Electrochemical Synthesis of Isoxazolines: Method and Mechanism
Samuel David Lee Holman, Alfie G. Wills, Neal J. Fazakerley, Darren L. Poole, Diane M. Coe, Leonard A. Berlouis, Marc Reid
Abstract
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.