Combining Chiral Aldehyde Catalysis and Transition-Metal Catalysis for Enantioselective α-Allylic Alkylation of Amino Acid Esters

J Am Chem Soc. 2019 Apr 3;141(13):5159-5163. doi: 10.1021/jacs.9b01910. Epub 2019 Mar 25.

Abstract

A chiral aldehyde is rationally combined with a Lewis acid and a transition metal for the first time to form a triple catalytic system. This cocatalytic system exhibits good catalytic activation and stereoselective-control abilities in the asymmetric α-allylation reaction of N-unprotected amino acid esters and allyl acetates. Optically active α,α-disubstituted α-amino acids (α-AAs) are generated in good yields (up to 87%) and enantioselectivities (up to 96% ee). Preliminary mechanism investigation indicates that the chiral aldehyde 3f acts both as an organocatalyst to activate the amino acid ester via the formation of a Schiff base, and as a ligand to facilitate the nucleophilic attack process by coordinating with π-allyl Pd(II) species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / chemistry*
  • Alkylation
  • Allyl Compounds / chemistry*
  • Amino Acids / chemical synthesis*
  • Amino Acids / chemistry
  • Catalysis
  • Esters / chemical synthesis*
  • Esters / chemistry
  • Molecular Structure
  • Organometallic Compounds / chemistry*
  • Stereoisomerism
  • Transition Elements / chemistry*

Substances

  • Aldehydes
  • Allyl Compounds
  • Amino Acids
  • Esters
  • Organometallic Compounds
  • Transition Elements