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

Abstract

A highly enantioselective Michael addition of α-substituted cyanoacetates to vinyl ketones was accomplished in the presence of simple bifunctional thiourea/tertiary amine organocatalysts. A number of α-aryl or alkyl cyanoacetates have been successfully applied to give multifunctional compounds with an all-carbon-substi tuted quaternary Stereocenter in excellent enantioselectivities (82-97% ee) and yields (61-99%). The optical pure adducts could be smoothly converted to variously structured β2.2-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. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA.