Organic Chemistry

Direct Hydroxylarylation of Benzylic Carbons (sp3/sp2/sp) via Radical-Radical Cross-Coupling Powered by Paired Electrolysis

Authors

Abstract

Diaryl alcohol moieties are widespread in pharmaceuticals. Existing methods for the synthesis of diaryl alcohols require the use of pre-functionalized benzylic alcohols, aromatic aldehydes or ketones as starting materials. Herein, the first convergent paired electrochemical approach to the direct hydroxylarylation of unactivated benzylic carbons (sp3/sp2/sp) is declared. This protocol features direct functionalization of unactivated benzylic C(sp3)–H bonds and benzylic sp2/sp-carbons, mild conditions (open air, room temperature), environmentally friendly procedure (without any external catalyst/mediator/additive), and direct access to sterically hindered alcohols from inexpensive and readily available alkyl/alkenyl/alkynylbenzenes. Mechanistic studies, including divided-cell experiments, isotope labeling, radical trapping, electron paramagnetic resonance (EPR), reaction kinetics, and cyclic voltammetry, strongly support the proposed radical-radical cross-coupling between transient ketyl radicals and persistent radical anions. Gram-scale synthesis and diversification of drug derivative have visualized the tremendous potential of this protocol for practical applications.

Version notes

In the new version, we introduced the previous work of other research groups in detail, highlighting that our method is more economical and green.

Content

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Supplementary material

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Supporting information
Supporting information