Mechanistic Insights into the Nickel-Catalyzed Regioselective Carboxylation of Allylic Alcohols

The recently reported nickel-catalyzed direct carboxylation of allylic alcohol eliminates the necessity for pre-activation of substrates in traditional strategies and generates linear β, γ-unsaturated carboxylic acids with high E/Z selectivity. Motivated by the significant experimental advantages and the mechanistic ambiguity (in the C–O activation mode of the allylic alcohol, the rate- and regio-/stereoselectivity-determining steps, etc.), we conducted a detailed study on the mechanism of Ni-catalyzed carboxylation of allylic alcohols with density functional theory calculations. It is found that the reaction occurs via the activation of allylic alcohol, oxidative ligation, reduction, and carboxylation steps. The rate-determining step is the first step, in which the moisture of the reaction system plays a critical role. Through the hydrogen bonding network formed between water and the substrate, “proton-relay” occurs easily to generate the allylic hydrogen carbonate and to undergo the subsequent oxidative ligation steps. Meanwhile, the steric hindrance between CO2 and the allylic group during the coordination of CO2 is mainly responsible for the regioselectivity on the terminal carbon atom, and the E/Z selectivity is mainly determined by the thermodynamic stability of the E-substrates.