Deuterodehalogenation Under Net Reductive or Redox-Neutral Conditions Enabled by Paired Electrolysis.
Deuterodehalogenation Under Net Reductive or Redox-Neutral Conditions Enabled by Paired Electrolysis.
复制标题
通过配对电解实现净还原或氧化还原中性条件下的氘代脱卤。
DOI：
10.1002/anie.202218858
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Lin,Song
中科院分区：
文献类型：
--
作者：
Wood,Devin;Lin,Song
对氘化活性药物成分（API）的兴趣日益增加，因为氘化有望实现动力学同位素效应（KIE）调节API性能的微调。此外，氘同位素标记经常用于研究有机和生物有机反应机理，并促进复杂靶标的合成。因此，有机分子的高度选择性氘化的方法是非常需要的。在此，我们提出了一种利用廉价的氧化氘（D2O）作为氘源，通过自由基-极性交叉机制对苯基卤化物进行选择性氘脱卤的电化学方法。我们在一系列芳基和杂芳基苯基卤化物中证明了广泛的官能团相容性。此外，我们发现了一个连续的配对电解机制，它允许在含硫底物的净还原和整体氧化还原中性反应之间切换，只需改变所使用的牺牲还原剂的身份。
Interest in deuterated active pharmaceutical ingredients (APIs) is increasing as deuteration holds promise for kinetic isotope effect (KIE) regulated fine‐tuning of API performance. Moreover, deuterium isotope labeling is frequently carried out to study organic and bioorganic reaction mechanisms and to facilitate complex target synthesis. As such, methods for highly selective deuteration of organic molecules are highly desirable. Herein, we present an electrochemical method for the selective deuterodehalogenation of benzylic halides via a radical‐polar crossover mechanism, using inexpensive deuterium oxide (D2O) as the deuterium source. We demonstrate broad functional group compatibility across a range of aryl and heteroaryl benzylic halides. Furthermore, we uncover a sequential paired electrolysis regime, which permits switching between net reductive and overall redox‐neutral reactions of sulfur‐containing substrates simply by changing the identity of the sacrificial reductant employed.