For the mechanism, reaction of pyrrolidine with the carbonyl donor can give enamine a that could proceed reaction with the re -face of the aldehydes to give the iminium ion b (Scheme 6). The latter can undergo hydrolysis to afford chiral β-hydroxyketone. The proposed transition state illustrates that enamine attack occurs on the re -face of the aldehyde d and e. This facial selectivity of attack by the enamine is dictated by minimizing steric interactions between the aldehyde substituent and the enamine substituent. The attack of the enamine on the si -face of the aldehyde leads to the unfavorable transition state c .

Scheme 6. Mechanism for Proline Catalyzed Aldol Reaction

10.1.2 Mannich Reaction

Parallel to the aldol reaction, enantioselective Mannich reaction of aldehyde, acetone and p -anisidine as the substrates has been explored with 50% yield and 94% ee (Scheme 7).

Scheme 7. L-Proline-Promoted One-Pot Three-Component Mannich-Type Reaction

The mechanism is analogous to that of the aldol reactions (Scheme 8). The reaction of proline with aldehyde or ketone can give enamine that could undergo reaction with the imine to form new stereocenters as iminium product. The latter on hydrolysis can give the target Mannich product. The reaction of ( E )-aldimine with the enamine on its si -face can give the syn product. Because of the re -face is blocked by steric interactions between the aromatic ring of the p -methoxyphenyl group and the ring of proline.

Scheme 8. Proposed Transition States and Products for the Mannich Reactions