美国哈佛大学Richard Y. Liu团队报道了迁移芳基交叉偶联。相关研究成果发表在2024年12月18日出版的《美国化学会杂志》。

交叉偶联反应的一个基本性质是区域特异性，这意味着键形成的位置由亲电基团上的离去基团的位置决定。通常，实现不同的取代模式需要合成一种新的、相应的起始材料异构体。作为替代方案，研究人员建议开发交叉偶联变体，以便从相同的偶联伙伴那里获得多种结构异构体。

该文中，研究人员首先证明，大体积的钯催化剂可以通过暂时形成金属炔物种，来促进芳基卤化物的有效、可逆的转位。尽管这一过程几乎处于热中性平衡状态，但将其与逐渐加入合适的亲核试剂相结合，可实现异构中间体的动态动力学拆分，和非常规产物异构体的高产率。

该方法适用于一系列以氧和氮为中心的亲核试剂，并适用于许多常见的官能团。科廷-哈米特动力学方案得到了计算和实验数据的支持，为扩展这种迁移交叉耦合概念提供了一个通用的力学框架。

附：英文原文

Title: Migratory Aryl Cross-Coupling

Author: Yoshiya Sekiguchi, Polpum Onnuch, Yuli Li, Richard Y. Liu

Issue&Volume: December 18, 2024

Abstract: A fundamental property of cross-coupling reactions is regiospecificity, meaning that the site of bond formation is determined by the leaving group’s location on the electrophile. Typically, achieving a different substitution pattern requires the synthesis of a new, corresponding starting-material isomer. As an alternative, we proposed the development of cross-coupling variants that would afford access to multiple structural isomers from the same coupling partners. Here, we first demonstrate that a bulky palladium catalyst can facilitate the efficient, reversible transposition of aryl halides by temporarily forming metal aryne species. Despite the nearly thermoneutral equilibrium governing this process, combining it with the gradual addition of a suitable nucleophile results in dynamic kinetic resolution of the isomeric intermediates and high yields of unconventional product isomers. The method accommodates a range of oxygen- and nitrogen-centered nucleophiles and tolerates numerous common functional groups. A Curtin–Hammett kinetic scheme is supported by computational and experimental data, providing a general mechanistic framework for extending this migratory cross-coupling concept.

DOI: 10.1021/jacs.4c15086

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c15086