转自：康龙化成

Water-Stable 2-Pyridylboron Reagents: Pd-Catalyzed 2-Pyridylation Reaction of Aryl Halides

Wei Li, Yu Chen, Ruyi Yuan, Xuhao Jia, 

Yingming Yao, and Li Zhang*

Key Laboratory of Organic Synthesis of Jiangsu Province College of Chemistry, Chemical Engineering and Materials Science,Soochow University

—Angew. Chem. Int. Ed., 2025, 10.1002/anie.202500315.

Recommended by Shi Li_MOC

KEYWORDS: Base-free Suzuki coupling,Pd catalysis, 2-pyridylation(反应类型), protonated 2-pyridylation reagent, aryl halides (原料),2-pyridinyl arene (产物),C(sp2)–C(sp2) (成键类型)

ABSTRACT: The stability of 2-pyridylation reagents is a long-standing issue in cross-coupling chemistry due to hydrolysis. However, as the use of pyridine-based pharmaceuticals continues to increase, there is a high demand for stable and reactive 2-pyridylation reagents. Herein, a general strategy to prepare water-stable 2-pyridylboron reagents has been developed. The application of the water-stable 2- pyridylboron reagents in a neutral Suzuki-Miyaura coupling with a halide scavenger enables an efficient 2-pyridylation reaction of aryl halides.

Background

Robustness test of 2-pyridylation reagents

Preparation of 2-pyridylboron reagent 

Synthetic scope (selected)

Proposed mechanism

L. Zhang and co-workers report a solution of “2-pyridyl problem” in Suzuki coupling that involves preparing a protodeboronation-resistant 2-pyridylboron reagent1 and then reacting this under modified, base-free conditions. Two protodeboronation pathways (stepwise hydrolysis / protodeboronation and direct protodeboronation) are envisioned for this water-stable 2-pyridylboron reagent, both of which are kinetically or thermodynamically unfavorable under neutral, aqueous conditions. The subsequent cross-coupling of reagent 1can be achieved under base-free conditions via the intermediacy of a cationic Pd(II) complex, which is generated through the use ofa halide scavenger, ZnO. A potential drawback of this strategy is the requirement for reagent 1 to be prepared from traditional unstable 2-pyridyl organoboron reagents.

（转自：康龙化成）