Enantioselective Michael Addition to α,β-Unsaturated Aldehydes: Combinatorial Catalyst Preparation and Screening, Reaction Optimization, and Mechanistic Studies

Shortcut to chiral catalysts: An efficient combinatorial strategy based on back reaction screening by ESI-MS allows rapid evaluation of organocatalysts for the asymmetric Michael addition to α,β-unsaturated aldehydes (see scheme). An unexpected nonlinear effect has been observed in this reaction, resulting from a double nucleophilic–electrophilic activation mechanism involving two catalyst molecules.