 1994, 13, 3755-3757.

[31] D. J. Parks, W. E. Piers, G. P. A. Yap, Organometallics 1998, 17, 5492-5503.

112

[32] Warren E. Piers, Geoffrey J. Irvine, V. C. Williams, Eur. J. Inorg. Chem. 2000, 2000,

2131-2142.

[33] Z. Lu, H. Hausmann, S. Becker, H. A. Wegner, J. Am. Chem. Soc. 2015, 137, 5332-

5335.

[34] C. F. Jiang, O. Blacque, H. Berke, Chem. Commun. 2009, 5518-5520.

[35] S. Wei, H. Du, J. Am. Chem. Soc. 2014, 136, 12261-12264.

[36] G. Ghattas, D. Chen, F. Pan, J. Klankermayer, Dalton Trans. 2012, 41, 9026-9028.

[37] D. R. Chambers, T. Chivers, Proc. Chem. Soc. 1963, 208.

[38] W. E. Piers, in Adv. Organomet. Chem., Vol. 52, 2005, pp. 1-76.

[39] A. G. Massey, A. J. Park, J. Organomet. Chem. 1964, 2, 245-250.

[40] X. Yang, C. L. Stern, T. J. Marks, J. Am. Chem. Soc. 1991, 113, 3623-3625.

[41] D. J. Parks, W. E. Piers, Tetrahedron 1998, 54, 15469-15488.

[42] a) R. E. v. H. Spence, W. E. Piers, Organometallics 1995, 14, 4617-4624; b) W. E.

Piers, T. Chivers, Chem. Soc. Rev. 1997, 26, 345-354.

[43] a) S. Wei, H. Du, J. Am. Chem. Soc. 2014, 136, 12261-12264; b) M. M. Morgan, A. J.

V. Marwitz, W. E. Piers, M. Parvez, Organometallics 2013, 32, 317-322; c) A. Y.

Houghton, J. Hurmalainen, A. Mansikkamäki, W. E. Piers, H. M. Tuononen, Nat.

Chem. 2014, 6, 983-988.

[44] M. Weidenbruch, N. Wessal, Chem. Ber. 1972, 105, 173-187.

[45] M. Hoshi, K. Shirakawa, M. Okimoto, Tetrahedron Lett. 2007, 48, 8475-8478.

[46] A.-M. Fuller, D. L. Hughes, S. J. Lancaster, C. M. White, Organometallics 2010, 29,

2194-2197.

[47] A. Schnurr, K. Samigullin, J. M. Breunig, M. Bolte, H.-W. Lerner, M. Wagner,

Organometallics 2011, 30, 2838-2843.

[48] R. Duchateau, S. J. Lancaster, M. Thornton-Pett, M. Bochmann, Organometallics

1997, 16, 4995-5005.

[49] S. Kobayashi, H. Ishitani, Chem. Rev. 1999, 99, 1069-1094.

[50] a) S. Vastag, J. Bakos, S. Tórös, N. E. Takach, R. Bruce King, B. Heil, L. Markó, J.

Mol. Catal. 1984, 22, 283-287; b) J. Bakos, I. Tóth, B. Heil, L. Markó, J. Organomet.

Chem. 1985, 279, 23-29; c) G.-J. Kang, W. R. Cullen, M. D. Fryzuk, B. R. James, J. P.

Kutney, J. Chem. Soc., Chem. Commun. 1988, 1466-1467; d) M. J. Burk, J. P.

Martinez, J. E. Feaster, N. Cosford, Tetrahedron 1994, 50, 4399-4428; e) A. G.

Becalski, W. R. Cullen, M. D. Fryzuk, B. R. James, G. J. Kang, S. J. Rettig, Inorg.

113

Chem. 1991, 30, 5002-5008; fH. Brunner, J. Bügler, B. Nuber, Tetrahedron:

Asymmetry 1996, 7, 3095-3098.

[51] a) F. Spindler, B. Pugin, H.-U. Blaser, Angew. Chem. Int. Ed. 1990, 29, 558-559; b) Y.

N. C. Chan, D. Meyer, J. A. Osborn, J. Chem. Soc., Chem. Commun. 1990, 869-871;

c) K. Tani, J.-i. Onouchi, T. Yamagata, Y. Kataoka, Chem. Lett. 1995, 24, 955-956; d)

Y. Ng Cheong Chan, J. A. Osborn, J. Am. Chem. Soc. 1990, 112, 9400-9401.

[52] W. Oppolzer, M. Wills, C. Starkemann, G. Bernardinelli, Tetrahedron Lett. 1990, 31,

4117-4120.

[53] a) C. A. Willoughby, S. L. Buchwald, J. Am. Chem. Soc. 1992, 114, 7562-7564; b) C.

A. Willoughby, S. L. Buchwald, J. Org. Chem. 1993, 58, 7627-7629; c) C. A.

Willoughby, S. L. Buchwald, J. Am. Chem. Soc. 1994, 116, 8952-8965.

[54] J. M. Blackwell, E. R. Sonmor, T. Scoccitti, W. E. Piers, Org. Lett. 2000, 2, 3921-

3923.

[55] M. Alcarazo, C. Gomez, S. Holle, R. Goddard, Angew. Chem. Int. Ed. 2010, 49, 5788-

5791.

[56] a) I. Beletskaya, A. Pelter, Tetrahedron 1997, 53, 4957-5026; b) K. Burgess, M. J.

Ohlmeyer, Chem. Rev. 1991, 91, 1179-1191.

[57] a) E. Fernandez, K. Maeda, M. W. Hooper, J. M. Brown, Chem. Eur. J. 2000, 6, 1840-

1846; b) Cathleen M. Crudden, D. Edwards, Eur. J. Org. Chem. 2003, 2003, 4695-

4712; c) M. V. Rangaishenvi, B. Singaram, H. C. Brown, J. Org. Chem. 1991, 56,

3286-3294; d) H. C. Brown, K. W. Kim, T. E. Cole, B. Singaram, J. Am. Chem. Soc.

1986, 108, 6761-6764; e) T. Hayashi, Y. Matsumoto, Y. Ito, J. Am. Chem. Soc. 1989,

111, 3426-3428.

[58] C. J. Lata, C. M. Crudden, J. Am. Chem. Soc. 2010, 132, 131-137.

[59] M. A. Dureen, A. Lough, T. M. Gilbert, D. W. Stephan, Chem. Commun. 2008, 4303-

4305.

[60] P. Eisenberger, A. M. Bailey, C. M. Crudden, J. Am. Chem. Soc. 2012, 134, 17384-

17387.

[61] C. F. Lane, G. W. Kabalka, Tetrahedron 1976, 32, 981-990.

[62] J. Hermeke, M. Mewald, M. Oestreich, J. Am. Chem. Soc. 2013, 135, 17537-17546.

[63] G. M. Sheldrick, University of Göttingen, 1996.

[64] G. M. Sheldrick, Acta Crystallogr., Sect. A: Found. Crystallogr. 2008, 64, 112-122.

[65] H. D. Flack, Acta Crystallogr., Sect. A: Found. Crystallogr. 1983, 39, 876-881.

114

[66] T. Bunlaksananusorn, A. Pérez Luna, M. Bonin, L. Micouin, P. Knochel, Synlett 2003,

2003, 2240-2242.

[67] T. Bunlaksananusorn, K. Polborn, P. Knochel, Angew. Chem. Int. Ed. 2003, 42, 3941-

3943.

115

Curriculum Vitae

Name: Ghazi Ghattas

Date of birth (place): 18 February 1985 (Barja, Lebanon)

Nationality: Lebanese

Current address: Vaalser straße 302, 52074 Aachen, Germany

Education:

Since Oct. 2010 Ph.D. in Chemistry

RWTH Aachen University, Aachen (Germany)

Institute of Technical and Macromolecular Chemistry

Group of Prof. Dr. Jürgen Klankermayer

Thesis: Frustrated Lewis Pair Catalysts for Asymmetric Hydrogenation,

Hydrosilylation and Hydroboration Reactions

Oct. 2009 – Sep. 2010 Masters in Chemistry

Rennes 1 University, Rennes (France)

Department of Chemistry, Organic Chemistry

Group of Dr. Christian Bruneau

Thesis: Synthesis of New Ruthenium Catalyst for Olefin Metathesis

Sep. 2003 – Oct. 2007 Applied Biochemistry, Maitrise in Science

Lebanese University, Beirut (Lebanon)

Department of Chemistry

Thesis: Anabolic Androgenic Steroids Actions and Effects

Frustrated Lewis Pair Catalysts for Asymmetric ...

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