Electrochemical synthesis of isoxazolines: method and mechanism

Samuel D. L. Holman; Alfie G. Wills; Neal J. Fazakerley; Darren L. Poole; Diane M. Coe; Leonard Berlouis; Marc Reid

doi:10.1002/chem.202103728

Electrochemical synthesis of isoxazolines: method and mechanism

Samuel D. L. Holman, Alfie G. Wills, Neal J. Fazakerley, Darren L. Poole, Diane M. Coe, Leonard Berlouis, Marc Reid

Pure And Applied Chemistry

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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.

Original language	English
Article number	e202103728
Number of pages	13
Journal	Chemistry - A European Journal
Volume	28
Issue number	13
Early online date	25 Jan 2022
DOIs	https://doi.org/10.1002/chem.202103728
Publication status	Published - 1 Mar 2022

Keywords

isoxazoline
electrochemistry
cycloaddition
DFT
electrochemical method

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10.1002/chem.202103728Licence: CC BY 4.0

Holman-etal-Electrochemical-synthesis-of-isoxazolinesFinal published version, 6.75 MBLicence: CC BY 4.0

Accelerated Discovery and Development of New Medicines: Prosperity Partnership for a Healthier Nation
Kerr, W., Brown, C., Florence, A., Jamieson, C., Johnston, B., Murphy, J., Palmer, D. & Tomkinson, N.
EPSRC (Engineering and Physical Sciences Research Council)
1/01/19 → 30/09/24
Project: Research

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title = "Electrochemical synthesis of isoxazolines: method and mechanism",

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.",

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author = "Holman, {Samuel D. L.} and Wills, {Alfie G.} and Fazakerley, {Neal J.} and Poole, {Darren L.} and Coe, {Diane M.} and Leonard Berlouis and Marc Reid",

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TY - JOUR

T1 - Electrochemical synthesis of isoxazolines

T2 - method and mechanism

AU - Holman, Samuel D. L.

AU - Wills, Alfie G.

AU - Fazakerley, Neal J.

AU - Poole, Darren L.

AU - Coe, Diane M.

AU - Berlouis, Leonard

AU - Reid, Marc

PY - 2022/3/1

Y1 - 2022/3/1

N2 - 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.

AB - 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.

KW - isoxazoline

KW - electrochemistry

KW - cycloaddition

KW - DFT

KW - electrochemical method

U2 - 10.1002/chem.202103728

DO - 10.1002/chem.202103728

M3 - Article

SN - 0947-6539

VL - 28

JO - Chemistry - A European Journal

JF - Chemistry - A European Journal

IS - 13

M1 - e202103728

ER -

Electrochemical synthesis of isoxazolines: method and mechanism

Abstract

Keywords

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Accelerated Discovery and Development of New Medicines: Prosperity Partnership for a Healthier Nation

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