Inversion of Enantioselectivity in Proline Catalysis by Basic Additives

Significance

A study towards the influence of base additives in the secondary amine catalyzed α-amination of aldehydes is presented. In these experiments DBU proved to have a crucial role on the stereochemical outcome of the transformation. Whereas the reaction without additives furnished the corresponding products with (R)-configuration and high enantioselectivity, the addition of DBU inverts the new stereocenter, albeit resulting in only moderate optical purity. A mechanistic rationale, involving interactions of the base with the carboxylate catalyst moiety, is provided.