Electrochemical Synthesis of Isoxazolines: Method and Mechanism

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 via an electrochemically enabled regio- and diastereoselective reaction with electron-deficient alkenes. Additionally, in-situ reaction monitoring methods compatible with electrochemistry equipment have also been developed in order to probe the reaction pathway. Supporting analyses from kinetic (time-course) modeling and density functional theory support a stepwise, radical-mediated mechanism, and discounts hypothesized involvement of closed shell [3+2] cycloaddition pathways.