BF3-Mediated cis-Selective Cycloaddition of O-Silyloxime with Alkenes

J Org Chem. 2015 May 1;80(9):4797-802. doi: 10.1021/acs.joc.5b00426. Epub 2015 Apr 22.

Abstract

A C-amide-substituted O-silylated oxime, (E)-(tert-butyldimethylsiloxyimino)acetic acid N,N-dimethylamide (8b), on treatment with 2.2 equiv of BF3·OEt2, in situ generated boracyclic nitrone-type intermediate BF3·14, which underwent cycloaddition with alkenes to give 3,5-cis-isoxazolidines as the major products. The mechanism was strongly supported by isolation of the reaction intermediate 14 that was characterized by X-ray diffraction and its further reaction. This cycloaddition was successfully applied to the synthesis of syn-HPA-12 known as an inhibitor of CERT that mediates the transport of ceramide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkenes / chemistry*
  • Amides / chemical synthesis*
  • Amides / chemistry
  • Boranes / chemistry*
  • Crystallography, X-Ray
  • Cyclization
  • Models, Molecular
  • Molecular Structure
  • Oximes / chemistry*
  • Silanes / chemistry*
  • Stereoisomerism

Substances

  • Alkenes
  • Amides
  • Boranes
  • N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl)dodecanamide
  • Oximes
  • Silanes
  • boron trifluoride