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