Rapid fluorescent screening for bifunctional amine-acid catalysts: Efficient syntheses of quaternary carbon-containing aldols under organocatalysis

Direct catalytic aldol reactions of alpha,alpha-dialkylaldehyde donors and arylaldehyde acceptors have been performed using pyrrolidine-acetic acid bifunctional catalysts. This general and practical amine-acid combination was identified by screening catalysts using a new fluorescent detection system for carbon-carbon bond formation. Using 0.05 equiv of pyrrolidine and 0.25 equiv of acetic acid as catalyst, we obtained alpha,alpha-dialkylaldol product in 96% yield after 2 h at ambient temperature. Proline was a poor catalyst of this reaction.