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Electronic Activation Enables the Borylation of Alkyl C–H Bonds in Saturated Nitrogen Heterocycles

Kyan A. D’Angelo, R.L. Zheng, Isaac Furay Yu, Melody J. Tang, Chris La, Richard T. Wetterer, John F. Hartwig

2025Journal of the American Chemical Society7 citationsDOI

Abstract

Catalytic functionalization of C-H bonds is a valuable strategy for the synthesis and diversification of organic compounds. The catalytic borylation of heteroaromatic C-H bonds is well established, but the analogous borylation of alkyl C-H bonds in saturated heterocycles remains underdeveloped. Reactions with improved catalysts recently reported for the borylation of alkyl C-H bonds occurred with a narrow range of such nitrogen heterocycles. Here, we describe a broadly applicable approach to activate C-H bonds in saturated nitrogen heterocycles for iridium-catalyzed borylation by installing a group on nitrogen that increases the reactivity of specific C-H bonds. Mechanistic studies reveal that the electron withdrawing groups accelerate the rate of borylation by enhancing the energetics of multiple steps within the catalytic cycle.

Topics & Concepts

BorylationChemistryAlkylCatalysisReactivity (psychology)NitrogenOrganic chemistryPhotochemistryCombinatorial chemistryBond cleavageOrganocatalysisOrganic synthesisPolymer chemistryCatalytic cycleFunctional groupMedicinal chemistryLeaving groupCatalytic C–H Functionalization MethodsOrganoboron and organosilicon chemistryCatalytic Cross-Coupling Reactions
Electronic Activation Enables the Borylation of Alkyl C–H Bonds in Saturated Nitrogen Heterocycles | Litcius