Department of Chemistry, Yale University, 225 Prospect St, New Haven, CT, USA.
Department of Pharmacology, Yale University, 333 Cedar St, New Haven, CT, USA.
Angew Chem Int Ed Engl. 2021 Jan 18;60(3):1116-1150. doi: 10.1002/anie.201913645. Epub 2020 Sep 24.
Fragment coupling reactions that form carbon-carbon bonds are valuable transformations in synthetic design. Advances in metal-catalyzed cross-coupling reactions in the early 2000s brought a high level of predictability and reliability to carbon-carbon bond constructions involving the union of unsaturated fragments. By comparison, recent years have witnessed an increase in fragment couplings proceeding via carbanionic and open-shell (free radical) intermediates. The latter has been driven by advances in methods to generate and utilize carbon-centered radicals under mild conditions. In this Review, we survey a selection of recent syntheses that have implemented carbanion- or radical-based fragment couplings to form carbon-carbon bonds. We aim to highlight the strategic value of these disconnections in their respective settings and to identify extensible lessons from each example that might be instructive to students.
片段偶联反应形成碳-碳键，在合成设计中是很有价值的转化。21 世纪初金属催化交叉偶联反应的进展，为涉及不饱和片段结合的碳-碳键构建带来了高度的可预测性和可靠性。相比之下，近年来，通过碳负离子和开壳（自由基）中间体进行的片段偶联反应有所增加。这是由于在温和条件下生成和利用碳中心自由基的方法的进步所推动的。在这篇综述中，我们调查了一些最近的合成，这些合成采用了碳负离子或自由基片段偶联来形成碳-碳键。我们的目的是突出这些在各自环境中的连接策略价值，并从每个例子中确定可扩展的经验，这些经验可能对学生有指导意义。
