From Propargylic Alcohols to Substituted Thiochromenes: gem-Disubstituent Effect in Intramolecular Alkyne Iodo/hydroarylation

J Org Chem. 2021 May 21;86(10):7078-7091. doi: 10.1021/acs.joc.1c00333. Epub 2021 Apr 30.

Abstract

This work describes the 6-endo-dig cyclization of S-aryl propargyl sulfides to afford 2H-thiochromenes. The substitution at the propargylic position plays a crucial role in allowing intramolecular silver-catalyzed alkyne hydroarylation and N-iodosuccinimide-promoted iodoarylation. Additionally, a PTSA-catalyzed thiolation reaction of propargylic alcohols was developed to synthesize the required tertiary S-aryl propargyl ethers. The applicability of merging these two methods is demonstrated by synthesizing the retinoic acid receptor antagonist AGN194310.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes*
  • Catalysis
  • Cyclization
  • Iodine*
  • Molecular Structure

Substances

  • Alkynes
  • Iodine