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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DOI：
10.1002/anie.201912119
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发表时间：
2019-11-28
影响因子：
16.6
通讯作者：
Lennox, Alastair J. J.
中科院分区：
文献类型：
--
作者：
Doobary, Sayad;Sedikides, Alexi T.;Lennox, Alastair J. J.
氟化烷基是生物活性化合物中的重要基序，对药代动力学、效力和构象产生积极影响。烯烃的氧化二氟化代表了其制备的重要策略，但目前的方法在其烯烃类型和对富电子、易氧化官能团的耐受性以及其安全性和可扩展性方面受到限制。在此，我们报告了一种对许多未活化的烯烃类型进行二氟化的方法，该方法能够耐受富电子官能团，从而得到其他方法无法获得的产品。成功的关键是使用“ex-cell”方法电化学生成高价碘介体，该方法避免了氧化底物分解。更可持续的条件可以带来高达十克规模的优异产量。
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.