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

Intramolecular
asymmetric carbopalladation of N-aryl acrylamides
followed by intermolecular trapping of the resulting
σ-C­(sp3)–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.