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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: [email protected] 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: [email protected]), on quoting the depository number CSD-408918.