Unlocking Epoxide Radical Anion Reactivity for Asymmetric Cross-Coupling by Copper Metallaphotoredox

The ability to tame radical anions that feature both an unpaired spin and a charge is critical for synthetic chemistry, enabling the construction of diverse chemical bonds via unique reaction pathways and promoting advances in the area of synthesis. In this regard, C(sp³)-rich epoxide radical anions are particularly attractive but often elusive, highly reactive intermediates. Classic methods to access epoxide radical anions exploit single-electron chemistry by using dissolving alkali, sacrificial electrodes, or redox metals. However, these methods are often prohibitive because of reagent safety issues and over-reduction, limiting their wide implementation, especially in asymmetric synthesis. Herein, we realize a copper metallaphotoredox platform to unlock epoxide radical anion reactivity, allowing the controlled generation of epoxide radical anions and their enantioconvergent cross-coupling with diverse, readily available partners via distonic radical anion intermediates. These discoveries permit highly regio-, chemo-, and enantioselective hydrocyanation and hydroalkynylation, thereby providing a general solution to the challenge of epoxide radical anion-mediated enantioselective chemical diversification.