Regioselective, Diastereoselective, and Enantioselective One-Pot Tandem Reaction Based on an in Situ Formed Reductant: Preparation of 2,3-Disubstituted 1,5-Benzodiazepine

J Org Chem. 2021 Apr 2;86(7):5110-5119. doi: 10.1021/acs.joc.0c03064. Epub 2021 Mar 16.

Abstract

The 1,5-benzodiazepines are important skeletons frequently contained in medicinal chemistry. Herein, we described an unexpected tandem cyclization/transfer hydrogenation reaction for obtaining chiral 2,3-disubstituted 1,5-benzodiazepines. The enolizable aryl aldehydes were chosen as substrates to react with symmetric and unsymmetric o-phenylenediamines. The unforeseen tandem reaction occurred among many possible latent side reactions under chiral phosphoric acid catalysis and affords the corresponding products in moderate yields and regioselectivities, good diastereoselectivities, and enantiomeric ratio (up to 99:1).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzodiazepines*
  • Catalysis
  • Cyclization
  • Reducing Agents*
  • Stereoisomerism

Substances

  • Reducing Agents
  • Benzodiazepines