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Electrochemical Synthesis of Isoxazolines: Method and Mechanism
Author(s) -
Holman Samuel D. L.,
Wills Alfie G.,
Fazakerley Neal J.,
Poole Darren L.,
Coe Diane M.,
Berlouis Leonard A.,
Reid Marc
Publication year - 2022
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202103728
Subject(s) - cycloaddition , electrochemistry , reaction mechanism , mechanism (biology) , aryl , alkyl , chemistry , combinatorial chemistry , density functional theory , computational chemistry , electrode , organic chemistry , catalysis , physics , quantum mechanics
An electrochemical method for the green and practical synthesis of a broad range of substituted isoxazoline cores is presented. Both aryl and more challenging alkyl aldoximes are converted to the desired isoxazoline in an electrochemically enabled regio‐ and diastereoselective reaction with electron‐deficient alkenes. Additionally, in‐situ reaction monitoring methods compatible with electrochemistry equipment have been developed in order to probe the reaction pathway. Supporting analyses from kinetic (time‐course) modelling and density functional theory support a stepwise, radical‐mediated mechanism, and discounts hypothesised involvement of closed shell [3+2] cycloaddition pathways.