Enantioselective Conjugate Addition of Malononitrile to Chalcones Promoted by α,α-L-Diaryl Prolinols: Noncovalent versus Covalent Catalysis?

The enantioselective conjugate addition of malononitrile to trans-chalcones has been investigated as a case study using easily available alpha,alpha-L-diaryl prolinols as promoters. Both experimental and computational results are consistent with a bifunctional noncovalent mode of activation of the reactive partners, provided by the secondary amine and hydroxyl groups of the promoter as general base and acid catalysis. This most energetically affordable pathway predicts predominant formation of the R-configured adducts, which is in agreement with the experimental findings. The present study addresses, for the first time, the ability of proline derivatives to assist product formation through noncovalent catalysis, in analogy to the mode of action typically recognized for Cinchona alkaloids.