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Synthesis 2025; 57(13): 2124-2130
DOI: 10.1055/s-0043-1775467
paper
Bürgenstock Special Section 2023 – Future Stars in Organic Chemistry

Electro-Oxidative Platform for Nucleophilic α-Functionalization of Ketones

Rakesh Mondal‡
a   Department of Molecular Chemistry and Materials Science, The Weizmann Institute of Science, 7610001 Rehovot, Israel
,
Nicolas Jacob‡
b   Minakem Recherche, 145 Chemin des Lilas, 59310 Beuvry-la-Forêt, France
,
Maxime Devuyst 
b   Minakem Recherche, 145 Chemin des Lilas, 59310 Beuvry-la-Forêt, France
,
Mathilde Quertenmont
b   Minakem Recherche, 145 Chemin des Lilas, 59310 Beuvry-la-Forêt, France
,
Gleb Averochkin
a   Department of Molecular Chemistry and Materials Science, The Weizmann Institute of Science, 7610001 Rehovot, Israel
,
Stav Deri
a   Department of Molecular Chemistry and Materials Science, The Weizmann Institute of Science, 7610001 Rehovot, Israel
,
Lior Galmidi
a   Department of Molecular Chemistry and Materials Science, The Weizmann Institute of Science, 7610001 Rehovot, Israel
,
Daniel Gordon-Levitan
a   Department of Molecular Chemistry and Materials Science, The Weizmann Institute of Science, 7610001 Rehovot, Israel
,
Moran Feller
a   Department of Molecular Chemistry and Materials Science, The Weizmann Institute of Science, 7610001 Rehovot, Israel
,
Julien C. Vantourout∗
c   Syngenta Crop Protection AG, Schaffauserstrasse, 4332 Stein, Switzerland
,
Pierre-Georges Echeverria  ∗
b   Minakem Recherche, 145 Chemin des Lilas, 59310 Beuvry-la-Forêt, France
,
Samer Gnaim∗
a   Department of Molecular Chemistry and Materials Science, The Weizmann Institute of Science, 7610001 Rehovot, Israel
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Abstract

The significance of α-functionalization of carbonyl compounds arises from its frequent use in synthetic organic chemistry. Consequently, there is a substantial and constant demand for the creation of strategies that facilitate the efficient execution of such valuable transformation. In this context, herein is presented a universal electrochemical oxidative platform for the α-derivatization of ketones with nucleophiles, employing an umpolung reactivity. This approach has been successfully employed in three distinct transformations involving C–C and C–X bond formation via straightforward nucleophilic substitution or cycloaddition reaction pathways. Furthermore, the implementation of this methodology in flow using a commercially available reactor demonstrated its inherent scalability.

Key words

electrosynthesis - alpha-functionalization of carbonyls - umpolung - electrochemistry - flow chemistry

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0043-1775467.
  • Supporting Information


Publication History

Received: 13 December 2024

Accepted after revision: 05 March 2025

Article published online:
09 April 2025

© 2025. Thieme. All rights reserved

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

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