Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
Angew Chem Int Ed Engl. 2021 Jul 12;60(29):15767-15790. doi: 10.1002/anie.202011901. Epub 2021 Feb 4.
The design of synthetic routes by retrosynthetic logic is decisively influenced by the transformations available. Transition-metal-catalyzed C-H activation has emerged as a powerful strategy for C-C bond formation, with myriad methods developed for diverse substrates and coupling partners. However, its uptake in total synthesis has been tepid, partially due to their apparent synthetic intractability, as well as a lack of comprehensive guidelines for implementation. This Review addresses these issues and offers a guide to identify retrosynthetic opportunities to generate C-C bonds by C-H activation processes. By comparing total syntheses accomplished using traditional approaches and recent C-H activation methods, this Review demonstrates how C-H activation enabled C-C bond construction has led to more efficient retrosynthetic strategies, as well as the execution of previously unattainable tactical maneuvers. Finally, shortcomings of existing processes are highlighted; this Review illustrates how some highlighted total syntheses can be further economized by adopting next-generation ligand-enabled approaches.
通过反合成逻辑设计合成路线，受可用转化的影响很大。过渡金属催化的 C-H 活化已成为形成 C-C 键的有力策略，已经开发了无数种方法来用于各种底物和偶联伙伴。然而，它在全合成中的应用一直很缓慢，部分原因是其明显的合成复杂性，以及缺乏全面的实施指南。这篇综述解决了这些问题，并提供了一种通过 C-H 活化过程生成 C-C 键的反合成机会的指南。通过比较使用传统方法和最近的 C-H 活化方法完成的全合成，本综述展示了 C-H 活化如何实现 C-C 键构建，从而导致更有效的反合成策略，以及以前无法实现的战术动作的执行。最后，突出了现有工艺的缺点；本综述说明了通过采用下一代配体辅助方法可以进一步节省一些突出的全合成成本。
