Copper-Catalyzed Three-Component Photo-ATRA-Type Reaction for Asymmetric Intermolecular C-O Coupling

Atom transfer radical addition (ATRA) reaction of alkenes has had a significant impact on the field of radical difunctionalization of alkenes. Particularly, in the three-component photo-ATRA-type processes, a rich chemical space and structural diversity could be achieved by smart combination of redox-active radical precursors and the third coupling components (e.g., halides, C-, N-, and O-nucleophiles) under mild conditions. However, the inherent complicated mechanisms involving radical chain or outer-sphere SET of the incipient radical intermediates have led to a dearth of general catalytic methods for highly enantioselective variants, especially those regarding asymmetric inter-molecular C-O bond formation. Here, we report a visible-light-induced copper-catalyzed asymmetric three-component photo-ATRA-type reaction of alkenes with oxime esters and carboxylic acids. In this process, a highly enantioselective intermolecular C-O cross-coupling between incipient sp(3)-hybridized carbon radicals and carboxylic acids was enabled by the formation of an aryl pi-bond-engaged [sigma + pi]-copper complex. This working hypothesis renders naphthyl or extended conjugation of alkenes to be suitable substrates and allows good stereocontrol. This three-component photo-ATRA-type reaction exhibits broad substrate scope and high functional group tolerance with respect to each component, giving the desired cross-coupling products with generally good yields and enantioselectivity (>70 examples; up to 97% ee). Preliminary experimental and computational studies are also performed to gain insight into the mechanism and stereoregulatory elements. This finding provides a promising platform for the development of other enantioselective benzylic-type radical-based cross-coupling reactions.

Automated summary

Atom transfer radical addition (ATRA) reaction of alkenes has a significant impact in the field of radical difunctionalization of alkenes. A novel copper-catalyzed asymmetric three-component photo-ATRA-type reaction is reported, which enables highly enantioselective intermolecular C-O cross-coupling between carbon radicals and carboxylic acids.