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Kinetic and thermodynamic control of C(sp <sup>2</sup> )–H activation enables site-selective borylation

Jose B. Roque, Alex M. Shimozono, Tyler P. Pabst, Gabriele Hierlmeier, Paul O. Peterson, Paul J. Chirik

2023Science42 citationsDOIOpen Access PDF

Abstract

Catalysts that distinguish between electronically distinct carbon-hydrogen (C–H) bonds without relying on steric effects or directing groups are challenging to design. In this work, cobalt precatalysts supported by N -alkyl-imidazole–substituted pyridine dicarbene (ACNC) pincer ligands are described that enable undirected, remote borylation of fluoroaromatics and expansion of scope to include electron-rich arenes, pyridines, and tri- and difluoromethoxylated arenes, thereby addressing one of the major limitations of first-row transition metal C–H functionalization catalysts. Mechanistic studies established a kinetic preference for C–H bond activation at the meta -position despite cobalt-aryl complexes resulting from ortho C–H activation being thermodynamically preferred. Switchable site selectivity in C–H borylation as a function of the boron reagent was thereby preliminarily demonstrated using a single precatalyst.

Topics & Concepts

BorylationChemistrySteric effectsArylCobaltCatalysisPincer movementReagentPyridineAlkylCombinatorial chemistrySelectivityMedicinal chemistryStereochemistryOrganic chemistryCatalytic C–H Functionalization MethodsOrganoboron and organosilicon chemistryCatalytic Cross-Coupling Reactions
Kinetic and thermodynamic control of C(sp <sup>2</sup> )–H activation enables site-selective borylation | Litcius