Enantioconvergent Cross-Couplings of Racemic Alkylmetal Reagents With Unactivated Secondary Alkyl Electrophiles: Catalytic Asymmetric Negishi α-alkylations of N-Boc-pyrrolidine

J Am Chem Soc. 2013 Jul 31;135(30):10946-9. doi: 10.1021/ja4054114. Epub 2013 Jul 19.

Abstract

Although enantioconvergent alkyl-alkyl couplings of racemic electrophiles have been developed, there have been no reports of the corresponding reactions of racemic nucleophiles. Herein we describe Negishi cross-couplings of racemic α-zincated N-Boc-pyrrolidine with unactivated secondary halides, thus providing a one-pot, catalytic asymmetric method for the synthesis of a range of 2-alkylpyrrolidines (an important family of target molecules) from N-Boc-pyrrolidine, a commercially available precursor. Preliminary mechanistic studies indicated that two of the most straightforward mechanisms for enantioconvergence (dynamic kinetic resolution of the organometallic coupling partner and a simple β-hydride elimination/β-migratory insertion pathway) are unlikely to be operative.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alkylation
  • Catalysis
  • Indicators and Reagents / chemistry
  • Organometallic Compounds / chemistry*
  • Pyrrolidines / chemistry*
  • Stereoisomerism

Substances

  • Indicators and Reagents
  • Organometallic Compounds
  • Pyrrolidines
  • pyrrolidine