（来源：康龙化成）

转自：康龙化成

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

Kyan A. D’Angelo, Ruyou Zheng, Isaac F. Yu, Melody J. Tang, Chris La, Richard T. Wetterer, and John F. Hartwig*

Department of Chemistry, University of California, Berkeley, California 94720, United States

—J. Am. Chem. Soc. 2025, 10.1021/jacs.5c15431

Recommended by Depei Meng_MC4

KEY WORDS:C–H activation, borylation, Ircatalysis (反应类型), C(sp3)–B (成键类型), Saturated nitrogen heterocycles,Saturated Cyclic Sulfonamides(原料), alkyl Bpin (产物)

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.

(B) Prior borylations of saturated azacycles. (C) This report on site-selective borylation of electronically activated saturated aza-heterocycles

Time courses for the borylation of 5-membered heterocycles

Scope of the borylation of saturated cyclic sulfonamides

Downstream transformations of boronic ester 6b

In summary, Prof. Hartwig groupdescribes a broadly applicable approach to activate C–H bonds in saturated nitrogen heterocyclesfor iridium-catalyzed borylation by installing a group on nitrogen that increases the reactivity of specific C–H bonds. This studydemonstrates that manipulation of electronic properties of the substrate can extend the borylation of alkyl C−H bonds to medicinally relevant structures, including many that have not undergone selective functionalization at C−H bonds previously. 

总地来说，Hartwig教授课题组报道了一种普适性策略：通过在氮原子上引入特定基团增强特定C─H键反应活性，从而实现饱和氮杂环化合物中C─H键的铱催化硼化。该研究表明，通过调控底物电子特性，可将烷基C─H键硼化反应拓展至药物相关结构体系，并用于多种此前从未实现过C─H键选择性官能化的分子。