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

Azetidines are prominent structural scaffolds in bioactive molecules, medicinal chemistry, and ligand design for transition metals. However, state-of-the-art methods cannot be applied to intramolecular hydroamination of allylic amine derivatives despite their underlying potential as one of the most...

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Published inJournal of the American Chemical Society Vol. 145; no. 28; pp. 15360 - 15369
Main Authors Park, Steve H., Bae, Geunsu, Choi, Ahhyeon, Shin, Suyeon, Shin, Kwangmin, Choi, Chang Hyuck, Kim, Hyunwoo
Format Journal Article
LanguageEnglish
Published WASHINGTON American Chemical Society 19.07.2023
Amer Chemical Soc
Subjects
catalysts
catalytic activity
Chemistry
Chemistry, Multidisciplinary
cobalt
electricity
electrochemistry
kinetics
Lewis bases
ligands
oxidation
Physical Sciences
regioselectivity
Science & Technology
FUNCTIONALIZATION
ALKENES
CATALYSIS
HYDROFUNCTIONALIZATION
AMINATION
HETEROCYCLES
ENANTIOSELECTIVE HYDROAMINATION
STEREOSELECTIVE-SYNTHESIS
UNACTIVATED OLEFINS
C(SP)-H
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Summary:Azetidines are prominent structural scaffolds in bioactive molecules, medicinal chemistry, and ligand design for transition metals. However, state-of-the-art methods cannot be applied to intramolecular hydroamination of allylic amine derivatives despite their underlying potential as one of the most prevalent synthetic precursors to azetidines. Herein, we report an electrocatalytic method for intramolecular hydroamination of allylic sulfonamides to access azetidines for the first time. The merger of cobalt catalysis and electricity enables the regioselective generation of key carbocationic intermediates, which could directly undergo intramolecular C–N bond formation. The mechanistic investigations including electrochemical kinetic analysis suggest that either the catalyst regeneration by nucleophilic cyclization or the second electrochemical oxidation to access the carbocationic intermediate is involved in the rate-determining step (RDS) of our electrochemical protocol and highlight the ability of electrochemistry in providing ideal means to mediate catalyst oxidation.
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ISSN:0002-7863
1520-5126
1520-5126
DOI:10.1021/jacs.3c03172