Construction of Chiral C2-Quaternary Indolines via Palladium-Catalyzed Decarboxylative Asymmetric Amination

The catalytic asymmetric synthesis of functionalized C2-quaternary indoline scaffolds has garnered significant attention in organic synthesis and drug discovery due to the inherent challenges and potential applications. Herein, we present a facile approach utilizing a Pd-catalyzed intramolecular decarboxylative asymmetric amination of vinyl benzoxazepinones, leading to the efficient construction of challenging chiral 2-vinyl-2-aryl/alkyl indoline frameworks in good yields with high enantioselectivities (>50 examples, up to 83% yield and 97% ee). Furthermore, these chiral indolines can be readily scaled up and further modified to access complex polycyclic indoline structures. We also synthesized several indoline-based ligands that exhibit promising efficiency as chiral catalysts in asymmetric reactions. Computational studies provided insight into the inner-sphere asymmetric amination mechanism.