En Route to Enantioenriched Quaternary Stereocenters via Lewis Base/Palladium Cooperative Catalysis

The prevalence of quaternary stereogenic centers in bioactive molecules coupled with innate challenges associated with their enantioselective preparation continues to provide powerful impetus for the development of catalytic asymmetric methods capable of their construction. Herein, we describe a cooperative isothiourea Lewis base-palladium catalyst system that enables the enantioselective alkylation of α-substituted-α-cyano esters with allyl methanesulfonate. While the levels of enantioselection are modest, this study represents the first time we have successfully constructed quaternary-substituted stereogenic centers using this Lewis base-palladium cooperative catalysis scheme. Further, this strategy constitutes a departure from ligand-based enantiocontrol and suggests that, when using acidic pro-nucleophiles, the development of protocols where Lewis base catalysis can outcompete direct deprotonation might be within reach.