Precise borylation of targeted methyl group via an orderly chain-walking strategy.

Bao, Yinwei; Hu, Chenke; Zheng, Lixuan; Wu, Yitao; Huang, Feihe; Lu, Zhan · Sci Adv · 2026

basic_science · Level V

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Abstract

C─H functionalization is an attractive approach in organic synthesis due to its directness and efficiency. Nevertheless, achieving precise differentiation among multiple methyl groups with highly similar chemical environments remains a notable challenge. Here, an orderly chain-walking borylation strategy was introduced via targeted hook and enduring slide that enables precise remote C(<i>sp<sup>3</sup></i>)-H borylation and affords a series of "Y-shape" boron analogs through rational desymmetric ligand design. This method exhibits broad substrate scope, good functional group tolerance, and high atom economy and achieves a chain-walking distance of 32 carbons, and we hope it will promote cross-disciplinary innovation in areas including materials science and pharmaceuticals.