Electrocatalytic Access to Azetidines via Intramolecular Allylic Hydroamination: Scrutinizing Key Oxidation Steps through Electrochemical Kinetic Analysis

Abstract

Azetidines are prominent structural scaffolds in bioactivemolecules,medicinal chemistry, and ligand design for transition metals. However,state-of-the-art methods cannot be applied to intramolecular hydroaminationof allylic amine derivatives despite their underlying potential asone of the most prevalent synthetic precursors to azetidines. Herein,we report an electrocatalytic method for intramolecular hydroaminationof allylic sulfonamides to access azetidines for the first time. Themerger of cobalt catalysis and electricity enables the regioselectivegeneration of key carbocationic intermediates, which could directlyundergo intramolecular C-N bond formation. The mechanisticinvestigations including electrochemical kinetic analysis suggestthat either the catalyst regeneration by nucleophilic cyclizationor the second electrochemical oxidation to access the carbocationicintermediate is involved in the rate-determining step (RDS) of ourelectrochemical protocol and highlight the ability of electrochemistryin providing ideal means to mediate catalyst oxidation.