Ritesh A. Annadate, Moorthy N. V. G. and Sunil V. Pansare* Pages 66 - 73 ( 8 )
Background: The catalytic asymmetric Michael addition of carbonyl compounds to nitrostyrenes is of interest because the reaction establishes two adjacent stereocenters in one step and the product γ-nitrocarbonyl compounds are synthetically useful intermediates. This reaction has been exhaustively investigated with β-nitrostyrenes as the Michael acceptors but the use of α-nitrostyrenes, for establishing nonadjacent stereocenters in the product, is not well studied.
Objective: The aim of this study was to investigate the organocatalytic asymmetric, enamine mediated, Michael addition of cyclic ketones and α,α-disubstituted aldehydes to in situ generated α- nitrostyrenes and to optimize the diastereoselectivity and the enantioselectivity of the reaction.
Method: The Michael addition reactions of a series of ketones and aldehydes with a variety of α- nitrostyrenes, that were generated in situ form nitroacetates, were conducted in a selection of solvents in the presence of chiral pyrrolidine catalysts and protic acid additives. Conditions that provided the highest asymmetric induction were identified.
Results: Under optimized conditions, γ-nitroketones (up to 99% ee) and γ-nitroaldehydes (up to 79% ee) were obtained. The synthetic utility of the γ-nitroladehydes was demonstrated by converting a representative Michael adduct into a functionalized pyrrolidine.
Conclusion: The enamine mediated Michael addition of cyclic ketones and α,α-disubstituted aldehydes to in situ generated α-nitrostyrenes proceeds with moderate to good levels of 1,3-asymmetric induction. The methodology complements the well-known Michael addition reactions of β- nitrostyrene, and provides access to enantiomerically enriched γ-aryl-γ-nitro ketones and γ-aryl-γ-nitro aldehydes.
Aldehydes, ketones, Michael addition, organocatalysis, α-nitrostyrene, carbonyl compounds.
Department of Chemistry, Memorial University, St. John`s, NL, A1B 3X7, Department of Chemistry, Memorial University, St. John`s, NL, A1B 3X7, Department of Chemistry, Memorial University, St. John`s, NL, A1B 3X7