Oxetan-3-ols as 1,2-bis-Electrophiles in a Brønsted-Acid-Catalyzed Synthesis of 1,4-Dioxanes

Org Lett. 2022 Apr 1;24(12):2365-2370. doi: 10.1021/acs.orglett.2c00568. Epub 2022 Mar 21.

Abstract

Annulations that combine diacceptors with bis-nucleophiles are uncommon. Here, we report the synthesis of 1,4-dioxanes from 3-aryloxetan-3-ols, as 1,2-bis-electrophiles and 1,2-diols. Brønsted acid Tf2NH catalyzes both the selective activation of the oxetanol, to form an oxetane carbocation that reacts with the diol, and intramolecular ring opening of the oxetane. High regio- and diastereoselectivity are achieved with unsymmetrical diols. The substituted dioxanes and fused bicyclic products present interesting motifs for drug discovery and can be further functionalized.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohols*
  • Catalysis
  • Dioxanes*
  • Stereoisomerism

Substances

  • Alcohols
  • Dioxanes
  • 1,4-dioxane