Visible-Light Photoredox-Catalyzed Remote Difunctionalizing Carboxylation of Unactivated Alkenes with CO2.

Catalytic difunctionalization of alkenes is a powerful and efficient tool to synthesize complex molecules from simple starting materials. Remote difunctionalization of unactivated alkenes is more challenging but highly attractive tactic to install two functional groups across long distances. Herein, we report the first remote difunctionalization of alkenes with CO 2 . This visible-light photoredox catalysis strategy provides a facile method to synthesize a series of carboxylic acids, such as non-natural α-amino acids, bearing valuable fluorine- or phosphorus-containing functional groups. Moreover, this versatile protocol shows mild reaction conditions, broad substrate scope, and good functional group tolerance. Based on DFT calculations, the observed reaction starts via radical addition to an unactivated alkene to smoothly form a new carbon radical. The following 1,5-hydrogen atom transfer process, which is considered to be the rate-limiting step, generates a more stable benzylic radical. In contrast to previous reports of direct coupling or single-electron oxidation of such radical species, experimental and computational studies suggest the reduction of the benzylic radicals by an Ir(II) species generates the corresponding benzylic carbanions as the key intermediates, which further undergo nucleophilic attack with CO 2 to generate carboxylates. Following this mechanistic study, diverse electrophiles, including aldehydes, ketones and benzylic bromides, are also applicable in such transformation, demonstrating a general strategy for redox-neutral remote difunctionalization of unactivated alkenes.