Oxidative [2 + 1 + 1 + 1] Annulation of Aldehydes and Methylene Nitriles: Synthesis of Diastereoselective Polysubstituted Cyclopentenes

J Org Chem. 2022 Aug 5;87(15):10298-10308. doi: 10.1021/acs.joc.2c01330. Epub 2022 Jul 22.

Abstract

Herein, we report a green cascade approach to prepare a variety of diastereoselective polysubstituted cyclopentene derivatives through metal-free oxidative [2 + 1 + 1 + 1] annulation of aldehydes and methylene nitriles. Mechanistic studies demonstrated that the reaction underwent a four-step cascade reaction including air oxidation and Michael addition to obtain the final product. This reaction features readily available starting materials, transition metal-free, eco-friendly operations, gram-scale syntheses, and wide functional group tolerance. The methodology may be useful for the construction of polysubstituted cyano-cyclopentene heterocycles with potential biological activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes*
  • Cyclization
  • Cyclopentanes*
  • Nitriles
  • Oxidative Stress

Substances

  • Aldehydes
  • Cyclopentanes
  • Nitriles