Electrochemical Nickel-Catalyzed C(sp3)–C(sp3) Cross-Coupling of Alkyl Halides with Alkyl Tosylates

• Published in: Journal of the American Chemical Society 2023-08, Vol.145 (31), p.17023-17028
• Main Authors: Ibrahim, Malek Y. S., Cumming, Graham R., Gonzalez de Vega, Raquel, Garcia-Losada, Pablo, de Frutos, Oscar, Kappe, C. Oliver, Cantillo, David
• Format: Article
• Language: English
• Subjects: Communication
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.3c07313

Formation of new C­(sp3)–C­(sp3) bonds is a powerful synthetic tool to increase molecular diversity, which is highly sought after in medicinal chemistry. Traditional generation of carbon nucleophiles and more modern cross-electrophile-coupling methods typically lack sufficient selectivity when cross-coupling of analogous C­(sp3)-containing reactants is attempted. Herein, we present a nickel-catalyzed, electrochemically driven method for the coupling of alkyl bromides with alkyl tosylates. Selective cross-coupling transformations were achieved even between C­(sp3)-secondary bromides and tosylates. Key to achieve high selectivity was the combination of the tosylates with sodium bromide as the supporting electrolyte, gradually generating small amounts of the more reactive bromide by substitution and ensuring that one of the reaction partners in the nickel-catalyzed electroreductive process is maintained in excess during a large part of the process. The method has been demonstrated for a wide range of substrates (>30 compounds) in moderate to good yields. Further expanding the scope of electroorganic synthesis to C­(sp3)–C­(sp3) cross-coupling reactions is anticipated to facilitate the switch to green organic synthesis and encourage future innovative electrochemical transformations.