Electrochemical Vicinal Difluorination of Alkenes: Scalable and Amenable to Electron-Rich Substrates
Electrochemical Vicinal Difluorination of Alkenes: Scalable and Amenable to Electron-Rich Substrates
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烯烃的电化学邻位二氟化：可扩展且适用于富电子基质
DOI：
10.1002/ange.201912119
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发表时间：
2019
影响因子：
--
通讯作者：
Doobary S
中科院分区：
文献类型：
--
作者：
Doobary S
含氟烷基是生物活性化合物中的重要基元，对药物动力学、药效和构象有积极的影响。烯烃的氧化二氟化反应是一种重要的制备方法，但目前的方法在烯烃类型、对富电子、易氧化官能团的耐受性以及安全性和可扩展性方面都存在局限性。在这里，我们报告了一种方法，用于对许多未活化的烯烃类型的二氟化反应，该方法可以容忍富电子官能团，从而得到否则无法获得的产品。成功的关键是使用“ex-cell”方法电化学生成高价碘介体，避免了底物的氧化分解。可持续的条件越好，产量就越高，最高可达10个基数。
Fluorinated alkyl groups are important motifs in bioactive compounds, positively influencing pharmacokinetics, potency and conformation. The oxidative difluorination of alkenes represents an important strategy for their preparation, yet current methods are limited in their alkene‐types and tolerance of electron‐rich, readily oxidized functionalities, as well as in their safety and scalability. Herein, we report a method for the difluorination of a number of unactivated alkene‐types that is tolerant of electron‐rich functionality, giving products that are otherwise unattainable. Key to success is the electrochemical generation of a hypervalent iodine mediator using an “ex‐cell” approach, which avoids oxidative substrate decomposition. The more sustainable conditions give good to excellent yields in up to decagram scales.