Asymmetric synthesis of 4-amino-gamma-butyrolactones via lithium amide conjugate addition

Elin Abraham, Jason W. B. Cooke, Stephen G. Davies, Alan Naylor, Rebecca L. Nicholson, Paul D. Price, Andrew D. Smith

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Upon treatment with homochiral lithium (R)-N-benzyl-N-(alpha-methylbenzyl) amide, gamma-benzyloxy but-2-enoates undergo competitive conjugate addition and gamma-deprotonation, while gamma-tert-butyldimethylsilyloxy but-2-enoates undergo exclusive conjugate addition. Treatment of g-benzyloxy or g-tert-butyldimethylsilyloxy but-2-enamides with lithium (R)-N-benzyl-N-(a-methylbenzyl) amide furnishes exclusively the gamma-benzyloxy-or gamma-tert-butyldimethylsilyloxy-beta-amino amide products of conjugate addition in high de. The gamma-tert-butyldimethylsilyloxy-beta-amino butanoate products of conjugate addition readily undergo O-desilylation and concomitant cyclisation to furnish 4-[N-benzyl-N-(alpha-methylbenzyl)amino]-gamma-butyrolactone, which may be stereoselectively functionalised via deprotonation and alkylation to give the corresponding trans-3-alkyl-4-amino-gamma-butyrolactones. Alternatively, stereoselective alkylation of gamma-benzyloxy-or gamma-tert-butyldimethylsilyloxy-beta- amino butanoates and butanamides through enolate formation and alkylation following a tandem (via the (Z)-lithium enolate) or stepwise (via the (E)-lithium enolate) protocol gives a range of separable syn- and anti-alpha-alkyl-beta-amino esters and amides. O-Silyl deprotection of the syn- and anti-alpha-alkyl-beta-amino butanoates with TBAF and concomitant cyclisation provide trans-3-alkyl-4-amino-gamma-butyrolactones, consistent with epimerisation to the thermodynamically favoured trans-lactone occurring upon deprotection. (C) 2007 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)5855-5872
Number of pages18
JournalTetrahedron
Volume63
Issue number26
DOIs
Publication statusPublished - 25 Jun 2007

Keywords

  • BETA-AMINO ACIDS
  • L-ASPARTIC ACID
  • STEREOSELECTIVE ROUTE
  • CYCLIZATION REACTION
  • SIDE-CHAINS
  • DERIVATIVES
  • EQUIVALENTS
  • ESTERS
  • (R)-N-BENZYL-N-ALPHA-METHYLBENZYLAMIDE
  • (-)-(1R,2S)-CISPENTACIN

Fingerprint

Dive into the research topics of 'Asymmetric synthesis of 4-amino-gamma-butyrolactones via lithium amide conjugate addition'. Together they form a unique fingerprint.

Cite this