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Cobalt-electrocatalytic C–H hydroxyalkylation of<i>N</i>-heteroarenes with trifluoromethyl ketones

Tianyu He, Chaoqiang Liang, Shenlin Huang

2022Chemical Science33 citationsDOIOpen Access PDF

Abstract

-heteroarenes and trifluoromethyl ketones. The reaction starts with reversing the polarity of ketones to nucleophilic ketyl radicals through an electrocatalytic proton-coupled electron transfer (PCET), followed by radical addition to heteroarenes and rearomatization to afford tertiary alcohol products. Importantly, the merging of paired electrolysis and cobalt catalysis is crucial to this regioselective C-H hydroxyalkylation of heteroarenes, and thus avoids several known competing pathways including the spin-center shift (SCS) process. Collectively, this protocol provides straightforward access to heteroaryl trifluoromethyl carbinols, featuring ideal atom economy, excellent regioselectivity, and paired redox-neutral electrolysis.

Topics & Concepts

TrifluoromethylCobaltElectrolysisChemistryCatalysisElectrochemistryRedoxMedicinal chemistryCombinatorial chemistryOrganic chemistryElectrodePhysical chemistryElectrolyteAlkylFluorine in Organic ChemistryCatalytic C–H Functionalization MethodsRadical Photochemical Reactions
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