A nickel-catalysed radical mechanism by three-component dimensionality reduction strategies: a theoretical study

Three-component coupling reactions represent a potent approach for synthesizing complex products. Radical-initiated three-component coupling reactions hold significant promise in synthetic chemistry but are often challenged by the high reactivity of radical species and the complex coordination environment of transition metal catalysts. Herein, we employed density functional theory (DFT) and ab initio molecular dynamics (AIMD) simulations to investigate the mechanism of three-component olefin difunctionalization. Our study reveals that the dimensionality reduction in multi-component coupling reactions is fundamentally governed by a metal-free radical-radical cycle mechanism. A concentration-driven coordination mode shift modulates the reactivity of the Ni(0) centre, thereby enabling the multi-component reaction to proceed with high selectivity. Pauli repulsion plays a decisive role in determining enantiomeric isomerism in the radical capture step during two-component cross-coupling. This work provides a theoretical comprehension for the rational design of efficient radical-mediated multi-component coupling reactions.