The direct, enantioselective, one-pot, three-component, Cross-Mannich reaction of aldehydes:: The reason for the higher reactivity of aldimine versus 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 aldehyde, benzaldehyde, as an electrophile. This higher reactivity of aldimine over aldehyde is attributed to the carboxylic acid of proline protonating the basic nitrogen atom of the aldimine more effectively than the oxygen atom of the aldehyde, an explanation which has been both experimentally and theoretically verified.