Decoding C-O vs C-C Bond Selectivity in Nickel-Metallaphotoredox Carboxylic Acid Cross-Coupling

Understanding how catalytic systems dictate product selectivity is crucial for advancing sustainable cross-coupling chemistry. While nickel-photoredox dual catalysis has unlocked CC and CO bond formation from carboxylic acids and aryl halides, the mechanistic origins of this divergence have remained elusive. Here, we combine systematic experimentation with density functional theory (DFT) calculations and electrochemical analysis to uncover the key parameters that govern whether CC or CO bonds are formed. We show that the halide identity of the aryl electrophile exerts a decisive influence: iodides strongly favor esterification via a low-barrier reductive elimination pathway, bromides promote decarboxylative CC coupling, and chlorides, with prohibitively high CO barriers, yield exclusively CC products. Complementary experiments reveal that both photocatalyst loading and halide additives modulate selectivity, in direct agreement with computed energy landscapes. Together, these insights establish a unified mechanistic framework that explains divergent reactivity across seemingly similar conditions. By demonstrating how subtle changes in halide, photocatalyst, and additives toggle reaction outcomes, our study provides predictive design principles for exploiting carboxylic acids in nickel-photoredox catalysis.