α-Lithiation-electrophile trapping of N-thiopivaloylazetidin-3-ol: stereoselective synthesis of 2-substituted 3-hydroxyazetidines

J Org Chem. 2013 Feb 1;78(3):1098-106. doi: 10.1021/jo3025225. Epub 2013 Jan 10.

Abstract

α-Lithiation of N-thiopivaloylazetidin-3-ol and subsequent electrophile trapping provides access to a range of 2-substituted 3-hydroxyazetidines with generally good trans-diastereoselectivity, aside from deuteration, which gives the cis-diastereoisomer. Deuterium labeling studies indicate that the initial α-deprotonation occurs preferentially, but not exclusively, in a trans-selective manner. These studies also suggest that the stereochemical outcome of the electrophile trapping depends on the electrophile used but is independent of which α-proton (cis or trans to the hydroxyl group) is initially removed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Azetidines / chemical synthesis*
  • Azetidines / chemistry*
  • Deuterium / chemistry*
  • Lithium / chemistry*
  • Molecular Structure
  • Protons
  • Stereoisomerism

Substances

  • Azetidines
  • N-thiopivaloylazetidin-3-ol
  • Protons
  • Lithium
  • Deuterium