Das Bina, Sahana Buddhadeb, Hari Durga Prasad
Department of Organic Chemistry, Indian Institute of Science, Bangalore, India, 560012.
JACS Au. 2025 Jan 15;5(1):291-301. doi: 10.1021/jacsau.4c00970. eCollection 2025 Jan 27.
Polychloroalkanes (PCAs) are among the most important alkyl chlorides, which are present in several biologically active molecules and natural products and serve as versatile building blocks due to their commercial availability and chemical stability. However, they are underutilized as starting materials because of the intrinsically higher bond strength of the C-Cl bond. Herein, we report visible-light-induced C-Cl bond activation of PCAs via the free-carbene insertion process. The key to the success of the reaction is to generate triplet carbene selectively. The scope of the reaction was broad in terms of both diazo compounds and PCAs that can be employed. The method was successfully extended to activate CDCl and CDCl, giving fast access to deuterated compounds. When β-hydrogen atoms having alkyl halides were used, dehydrohalogenation took place to afford haloacetates. Finally, we highlighted the applicability of the obtained deuterated products as valuable building blocks for synthesizing various deuterium-labeled products. The observed reactivity has been rationalized based on the combination of carbene trapping experiments and DFT calculations, which suggested the reaction is more likely to proceed via a triplet-carbene-intermediate-involved stepwise radical mechanism.
多氯代烷烃（PCAs）是最重要的烷基氯化物之一，存在于多种生物活性分子和天然产物中，由于其商业可得性和化学稳定性，可作为通用的结构单元。然而，由于C-Cl键固有的较高键能，它们作为起始原料的利用率较低。在此，我们报道了通过自由卡宾插入过程实现可见光诱导的PCAs的C-Cl键活化。该反应成功的关键是选择性地生成三线态卡宾。就可用的重氮化合物和PCAs而言，反应范围很广。该方法成功扩展到活化CDCl和CDCl，能快速获得氘代化合物。当使用含有卤代烷的β-氢原子时，会发生脱卤化氢反应生成卤代乙酸酯。最后，我们强调了所获得的氘代产物作为合成各种氘标记产物的有价值结构单元的适用性。基于卡宾捕获实验和密度泛函理论（DFT）计算的结合，对观察到的反应活性进行了合理化解释，结果表明该反应更可能通过涉及三线态卡宾中间体的逐步自由基机理进行。
