Enantioselective Michael addition of alpha-substituted cyanoacetates to vinyl ketones catalyzed by bifunctional organocatalysts

Chemistry. 2007;13(1):319-27. doi: 10.1002/chem.200600796.

Abstract

A highly enantioselective Michael addition of alpha-substituted cyanoacetates to vinyl ketones was accomplished in the presence of simple bifunctional thiourea/tertiary amine organocatalysts. A number of alpha-aryl or alkyl cyanoacetates have been successfully applied to give multifunctional compounds with an all-carbon-substituted quaternary stereocenter in excellent enantioselectivities (82-97 % ee) and yields (61-99 %). The optical pure adducts could be smoothly converted to variously structured beta(2,2)-amino acid esters. Moreover, an interesting reaction model involving multiple hydrogen-bonding interactions amongst the thiourea/tertiary amine catalyst and the reactants has been proposed based on the absolute configuration of the adduct and computational studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / chemistry*
  • Amino Acids / chemistry
  • Catalysis
  • Crystallography, X-Ray
  • Cyanides / chemistry*
  • Electrons
  • Ketones / chemistry*
  • Models, Molecular
  • Molecular Structure
  • Stereoisomerism

Substances

  • Acetates
  • Amino Acids
  • Cyanides
  • Ketones