ChemInform Abstract: Catalytic Enantioselective Direct Michael Additions of Ketones to Alkylidene Malonates

— Enantioselective direct Michael additions of ketones using ( S )-1-(2-pyrrolidinylmethyl)-pyrrolidine as a catalyst aredescribed. Michael adducts with up to 91% e.e. were obtained by the reaction of alkylidene malonates with simple unactivatedketones under mild reaction conditions. © 2001 Elsevier Science Ltd. All rights reserved. An increasing demand for optically active compoundshas stimulated the development of catalytic asymmetricbond-forming reactions. 1 Of the carbon carbon bondforming reactions, the enantioselective Michael reactionhas been one of the most studied in synthetic organicchemistry. 2 Typically, carbon nucleophiles that containan active methylene center such as malonic acid esters, -keto esters, nitroalkanes, etc. have been studied. 3 Ketones, however, while they are versatile carbonnucleophiles, have generally been used as donors onlyfollowing their pre-activation by conversion into highlyreactive enol or enamine equivalents. 4 In these cases,additional synthetic step(s), stoichiometric amounts ofbase, additional reagents (silylating agents to form theenol silyl ether or chiral amines to form the enaminederivative) or chiral ligands are required. A potentiallymore promising strategy would involve catalysis ofdirect additions of unmodified ketones to Michael-typeacceptors. The development of catalytic asymmetricvariants of this process would provide access to opti-cally enriched 1,5-dicarbonyl synthons.As part of our ongoing program directed towardsidentifying small organic molecules as catalysts ofasymmetric reactions, we explore here the direct addi-tion of ketones through an enamine-type mechanism toMichael-type acceptors. Chiral amines have been usedpreviously in catalytic asymmetric Michael additions