Integrating Achiral Brønsted Base and Chiral Bisguanidinium for Enantioselective Phospha-Michael Addition to Chalcones

The capability of classical chiral cationic phase-transfer catalyst (ccPTC) in facilitating interphase transfer of inorganic bases for asymmetric synthesis has been well recognized. However, the combination of ccPTC with achiral Brønsted bases featuring wide-ranging basicity for asymmetric organic transformation is less explored, as the racemic background reaction promoted by such organo-soluble base is generally difficult to suppress. Here, we report a highly enantioselective phospha-Michael addition reaction mediated by the neutral base 4-dimethylaminopyridine (DMAP) and ccPTC bisguanidinium (BG), wherein the chiral cationic BG snatches the ionic nucleophile phosphinothioite from the protonated DMAP via a cation exchange process. The newly formed chiral ion pair resulted in the enhancement of the reactivity of the phosphinothioite and allowed it to undergo the subsequent enantiocontrolled addition pathway. The reaction furnishes α-chiral phosphine sulfides with high synthetic utility in high yields and enantioselectivities. Detailed mechanistic studies indicated the crucial impact of confined structural features and positive charge delocalization of chiral bisguanidinium on the reaction reactivity and stereoselective outcomes.