Chiral oxalamide phosphine (COAP)-Pd-catalyzed enantioselective cascade formal [4 + 1] annulation for enantioenriched 2,3-disubstituted indolines and further DFT study on regio- and stereocontrol

Abstract

A chiral oxalamide phosphine (COAP)-Pd-catalyzed asymmetric cascade formal [4 + 1] annulation was developed between racemic vinyl benzoxazinones and N-tosylhydrazone sodium salts. The corresponding trans-2,3-disubstituted indoline products with contiguous stereogenic centers were obtained in good yields with high diastereo- and enantioselectivity. The catalytic outcomes and computational DFT study showed that the biphilic transformation proceeded by a dynamic kinetic asymmetric transformation (DYKAT) process. The enantio-determining step is a stereoselective migratory insertion of Pd(II)-carbene into a pendant chiral π-allylpalladium-COAP complex, followed by reductive elimination to fulfill the annulation.