Alkylation and aldol reactions of acyl derivatives of N-1-(1 '-naphthyl)ethyl-O-tert-butylhydroxylamine: asymmetric synthesis of alpha-alkoxy-, alpha-substituted-beta-alkoxy- and alpha,beta-dialkoxyaldehydes

Alexander N. Chernega, Stephen G. Davies, Ai M. Fletcher, Christopher J. Goodwin, David Hepworth, R. Shyam Prasad, Paul M. Roberts, Edward D. Savory, Andrew D. Smith, James E. Thomson

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

Treatment of a range of O-protected glycolate derivatives of the chiral auxiliary N-1-(1'-naphthyl)ethyl-O-tert-butylhydroxylamine with KHMDS in the presence of 18-crown-6 followed by addition of an alkyl halide generates alpha-substituted derivatives with very high levels of diastereoselectivity. Alternatively, reaction of the potassium enolate of a propanoate or O-protected glycolate derivative of N-1-(1'-naphthyl)ethyl-O-tert-butylhydroxylamine with a range of aldehydes gives syn-aldol products with high levels of diastereoselectivity. These adducts may be reductively cleaved with LiAlH4 to give enantiopure alpha-alkoxy-, alpha-substituted-beta-alkoxy- and alpha,beta-dialkoxyaldehydes in good yield. (C) 2010 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)4167-4194
Number of pages28
JournalTetrahedron
Volume66
Issue number23
DOIs
Publication statusPublished - 5 Jun 2010

Keywords

  • Weinreb amide
  • Glycolate enolate
  • Diastereoselective alkylation
  • Aldol reaction
  • ACYCLIC STEREOSELECTION
  • SUPERQUAT ENAMIDES
  • CARBONYL-COMPOUNDS
  • GRIGNARD-REAGENTS
  • CARBOXYLIC-ACIDS
  • STERIC COURSE
  • ALLYL ETHERS
  • ALDEHYDES
  • GLYCOLATE
  • ALCOHOLS

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