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

Abstract

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.