Quantum Chemistry Studies On The Direct Aldol Reactions Between Acetone And Aldehydes Catalyzed By Proline And It Derivatives

Ab initio (HF) and density functional theory (B3LYP) were employed to study the direct aldol reactions between acetone and 2,2-dimethyl-propionaldehyde or 4-nitrobenz -aldehyde catalyzed by (S)-proline or it's (4)-hydroxyl derivatives, or (L,L)-proline peptides.The relative stabilities of R and S transition states formed in the stereocontrolling step reasonably explain the stereoselectivity of the reactions. That is the stereoselectivity of the aliphatic aldehydes possess better stereoselectivity than aromatic aldehydes, (L,L)-proline peptides gives worse stereoselectivities than (S)-proline dose, and (S)-(4)-hydroxyl prline possess good stereoselectivity.For the stereocontrolling step, four reactive channels corresponding to the syn and anti arrangement of the active methylene of enamine relative to the carboxylic acid group of (S)-proline and the two diastereoisomeric approach modes to the re and si of the carbonyl group of the aldehyde were studied. The compted results support and reinforce the List et. al proposed enamine mechanism.