Theoretical mechanistic study of 4CzIPN/Ni0-metallaphotoredox catalyzed enantioselective desymmetrization of cyclicmeso-anhydrides

Visible-light-induced inexpensive photocatalyst and transition metal dual catalytic cross-coupling has attracted much attention for efficiently constructing various chemical bonds. The 4CzIPN/Ni0-metallaphotoredox catalyzed enantioselective desymmetrization of cyclic meso-anhydrides with benzyl trifluoroborates has been systematically investigated using density functional theory (DFT) calculations. A radical mechanism merging reductive quenching (PC-*PC-PC--PC) and nickel catalytic cycles (Ni0-NiII-NiIII-NiI-Ni0) is favourable. It consists of seven major processes: single-electron reduction of *PC by benzyl trifluoroborates to generate benzyl radical, ligand exchange, oxidative addition, radical addition, reductive elimination, reduction of NiI by PC- complex via single-electron transfer (SET) process to obtain ground-state PC, and the ion exchange to afford the desired product enantio-enriched keto-acids and regenerate Ni0 catalyst. The oxidative addition is not only the enantio-determining step but also the rate-determining step of the catalytic cycle. In addition, we tried to disclose the origin of high enantioselectivity from both the steric and electronic effects and explain the origin of diastereoselectivity based on the proposed mechanism. Meanwhile, the difference of catalytic activity between Ni0 and NiII as the initial catalysts is caused by the different activation energy barriers based on their respective favourable reaction pathways. This study will hopefully benefit the future understanding of such photoredox-mediated dual catalyzed asymmetric synthesis.