Scalable Regioselective and Stereoselective Synthesis of Functionalized (E)-4-Iodobut-3-en-1-ols: Gram-Scale Total Synthesis of Fungal Decanolides and Derivatives

J Org Chem. 2018 Jan 19;83(2):980-992. doi: 10.1021/acs.joc.7b02324. Epub 2018 Jan 8.

Abstract

A reliable protocol to synthesize both racemic and chiral (E)-4-iodobut-3-en-1-ols from aldehydes or epoxides, respectively, containing various aromatic and aliphatic substitutions has been established. The utility of these compounds was then demonstrated by providing access to known fungal decanolides as well as novel aromatic macrocycles. The protocol provided a gram-scale route to (-)-aspinolide A and (-)-5-epi-aspinolide A utilizing a catalytic Nozaki-Hiyama-Kishi reaction to close the macrolide in the final step in 65-84% yields.

Publication types

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

MeSH terms

  • Aldehydes / chemistry
  • Butanols / chemical synthesis*
  • Butanols / chemistry
  • Epoxy Compounds / chemistry
  • Lactones / chemical synthesis*
  • Lactones / chemistry
  • Macrocyclic Compounds / chemical synthesis*
  • Macrocyclic Compounds / chemistry
  • Molecular Structure
  • Stereoisomerism

Substances

  • Aldehydes
  • Butanols
  • Epoxy Compounds
  • Lactones
  • Macrocyclic Compounds
  • aspinolide B