Enantioselective (3+2)-Annulation of ß-Keto Esters with Azoalkenes towards Bicylic Dihydropyrroles via Cooperative Palladium and Brønsted Acid Catalysis

A cooperative catalytic process through Palladium and Brønsted acid activation has been developed for the conjugate addition of cyclic ß-keto esters to azoalkenes directly followed by hemiaminal formation upon cyclization. This transformation was enabled by utilizing chiral Pd-aqua complexes as combined Brønsted acid-base catalysts. Thus, bicyclic and highly functionalized dihydropyrroles with two contiguous quaternary stereogenic centers were formed in excellent yields as single diastereomers and with exceptional enantioselectivity.