美国俄亥俄州立大学Sevov, Christo S.团队报道了作为Csp²-Csp³偶联反应通用平台的持久性有机镍配合物。相关研究成果于2024年4月29日发表在《自然—化学》。

构建Csp²–Csp³键的重要性推动了电化学、光化学和热活化方法的发展，以还原偶联丰富的芳基和烷基亲电试剂。然而，这些方法仅限于非常特定的底物类别的偶联，并且需要专门的催化剂组和反应组。

该文中，研究人员展示了将这些无数策略整合到一组条件中，从而实现可靠的烷基-芳基偶联，包括那些以前未知的偶联。这些反应依赖于异常持久的作为C（sp²）–C（sp³）偶联的化学计量平台的有机镍配合物的发现。Ni的芳基、杂芳基或乙烯基络合物可以通过由相应的C（sp²）亲电试剂，进行温和的电还原而在多谱图规模上廉价地制备。

有机镍配合物可以直接分离、储存或伸缩，以可靠地使类药物分子多样化。最后，通过整合可溶性电池化学物质作为氧化还原引发剂，将该过程小型化至微摩尔规模，实现了对底物多样性的高通量探索。

附：英文原文

Title: Persistent organonickel complexes as general platforms for Csp2–Csp3 coupling reactions

Author: Dinh, Long P., Starbuck, Hunter F., Hamby, Taylor B., LaLama, Matthew J., He, Cyndi Q., Kalyani, Dipannita, Sevov, Christo S.

Issue&Volume: 2024-04-29

Abstract: The importance of constructing Csp2–Csp3 bonds has motivated the development of electrochemical, photochemical and thermal activation methods to reductively couple abundant aryl and alkyl electrophiles. However, these methodologies are limited to couplings of very specific substrate classes and require specialized sets of catalysts and reaction set-ups. Here we show a consolidation of these myriad strategies into a single set of conditions that enable reliable alkyl–aryl couplings, including those that were previously unknown. These reactions rely on the discovery of unusually persistent organonickel complexes that serve as stoichiometric platforms for C(sp2)–C(sp3) coupling. Aryl, heteroaryl or vinyl complexes of Ni can be inexpensively prepared on a multigram scale by mild electroreduction from the corresponding C(sp2) electrophile. Organonickel complexes can be isolated and stored or telescoped directly to reliably diversify drug-like molecules. Finally, the procedure was miniaturized to micromole scales by integrating soluble battery chemistries as redox initiators, enabling a high-throughput exploration of substrate diversity.

DOI: 10.1038/s41557-024-01528-7

Source: https://www.nature.com/articles/s41557-024-01528-7