Issue 1, 2023

Cobalt-electrocatalytic C–H hydroxyalkylation of N-heteroarenes with trifluoromethyl ketones

Abstract

Trifluoromethyl carbinols and N-heteroarenes are both prevalent in bioactive molecules. However, access to high-value pharmacophores combining these two functional groups still remains a challenge. Herein, we report an electro-chemical redox-neutral coupling for the synthesis of N-heteroaryl trifluoromethyl carbinols from readily available N-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.

Graphical abstract: Cobalt-electrocatalytic C–H hydroxyalkylation of N-heteroarenes with trifluoromethyl ketones

Supplementary files

Article information

Article type
Edge Article
Submitted
19 set 2022
Accepted
21 nov 2022
First published
21 nov 2022
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2023,14, 143-148

Cobalt-electrocatalytic C–H hydroxyalkylation of N-heteroarenes with trifluoromethyl ketones

T. He, C. Liang and S. Huang, Chem. Sci., 2023, 14, 143 DOI: 10.1039/D2SC05198B

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