Chemodivergent Organolanthanide-Catalyzed C–H α-Mono-Borylation of Pyridines

Chemodivergent synthetic methodologies enable the efficient introduction of structural diversity into high-value organic products via simple chemical alterations. In this regard, C–H activation and functionalization of pyridinoid azines are important transformations in the synthesis of many natural products, pharmaceuticals, and functional materials. Reflecting on azinyl nitrogen lone-pair steric repulsion, its tendency to irreversibly coordinate metal ion catalysts, and the electron deficiency of pyridine, C–H functionalization at the important α-position remains challenging. Thus, developing earth-abundant catalysts for α-selective azine mono-functionalization is an attractive target for chemical synthesis. Here, the selective organolanthanide-catalyzed α-mono-borylation of a diverse series of 18 pyridines is reported using Cp*2LuCH(TMS)2 (Cp* = η5-C5Me5) (TMS = SiMe3) and affording valuable precursors for subsequent functionalization. Experimental and theoretical mechanistic data reported here support the intermediacy of a C–H-activated η2-lanthanide-azine complex, followed by intermolecular α-mono-borylation via σ-bond metathesis. Notably, varying the lanthanide identity and substrate substituent electronic character promotes marked chemodivergence of the catalytic selectivity: smaller/more electrophilic lanthanide3+ ions and electron-rich substrates favor selective α-C–H functionalization, whereas larger/less electrophilic lanthanide3+ ions and electron-poor substrates favor selective B–N bond-forming 1,2-dearomatization. Such lanthanide series catalytic chemodivergence is, to our knowledge, unprecedented.