A Selenourea-Thiourea Brønsted Acid Catalyst Facilitates Asymmetric Conjugate Additions of Amines to α,β-Unsaturated Esters

J Am Chem Soc. 2020 Mar 25;142(12):5627-5635. doi: 10.1021/jacs.9b12457. Epub 2020 Mar 11.

Abstract

β-Amino esters are obtained with high levels of enantioselectivity via the conjugate addition of cyclic amines to unactivated α,β-unsaturated esters. A related strategy enables the kinetic resolution of racemic cyclic 2-arylamines, using benzyl acrylate as the resolving agent. Reactions are facilitated by an unprecedented selenourea-thiourea organocatalyst. As elucidated by DFT calculations and 13C kinetic isotope effect studies, the rate-limiting and enantiodetermining step of the reaction is the protonation of a zwitterionic intermediate by the catalyst. This represents a rare case in which a thiourea compound functions as an asymmetric Brønsted acid catalyst.

Publication types

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

MeSH terms

  • Amines / chemical synthesis
  • Amines / chemistry*
  • Catalysis
  • Density Functional Theory
  • Esters / chemical synthesis
  • Esters / chemistry*
  • Kinetics
  • Models, Chemical
  • Organoselenium Compounds / chemistry*
  • Thiourea / chemistry*
  • Urea / analogs & derivatives*
  • Urea / chemistry

Substances

  • Amines
  • Esters
  • Organoselenium Compounds
  • selenourea
  • Urea
  • Thiourea