Enantioselective, Copper-Catalyzed Alkynylation of Ketimines To Deliver Isoquinolines with α-Diaryl Tetrasubstituted Stereocenters

Org Lett. 2016 Dec 2;18(23):6006-6009. doi: 10.1021/acs.orglett.6b02787. Epub 2016 Nov 16.

Abstract

An enantioselective, copper-catalyzed alkynylation of cyclic α,α-diaryl ketiminium ions has been developed to deliver isoquinoline products with diaryl, tetrasubstituted stereocenters. The success of this reaction relied on identification of Ph-PyBox as the optimal ligand, i-Pr2NEt as the base, and CHCl3 as the solvent. A broad scope and functional group tolerance were observed. Notably, the use of both aryl and silyl acetylenes results in high yields and enantioselectivities. Mechanistic experiments are consistent with a dimeric or higher order catalyst.

Publication types

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

MeSH terms

  • Alkylation
  • Catalysis
  • Copper / chemistry*
  • Imines / chemistry*
  • Isoquinolines / chemical synthesis*
  • Isoquinolines / chemistry
  • Molecular Structure
  • Nitriles / chemistry*
  • Stereoisomerism

Substances

  • Imines
  • Isoquinolines
  • Nitriles
  • ketimine
  • Copper