Catalytic enantioselective cross-couplings of secondary alkyl electrophiles with secondary alkylmetal nucleophiles: Negishi reactions of racemic benzylic bromides with achiral alkylzinc reagents

J Am Chem Soc. 2012 Oct 17;134(41):17003-6. doi: 10.1021/ja308460z. Epub 2012 Oct 5.

Abstract

We have developed a nickel-catalyzed method for the asymmetric cross-coupling of secondary electrophiles with secondary nucleophiles, specifically, stereoconvergent Negishi reactions of racemic benzylic bromides with achiral cycloalkylzinc reagents. In contrast to most previous studies of enantioselective Negishi cross-couplings, tridentate pybox ligands are ineffective in this process; however, a new, readily available bidentate isoquinoline-oxazoline ligand furnishes excellent ee's and good yields. The use of acyclic alkylzinc reagents as coupling partners led to the discovery of a highly unusual isomerization that generates a significant quantity of a branched cross-coupling product from an unbranched nucleophile.

Publication types

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

MeSH terms

  • Catalysis
  • Hydrocarbons, Brominated / chemistry*
  • Isoquinolines / chemical synthesis*
  • Isoquinolines / chemistry
  • Molecular Structure
  • Nickel / chemistry*
  • Organometallic Compounds / chemistry*
  • Oxazoles / chemical synthesis*
  • Oxazoles / chemistry
  • Stereoisomerism
  • Zinc / chemistry*

Substances

  • Hydrocarbons, Brominated
  • Isoquinolines
  • Organometallic Compounds
  • Oxazoles
  • Nickel
  • Zinc
  • isoquinoline