Diastereoselective synthesis of tetrahydrofurans via mead reductive cyclization of keto-beta-lactones derived from the tandem Mukaiyama aldol lactonization (TMAL) process

J Org Chem. 2007 Nov 23;72(24):9053-9. doi: 10.1021/jo7014246. Epub 2007 Nov 1.

Abstract

The development of a diastereoselective, three-step strategy for the construction of substituted tetrahydrofurans from alkenyl aldehydes based on the tandem Mukaiyama aldol-lactonization process and Mead reductive cyclization of keto beta-lactones is reported. Stereochemical outcomes of the TMAL process are consistent with models established for Lewis acid-mediated additions to alpha-benzyloxy and beta-silyloxy aldehydes while reductions of the five-membered oxocarbenium ions are consistent with Woerpel's models. Further rationalization for observed high diastereoselectivity in reductions of alpha-silyloxy 5-membered oxocarbenium ions based on stereoelectronic effects are posited. A diagnostic trend for coupling constants of gamma-benzyloxy beta-lactones was observed that should enable assignment of the relative configuration of these systems.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / chemistry*
  • Alkenes / chemistry
  • Cyclization
  • Furans / chemical synthesis*
  • Lactones / chemistry*
  • Models, Chemical
  • Stereoisomerism

Substances

  • Aldehydes
  • Alkenes
  • Furans
  • Lactones
  • 3-hydroxybutanal