Synthesis of 3-Aryl-3-Sulfanyl Azetidines by Iron-Catalyzed Thiol Alkylation with N-Cbz Azetidinols

J Org Chem. 2019 May 3;84(9):5943-5956. doi: 10.1021/acs.joc.9b00613. Epub 2019 Apr 19.

Abstract

New small-ring derivatives can provide valuable motifs in new chemical space for drug design. 3-Aryl-3-sulfanyl azetidines are synthesized directly from azetidine-3-ols in excellent yield by a mild Fe-catalyzed thiol alkylation. A broad range of thiols and azetidinols bearing electron-donating aromatics are successful, proceeding via an azetidine carbocation. The N-carboxybenzyl group is a requirement for good reactivity and enables the NH-azetidine to be revealed. Further reactions of the azetidine sulfides demonstrate their potential for incorporation in drug discovery programs.

Publication types

  • Research Support, Non-U.S. Gov't