康 · 学术 | Reaction of the Day No. 1479

转自：康龙化成

Nickel-Catalyzed Suzuki–Miyaura Cross-Coupling Reaction of Aliphatic Alcohol Derivatives

Chloe D. Wong, Lauren C. Bradford, Nadia Hirbawi, and Elizabeth R. Jarvo*

Department of Chemistry, University of California, Irvine, California 92617, USA

—Angew.Chem. Int. Ed. 2025, 10.1002/anie.202509657

Recommended by Rui Jin_MC5 and Shi Li_MOC

KEY WORDS: Suzuki–Miyauracoupling (XC), Ni catalysis, enantioselective (反应类型), C(sp2)-C(sp3) (成键类型), aliphatic sulfonates, alcohols, aryl boronic acids (原料), aryl alkane, enantioenriched α-aryl and heteroaryl glutarimides (产物), NaI, one-pot, NiBr2(dme), Dtbbpy, chiral bisoxazoline, CBN ligand, PROTAC (其他)

ABSTRACT:Reactions leveraging readily available starting materials are valuable for synthetic utility, especially for late-stage functionalization. Herein, we report a nickel-catalyzed Suzuki–Miyaura cross-coupling (XC) reaction of aliphatic sulfonates with aryl boronic acids. This reaction provides straightforward access to an array of arylated products in good yield. We have established a one-pot protocol allowing for the arylation of alcohols in a single reaction vessel. Additionally, an asymmetric reaction was developed to provide enantioenriched α-aryl and heteroaryl glutarimides in good yield and enantioselectivity.

Background and this work: Suzuki–Miyaura reaction progress toward development of C(sp3) coupling

Substrate scope for aliphatic mesylate and boronic acid

Enantioselective reaction scope of α‐aryl glutarimides

One‐pot arylation of alcohols

Proposed mechanism

In conclusion, Elizabeth R. Jarvo et al. report anickel-catalyzed Suzuki–Miyaura XC reaction of aliphatic sulfonates with aryl boronic acids for the installation of aryl groups. The reaction features a broad scope of aliphatic mesylates and boronic acids, including heteroaryl boronic acids. The reaction can be performed in a one-potmanner, allowing for the direct arylation of alcohols. Mechanistic studies confirmed the stereoablative nature of the reaction and the intermediacy of alkyl radicals. Finally, we rendered the transformation to be enantioselective with a chiral bisoxazoline ligandfor the synthesis of enantioenriched bioactive building blocks.

加利福尼亚大学欧文分校Elizabeth R. Jarvo课题组报道了一种镍催化脂肪族磺酸酯与芳基硼酸的Suzuki-Miyaura交叉偶联反应，可以良好的收率直接获得多种芳基化产物。同时，该策略具有广泛的底物范围，多种脂肪族甲磺酸酯及硼酸类化合物（包括杂芳基硼酸）均与体系兼容。其次，通过一锅法反应实现了醇类底物的原位芳基化反应。机理研究证实了该反应的立体消蚀性以及烷基自由基的中介性。此外，通过使用手性双噁唑啉配体，还可实现相应的对映选择性转化，为合成高度对映体富集的生物活性砌块提供了新策略。

（转自：康龙化成）

转自：市场资讯