Palladium-Catalyzed Enantioselective Domino Heck/Intermolecular C-H Bond Functionalization: Development and Application to the Synthesis of (+)-Esermethole

Intrarmolecular asymmetric carbopalladation of N-aryl acrylamides followed by intermolecular trapping of the resulting sigma-C(sp(3))-Pd complex by azoles afforded 3,3-disubstituted oxindoles in good yields with excellent enantioselectivities. Two C-C bonds were created with concurrent formation of an all-carbon quaternary stereocenter. Oxadiazole substituted oxindoles were subsequently converted to pyrroloindolines by an unprecedented reductive cyclization protocol. The utility of this chemistry was illustrated by an enantioselective synthesis of (+)-esermethole.