Direct Synthesis of α-Sulfenylated Ketones under Electrochemical Conditions

Abstract

We investigated the electrochemical sulfenylation reaction in both batch and continuous flow regimes, involving thiophenols/thiols and enol–acetates to yield α-sulfenylated ketones, without using additional oxidants or catalysts. Studies with different electrolytes were also performed, revealing that quaternary ammonium salts are the best mediators for this reaction. Notably, during the study of the reaction scope, a Boc-cysteine proved to be extremely tolerant to our protocol, thus increasing its relevance. The methodology also proved to be scalable in both batch and continuous flow conditions, opening up possibilities for further studies since these relevant functional groups are important moieties in organic synthesis.

Disulfides as versatile starting reagents: effective sulfonylation of alkenes with disulfides under electrochemical conditions

“…[33][34][35][36][37] Thiyl radicals are mostly generated, which are then added to multiple bonds. [38][39][40][41] In some cases, thiols dimerization is a side process, and the formed disulfides do not enter the sulfenylation reaction, which takes place in the case of thiols usage. [42][43][44] Sulfonylation often goes through the oxidative generation of sulfonyl radicals from sulfinic acids and their salts, [45][46][47][48] as well as sulfonyl hydrazides [49][50][51][52] (Scheme 1b).…”

Electrochemical Synthesis of α-Thiocyanated/Methoxylated Ketones Using Enol Acetates

“…In 2021, Terent’ev’s group reported on the electrochemical synthesis of fluorinated ketones from enol acetates with Langlois reagent (CF 3 SO 2 Na). In 2022, Oliveira’s group also developed the direct synthesis of α-sulfenylated ketones under electrochemical conditions. Afterward, Zhou and Wang’s group prepared the α-arylated ketones using enol acetates with aryl diazonium salts by an electrochemical way.…”

Electrochemical vicinal oxyazidation of α-arylvinyl acetates

“…The adoption of electrosynthesis in green and sustainable redox transformations has been experiencing a dynamic renaissance [15][16][17][18][19][20][21][22] not only because it employs the passage of charge instead of chemical oxidants or reductants but also offers opportunities for the precise control of reactivity by "dialing-in" the specific potential on demand [23][24][25]. Specifically, the electrochemical oxyfunctionalization of vinyl acetates has been developed to afford the corresponding α-fluorinated [26], -arylated [27], and -sulfenylated [28] ketones (Scheme 1B). In addition, electrochemical azidation [29][30][31][32][33] has also become a robust and reliable synthetic tool to incorporate azido functionality [34,35] into diverse organic frameworks.…”

“…Specifically, the electrochemical oxyfunctionalization of vinyl acetates has been developed to afford the corresponding α-fluorinated [ 26 ], -arylated [ 27 ], and -sulfenylated [ 28 ] ketones ( Scheme 1B ). In addition, electrochemical azidation [ 29 – 33 ] has also become a robust and reliable synthetic tool to incorporate azido functionality [ 34 – 35 ] into diverse organic frameworks.…”