Asymmetric synthesis of substituted 1-aminocyclopropane-1-carboxylic acids via diketopiperazine methodology

Elena Buñuel; Steven D Bull; Stephen G Davies; A Christopher Garner; Edward D Savory; Andrew D Smith; Richard J Vickers; David J Watkin

doi:10.1039/b303348a

Asymmetric synthesis of substituted 1-aminocyclopropane-1-carboxylic acids via diketopiperazine methodology

Org Biomol Chem. 2003 Jul 21;1(14):2531-42. doi: 10.1039/b303348a.

Authors

Elena Buñuel¹, Steven D Bull, Stephen G Davies, A Christopher Garner, Edward D Savory, Andrew D Smith, Richard J Vickers, David J Watkin

Affiliation

¹ Dyson Perrins Laboratory, University of Oxford, South Parks Road, Oxford, UK OX1 3QY.

PMID: 12956073
DOI: 10.1039/b303348a

Abstract

Diketopiperazinespirocyclopropane 12 is prepared in > 98% d.e. via the conjugate addition of a phosphorus ylide to (6S)-N,N'-bis(p-methoxybenzyl)-3-methylenepiperazine-2,5-dione 2. Deprotection and hydrolysis of adduct 12 and subsequent peptide coupling demonstrate the applicability of this methodology to the asymmetric synthesis of 1-aminocyclopropane-1-carboxylic acids for incorporation into novel peptides. A model for the high level of diastereofacial selectivity observed in the cyclopropanation reaction is presented. A highly selective asymmetric approach (> 98% d.e.) to (S)-[2,2-(2)H2]-1-aminocyclopropane-1-carboxylic acid 29 is also reported via a deuterated sulfur ylide addition to acceptor 2.