Electrochemical Halogenation and Etherification of Alcohols Enabled by a Halide-Coupled Phosphine Oxidation.

ABSTRACT: Phosphine-mediated nucleophilic substitution reactions of alcohol substrates, such as the Appel and Mitsunobu reactions, have found widespread applications in chemical synthesis. However, their reliance on stoichiometric chemical oxidants (e.g., carbon tetrachloride and azodicarboxylate reagents) often results in limited functional group tolerance, environmentally hazardous wastes, and unsatisfactory reaction economy. Herein, we describe a user-friendly electrochemical Appel reaction employing readily available tetrabutylammonium halide salts ( ⁿ Bu₄N⁺X^-, X = Cl, Br, and I) as the halogen source. A survey of alcohol substrates revealed broad functional group tolerance, including complex pharmaceutical and bioactive scaffolds. Electroanalyt

SUBMITTER: Hale EA 

PROVIDER: S-EPMC12679309 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature