The Direct, Enantioselective, One-Pot, Three-Component, Cross-Mannich Reaction of Aldehydes: The Reason for the Higher Reactivity of Aldimineversus Aldehyde in Proline-Mediated Mannich and Aldol Reactions

In the proline-mediated Mannich and aldol reactions of propanal as a nucleophile, the aldimine prepared from benzaldehyde and p-anisidine is about 7 times more reactive than the corresponding alde- hyde, benzaldehyde, as an electrophile. This higher reactivity of aldimine over aldehyde is attributed to the carboxylic acid of proline protonating the basic ni- trogen atom of the aldimine more effectively than the oxygen atom of the aldehyde, an explanation which has been both experimentally and theoretically veri- fied.