Kinetic Resolution of 2-Aryl-4-methylenepiperidines toward Enantioenriched Functionalizable Piperidine Fragments

J Org Chem. 2022 Jul 1;87(13):8819-8823. doi: 10.1021/acs.joc.2c00862. Epub 2022 Jun 14.

Abstract

The base n-BuLi with sparteine allows a kinetic resolution of N-Boc-2-aryl-4-methylenepiperidines. The 2,2-disubstituted products and recovered starting materials were isolated with high enantiomeric ratios. From VT-NMR spectroscopy and DFT studies, the rate of rotation of the N-Boc group is fast. Lithiation and trapping of the enantioenriched starting materials gave 2,2-disubstituted piperidines with retention of stereochemistry. Functionalization of the 4-methylene group led to a variety of 2,4-disubstituted piperidines without loss of enantiopurity that could be useful building blocks for drug discovery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Piperidines / chemistry
  • Sparteine* / chemistry
  • Stereoisomerism

Substances

  • Piperidines
  • Sparteine