Rapid Synthesis of α-Chiral Piperidines via a Highly Diastereoselective Continuous Flow Protocol

Org Lett. 2022 May 6;24(17):3205-3210. doi: 10.1021/acs.orglett.2c00975. Epub 2022 Apr 22.

Abstract

A practical continuous flow protocol has been developed using readily accessible N-(tert-butylsulfinyl)-bromoimine and Grignard reagents, providing various functionalized piperidines (34 examples) in superior results (typically >80% yield and with >90:10 dr) within minutes. The high-performance scale-up is smoothly carried out, and efficient synthesis of the drug precursor further showcases its utility. This flow process offers rapid and scalable access to enantioenriched α-substituted piperidines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Indicators and Reagents
  • Piperidines*
  • Stereoisomerism

Substances

  • Indicators and Reagents
  • Piperidines