Cooperative Pd/Cu-catalyzed diastereodivergent coupling of allenamides and aldimine esters to access the Mannich-type motifs

Abstract

Mannich reaction is a significant transformation to prepare chiral amines from imine; however, vinylimines are still unaddressed substrates in this transformation due to the inherent competition between the Mannich and Michael addition. Herein we report a cooperative Pd/Cu-catalyzed enantioselective coupling of allenamides with aldimine esters for expeditious access to Mannich-type motifs α,β-diamino esters. The reaction has excellent regioselectivity, and by selecting the combinations of Pd and Cu catalysts with appropriate chiralities, both the syn- and anti- coupling products could be selectively prepared with high enantio-, diastereoselectivities. This work represents a rare example of employing cooperative catalysis for achieving diastereodivergent Mannich-type coupling reaction and would inspire further studies in this field. • Formal Mannich reaction of vinylimines • Cooperative palladium/copper catalysis-enabled stereodivergent coupling • Access all four stereoisomers of α,β-diamino esters Mannich reaction is among the most useful methods in preparing chiral amine compounds. Despite the huge success in catalytic enantioselective Mannich reaction, diastereodivergent preparing both syn- and anti- Mannich products from the same set of substrates is still underdeveloped. On the other hand, due to the inherent regioselectivity issue (Mannich versus Michael addition), vinylimines are still less-solved challenging substrates in Mannich reaction. We report a cooperative Pd/Cu-catalyzed enantioselective coupling of allenamides with aldimine esters for access to Mannich-type motifs α,β-diamino esters. By choosing the appropriate combination of chiralities of Pd and Cu catalysts, diastereodivergent access to both the syn - and anti -coupling products could be achieved with good regio-, diastereo-, and enantioselectivities. This work sheds light on using cooperative catalysis to achieve Mannich-type motifs in a diastereodivergent manner. Zi et al. describe a cooperative Pd/Cu catalyst system for diastereodivergent coupling of allenamides with aldimine esters, which provides a formal Mannich-type reaction of vinylimines. By choosing the appropriate combination of chiralities of Pd and Cu catalysts, all four stereoisomers of α,β-diamino esters could be selectively achieved with high enantio- and diastereoselectivities.