Upgrading Sodium-Mediated Deprotonative Borylation to Catalytic Regimes: Regioselective Control and Mechanistic Implications

Organoboron compounds are essential to pharmaceutical synthesis, yet current catalytic C-H borylation methods remain largely limited to transition-metal and borenium catalysts. Deprotonative borylation presents a complementary approach for functionalizing acidic C-H bonds, but has traditionally required stoichiometric amounts of organometallic bases. Herein, we report the prototypal example of catalytic deprotonative borylation mediated by sodium. The use of an iminoborane as a trapping agent is key to the catalytic system, where unstable metalated intermediates are rapidly trapped to form a sodium borylamide, which can deprotonate the substrate to achieve catalytic turnover. Optimization of reaction conditions allows the borylation of base-sensitive substrates, such as fluoroarenes and pyridines, under noncryogenic conditions, affording good to excellent yields. Furthermore, selective stepwise borylation of multiple acidic C-H bonds can be achieved through stoichiometric control of the iminoborane reagent. A comprehensive mechanistic understanding of this transformative reaction has been established through density functional theory calculations, kinetic studies, and the isolation of key catalytic intermediates characterized by X-ray diffraction and NMR spectroscopy.