Ni‐Catalyzed Selective Crosscoupling for Diarylmethane‐Containing Boronic Ester Synthesis

Boron‐functionalized diarylmethanes represent valuable scaffolds in medicinal chemistry, yet their efficient synthesis remains challenging due to the instability and reactivity of boronic ester motifs. Herein, we report a modular nickel‐catalyzed crosselectrophile coupling strategy for the selective construction of diarylmethane‐containing boronic esters from readily available arylboronic esters and benzyl halides. The reaction proceeds under mild, base‐free conditions, delivering a wide range of structurally diverse products in up to 94% yield with excellent chemoselectivity. Mechanistic investigations, supported by density functional theory (DFT) calculations and stoichiometric experiments, reveal a competitive pathway scenario in which a single‐electron transfer (SET)‐mediated radical pathway is kinetically favored and governs the observed selectivity. The protocol exhibits broad substrate scope and high functional group tolerance and is amenable to gram‐scale synthesis without chromatographic purification. Furthermore, the synthetic utility is demonstrated through streamlined access to pharmaceutically relevant molecules, including ketoprofen and antihistamine derivatives. Notably, the resulting boronic ester products display bioactivity‐modulating potential, showing synergistic cytotoxicity with bupivacaine in cancer cell models. This work provides a practical and mechanistically informed platform for the synthesis of functionalized diarylmethanes and expands the utility of boron‐containing building blocks in drug discovery and development.