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 intermolecular 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 sp3-hybridized carbon radicals and carboxylic acids was enabled
by the formation of an aryl π-bond-engaged [σ + π]-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.