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Synthesis 2010(21): 3693-3699  
DOI: 10.1055/s-0030-1258235
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of Adamantylglycine Using a Diastereoselective Grignard-to-Nitrone Addition

Alevtina Baskakova, Wolfgang Frey, Volker Jäger*
Universität Stuttgart, Institut für Organische Chemie, Pfaffenwaldring 55, 70569 Stuttgart, Germany
Fax: +49(711)68564321; e-Mail: jager.ioc@uni-stuttgart.de;
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Publication History

Received 11 June 2010
Publication Date:
30 August 2010 (online)

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Abstract

In contrast to amino acids with a bulky substituent like tert-leucine, adamantylglycine has so far received little attention. Here, a new, practical synthesis of adamantylglycine is described. This is based on a highly diastereoselective addition of adamantyl Grignard reagent to 2,3-O-cyclohexylideneglyceraldehyde N-benzylnitrone, mediated by the Lewis acid diethylaluminum chloride. Adamantylglycine is obtained from the nitrone in 6 steps and 28% yield as a crystalline hydrochloride with 0.5 methanol incorporated.

Key words

glyceraldehyde - chiral nitrone - Grignard addition - electrophilic glycine equivalent - crystal structure

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36

Crystallographic data for adamantylglycine 1˙HCl˙(0.5MeOH) have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication no. CCDC-770794. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: +44 (1223)336033 or e-mail: deposit@ccdc.cam.ac.uk].

37

The presence of MeOH in crystalline 1˙HCl has apparently been overlooked in earlier work.8,9