Nickel-Catalyzed Asymmetric Reductive Carbo-Carboxylation of Alkenes with CO2

Reductive carboxylation of organo (pseudo)halides with CO 2 is a powerful method to provide carboxylic acids quickly. Notably, the catalytic reductive carbo-carboxylation of unsaturated hydrocarbons via CO 2 fixation is a highly challenging but desirable approach for structurally diverse carboxylic acids. However, there are only a few reports but no examples of alkenes via transition-metal catalysis. Herein, we report the first asymmetric reductive carbo-carboxylation of alkenes with CO 2 via nickel catalysis. A variety of aryl (pseudo)halides, such as aryl bromides, aryl triflates and inert aryl chlorides of particular note, undergo the reaction smoothly to give important oxindole-3-acetic acid derivatives bearing a C3-quaternary stereocenter. This transformation features mild reaction conditions, wide substrate scope, facile scalability, good to excellent chemo-, regio- and enantio-selectivities. Importantly, the method is highlighted by the formal synthesis of (-)-Esermethole, (-)-Physostigmine and (-)-Physovenine, as well as the total synthesis of (-)-Debromoflustramide B, (-)-Debromoflustramine B and (+)-Coixspirolactam A, opening an avenue for the total synthesis of chiral natural products with CO 2 .