Synthesis of C-4 Substituted Amido Nicotine Derivatives via Copper(I)- and (II)-Catalyzed Cross-Coupling Reactions

J Org Chem. 2016 Nov 18;81(22):11529-11534. doi: 10.1021/acs.joc.6b02319. Epub 2016 Nov 1.

Abstract

The syntheses of seven novel amido nicotine derivatives 12-18 from (S)-nicotine are presented. (S)-Nicotine and (S)-6-chloronicotine derivatives were cross-coupled with the corresponding amides 6-10 at the C-4 position of the pyridine ring via copper(I)-mediated reactions. Derivatives 16-18 were also obtained via copper(II)-mediated reactions from (S)-nicotine containing a C-4 boronic acid pinacol ester group. The optimization of reaction conditions for both routes provided a useful method for preparing C-4 amide-containing nicotine analogs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amides / chemistry*
  • Carbon-13 Magnetic Resonance Spectroscopy
  • Catalysis
  • Copper / chemistry*
  • Mass Spectrometry
  • Nicotine / chemical synthesis*
  • Nicotine / chemistry
  • Proton Magnetic Resonance Spectroscopy

Substances

  • Amides
  • Nicotine
  • Copper