Theoretical Investigation on the Mechanism of Ni ⁰ (enolate)–Ate Complex-Catalyzed C(sp ² )–F Bond Activation and the Origin of Alkali Metal Cations Modulating Enantioselectivity

This study employs density functional theory (DFT) calculations and ab initio molecular dynamics (AIMD) simulations to elucidate the mechanism of Ni0-catalyzed C(sp2)–F bond activation and unveils the pivotal role of alkali metal cations in modulating enantioselectivity. Results reveal that the reaction between indanone and NaOtBu in situ generates an enolate intermediate with the keto–enol tautomerism character, which enables inert C(sp2)–F bond activation, affording both enol- and keto-type products. Significantly, in the presence of Ni0(cod)2, the enolate coordinates to the Ni0 center to form a highly nucleophilic Ni0(enolate)–ate complex. Computational results show that the Ni0(enolate)–ate complex is an active species for the C(sp2)–F bond activation, which chemoselectively achieves a keto-type product. This unexpected Ni0-mediated SNAr pathway, which involves a Na+–nucleophile interaction, exhibits a lower activation energy than the other four pathways. The characteristic reactivity of the Ni0(enolate)–ate complex is attributed to the synergistic effect arising from the nucleophilic Ni0 center and Lewis acidic countercation of the Ni0(enolate)–ate complex. AIMD simulations further corroborate that an ensemble of multiple noncovalent interactions provides an indispensable driving force for the activation of the inert C(sp2)–F bond. Moreover, the alkali metal cation plays a decisive role in modulating both the reactivity and enantioselectivity. The experimentally observed R selectivity originates from a critical cation−π interaction that preferentially stabilizes the (R)-transition state, while the high reactivity is attributed to hydrogen bonding, which effectively stabilizes the transition state.