Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, 510640, P. R. China.
Angew Chem Int Ed Engl. 2021 May 17;60(21):12038-12045. doi: 10.1002/anie.202017271. Epub 2021 Apr 12.
The solvent-switched hydroxylation and oxygenation of α-difluoro(thio)methylated carbanions with molecular oxygen under mild conditions are reported. This strategy tames the redox reactions of the in situ generated hydroperoxy difluoromethylsulfides, in which solvent-bonding can alter their reactivity and switch the oxidation selectivities. These controllable three-component reactions of gem-difluoroalkenes, thiols and molecular oxygen afford various useful α-difluoro(thio)methylated alcohols and ketones in high yields. Significantly, this protocol has been applied in the synthesis different bioactive molecules. Mechanism studies enable the detection of the hydroperoxy difluoromethylsulfide intermediates and exclude the thiol-based radical pathway.
本文报道了在温和条件下，利用分子氧对α-二氟（硫）甲基化碳负离子进行溶剂调控的羟化和氧化反应。该策略控制了原位生成的过氧二氟甲基亚砜的氧化还原反应，其中溶剂键合可以改变其反应性并切换氧化选择性。该方法可实现偕二氟烯烃、硫醇和分子氧的可控三组分反应，以高产率得到各种有用的α-二氟（硫）甲基化醇和酮。值得注意的是，该方案已应用于不同生物活性分子的合成。通过机理研究，可以检测到过氧二氟甲基亚砜中间体，并排除了基于硫醇的自由基途径。
