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Synthesis and Crystal Structure of N-[(15,4/?)-2-Oxo-pinanyl]-/3-alanine MethylesterBarbara Albert3, Martin Jansen*b, Jörg Jakobic, Eberhard Steckhanc3 Institut für Anorganische Chemie, Rheinische Friedrich-Wilhelms-Universität Bonn,

Gerhard-Domagk-Str. 1. D-53121 Bonn. E-mail: albert@snchemie2.chemie.uni-bonn.de b Max-Planck-Institut für Festkörperforschung, Heisenbergstr. 1, D-70569 Stuttgart c Kekule-Institut für Organische Chemie und Biochemie,

Rheinische Friedrich-Wilhelms-Universität Bonn, Gerhard-Domagk-Str. 1, D-53121 Bonn

Z. Naturforsch. 53 b, 1188-1190 (1998); received April 17, 1998N-[( 1 S,4i?)-2-Oxo-pinanyl]-/3-alanineMethylester, Chiral /3-Alanine Equivalent, Crystal Struc­ture, Hydrogen Bond, Electrochemical Modification

The title compound, N-[(lS,4/?)-2-oxo-pinanyl]-/3-alanine methylester, is an important start­ing material for the electrochemical preparation of chiral amidoalkylation reagents in the syn­thesis of chiral /^-substituted /3-amino acid derivatives. The investigation of its crystal structure reveals an arrangement of the carbonyl group and the amine function, which is influenced by a hydrogen bonding interaction. This conformation makes the molecule especially appropriate for further synthetical modification.

Introduction

The development of new routes for the enantios­elective synthesis of /^-substituted /3-amino acids is considered to be important because these com­pounds are both interesting chiral, bifunctional sub­strates in organic syntheses and physiologically ac­tive substances [1], The title compound is a deriva­tive of ketopinic acid. This kind of compound is a useful chiral auxiliary in the asymmetric synthesis of chiral /3-alanine equivalents [2], especially if it is possible to introduce diastereoselectively a side chain in the 3'-position of the /3-alanine moiety of the molecule. To assess the value of this molecule as a chiral /3-alanine equivalent, it seemed highly de­sirable to elucidate its atomic arrangement by X-ray structure analysis.

Results and Discussion

N-[(15',4/?)-2-oxo-pinanyl]-/3-alanine methyl­ester was synthesised from camphorsulfonyl chlo­ride by oxidation to ketopinic acid and subse­quent reaction with /3-alanine methylester [1, 3-5] (Scheme 1).

Single crystals were grown by recrystallisa­tion from cyclohexane and investigated by X-ray

* Reprint requests to Prof. Dr. M. Jansen.

0932-0776/98/1000-1188 $ 06.00 (c) 1998 Verlag der Zeitschrift für Naturforschung. Tübingen • www.znaturforsch.com K

Scheme 1.

diffraction (Table I). The molecular structure is shown in Fig. 1 (see also the labelling scheme). The asymmetric unit contains one formula unit of the ti­tle compound. The six-membered ring shows the expected boat-conformation. Bond distances and angles have typical values (Table II). The most in­teresting feature of the crystal structure is an in­tramolecular hydrogen bond between the oxygen atom of the carbonyl group (02) and the N atom of the amine function (Nl). The position of the bridging H atom (HI) was localised in the differ­ence Fourier map. The N l - H l - 0 2 angle of 135° and the 02-H1 distance of 2.05 A are typical for this type of hydrogen bonding interaction [7]. It is therefore reasonable to describe the molecular sit­uation around the amine function as fairly rigid,

B. Albert et al. • Synthesis and Crystal Structure of N-[(lS,4/?)-2-Oxo-pinanyl]-/?-alanine Methylester 1189

Table I. Crystal and refinement data for N-[(lS,4/?)-2- oxo-pinanyl]-/3-alanine methylester.

Formula unit C14H21NO4Crystal system OrthorhombicSpace group P21212 1* (A) 10.196 (2)MA) 10.959 (2)c(A) 13.008 (3)V (A ) 1453.5 (5)Z 4Dcaic (Mg m-3) 1 .222Measured reflections 4603Independent reflections 2108Parameters 185Rim 0.0275H (mm-1) 0.0899 Range 0—>24h, k, I 0—̂ 11,-12—̂ 12,-1 4 —>14R(F)/wR(F2) 0.0438/0.1260S 0.960P m a x /P m in (eA ) 0.219/-0.162Extinction coefficient 0.070 (8)Flack parameter 0.1 (15)

Fig. 1. ORTEP diagram [6] of the title structure with 50% probability displacement ellipsoids. H atoms except HI are omitted for clarity. HI is shown with arbitrary radius.

the rotational freedom around the Cl-CIO bond be­ing reduced due to N-H-O interaction. This situa­tion should be retained also in the amidoalkylation

Table II. Selected bond distances and angleso in N- [(lS/U?)-2-oxo-pinanyl]-/3-alanine methylester (A/°).

010-C10 1.216(3) C12-C11 1.489(3)C12-C13 1.509(3) N1-C10 1.330(3)N l-C ll 1.459(3) Nl-Hl 0.91(3)0 2 -H 1 2.05(3)C 10 -N 1 -C 1 1 122.5(2) C10-N1-H1 118(2)010-C10-N1 1 2 1 .8(2 ) 010-C10-C1 121.3(2)

process via the intermediate N-acyliminium ion. Thus, the introduction of a nucleophile at C l l should take place predominately from the hindered Si-face resulting in the diastereoselective formation of the (^-product. This is, indeed, what is found in the amidoalkylation reaction after electrochemical methoxylation [1].

Experimental

The title compound was obtained by reaction of the acid chloride of ketopinic acid (made from (15,4/?)- ketopinic acid, 3.6 g, and SOCI2, 5 ml, refluxing for2 h) with ^-alanine methylester hydrochloride (2.76 g) and potassium carbonate (5 g) in chloroform (50 ml) at room temperature (yield 85%). Large, colourless crystals (columns) were grown by recrystallisation from cyclo- hexane; m.p. 51-53°C. The compound was characterised by 'H NMR, 13C NMR and infrared spectroscopy [1] as well as chemical analysis.C14H21NO4 (267.3):

Calcd C 62.90 H 7.92 N5.24% ,Found C 62.78 H 7.94 N5.55% .[a]D = +70.5 (c = 1.0, CHCI3). Data collection was

performed at room temperature (293(2) K) on an Enraf- Nonius CAD-4 diffractometer (MoKa radiation, lc - 29 scans). Cell parameters were determined from 24 reflec­tions (9 = 12.21 —► 22.48). The structure was solved by direct methods (SHELXS86 [8]) and refined on F2 us­ing the program SHELXL93 [9]. All H atoms except for HI were treated as riding atoms with C-H distances of 0.96 A [10],

[1] J. Jakobi, PhD thesis, Bonn (1995). [3] M. F. Halsanger, J. Heikes, Synthesis 801 (1981).[2] P. Brungs, K. Danielmeier, J. Jakobi, C. Nothhelfer, [4] W. C. M. C. Kokke, F. A. Varkevisser, J. Org. Chem.

A. Stahl, A. Zietlow, E. Steckhan, J. Chim. Phys. 93, 39, 1653 (1974).575 (1996).

1190 B. Albert et al. ■ Synthesis and Crystal Structure o f N-[( IS,4/?)-2-Oxo-pinanyl]-/3-alanine Methylester

[5] a) P. D. Bartlett, L. H. Knox, Org. Synth. Collect. Vol. V, 196 (1973);b) P. D. Bartlett, L. H. Knox, Org. Synth. Collect. Vol. V, 689 (1973).

[6] C. K. Johnson: ORTEPII. Report ORNL-5138. Oak Ridge National Laboratory, Tennessee, USA (1976).

[7] R. Taylor, O. Kennard, J. Am. Chem. Soc. 104,5063 (1982).

[8] G. M. Sheldrick, Acta Crystallogr. A46,467 (1990).

[9] G. M. Sheldrick: SHELXL93. Program for the refinement of Crystal Structures. University of Göttingen, Germany (1993).

[10] Further details of the crystal structure investi­gation may be obtained from the Fachinforma- tionszentrum Karlsruhe, D-76344 Eggenstein-Leo- poldshafen, Germany (fax: (+49)7247-808666; e- mail: crysdata@fiz-karlsruhe.de), on quoting the de­pository number CSD-408918.