Cobalt/Photoredox Catalyzed Desymmetrization of Oxo and Azabicycles via Asymmetric Reductive Coupling With Alkynes

ABSTRACT Bicyclo[2.2.1]heptane frameworks represent a privileged structural motif prevalent in numerous natural products and bioactive molecules. We report a one‐step, highly enantioselective and diastereoselective reductive protocol for the synthesis of oxa‐ and aza‐bicyclo[2.2.1]heptanes, enabled by [cobalt]/[photoredox] (Co/PC) catalysis. This methodology exploits heterobicyclic strained olefins as π ‐coupling partners to directly access enantiomerically enriched bicyclo[2.2.1]heptanes from a wide range of alkynes, including terminal alkynes, propargylic alcohols, and internal alkynes. Mechanistic investigations, supported by DFT calculations, reveal that the oxidative coupling between the alkyne and alkene constitutes both the enantio‐ and rate‐determining step. DIPEA serves as an efficient electron‐donor, while the in situ‐generated secondary ammonium salt acts as a competent proton source.