Umpolung Synthesis of Pyridyl Ethers by Bi V -Mediated O-Arylation of Pyridones
Umpolung Synthesis of Pyridyl Ethers by Bi V -Mediated O-Arylation of Pyridones
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Bi V 介导的吡啶酮 O-芳基化 Umpolung 合成吡啶醚
DOI：
10.1002/ange.202212873
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发表时间：
2022
影响因子：
--
通讯作者：
Ruffell K
中科院分区：
文献类型：
--
作者：
Ruffell K
我们报道了2-和4-吡啶酮与芳基硼酸的O-选择性芳基化反应受到一个模块化的双环体系的影响。通过对Ki6783和吡咯萘芬的简明合成，以及对库扎替布和高拉替尼的形式合成，证明了该方法是对传统的基于SNAR或交叉偶联的方法的补充，也是对吡啶醚的有效补充。计算研究表明，芳基化通过5元过渡态以协同方式进行。O-芳基化反应受动力学控制的区域选择性与之前BiV介导的吡啶酮芳基化反应相反，这主要归因于双环支架施加的几何约束。
We report that O‐selective arylation of 2‐ and 4‐pyridones with arylboronic acids is affected by a modular, bismacycle‐based system. The utility of this umpolung approach to pyridyl ethers, which is complementary to conventional methods based on SNAr or cross‐coupling, is demonstrated through the concise synthesis of Ki6783 and picolinafen, and the formal synthesis of cabozantib and golvatinib. Computational investigations reveal that arylation proceeds in a concerted fashion via a 5‐membered transition state. The kinetically‐controlled regioselectivity for O‐arylation—which is reversed relative to previous BiV‐mediated pyridone arylations—is attributed primarily to the geometric constraints imposed by the bismacyclic scaffold.