Asymmetric synthesis of the stereoisomers of 2-amino-5-carboxymethyl-cyclopentane-1-carboxylate

Julio G. Urones, Narciso M. Garrido*, David Díez, Mohamed M. El Hammoumi, Sara H. Dominguez, J. Antonio Casaseca, Stephen G. Davies, Andrew D. Smith

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

The stereoisomers of 2-amino-5-carboxymethyl-cyclopentane-1-carboxylate may be prepared stereoselectively from diester derivatives of (E,E)-octa-2,6-diendioc acid, with the key step utilising the conjugate addition of homochiral lithium N-benzyl-N-α-methylbenzylamide. The trans-C(1)-C(2)-stereoisomers are readily prepared via a diastereoselective tandem conjugate addition cyclisation protocol with lithium (R)-N-benzyl-N-α-methylbenzylamide, with subsequent hydrogenolysis and ester hydrolysis giving the (1R,2R,5R)- and (1R,2R,5S)-β-amino diacids in good yields. The preparation of the cis-C(1)-C(2)-stereoisomers utilises a protocol involving N-oxidation and Cope elimination of the major diastereoisomeric product arising from conjugate addition and cyclisation, giving homochiral (R)-5-carboxymethyl-cyclopentene-1-carboxylate. Conjugate addition of either lithium (R)- or (S)-N-benzyl-N-α-methylbenzylamide to (R)-5-carboxymethyl-cyclopentene-1-carboxylate, and diastereoselective protonation with 2,6-di-tert-butyl phenol gives, after hydrogenolysis and ester hydrolysis, the (1S,2R,5R)- and (1R,2S,5R)-β-amino diacids in good yield. The use of (S)-N-benzyl-N-α-methylbenzylamide in the initial conjugate addition and cyclisation reaction, and subsequent repetition of the elimination and conjugate addition strategy allows stereoselective access to all stereoisomers of 2-amino-5-carboxymethyl-cyclopentane-1-carboxylate.

Original languageEnglish
Pages (from-to)364-372
Number of pages9
JournalOrganic and Biomolecular Chemistry
Volume2
Issue number3
DOIs
Publication statusPublished - 7 Feb 2004

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