Synthesis of α-sulfenyl monoketones via a metal-free oxidative cross dehydrogenative coupling (CDC) reaction

Abstract

α-Sulfenyl ketones are potential precursors which find a variety of applications in organic synthesis. Their typical synthesis requires pre-functionalized starting materials and two to three step synthetic sequences. In addition, the selective pre-functionalization of unsymmetrical ketones is a challenge, which limits the synthesis of the desired sulfenylated ketones. To overcome these disadvantages, a metal-free, convenient one-step strategy for synthesizing α-sulfenyl ketones at ambient temperature via a cross-dehydrogenative coupling (CDC) strategy has been developed with a broad substrate scope. Therefore, this CDC strategy for C-S bond formation is attractive and may find wide applications in organic synthesis.

Recent Advances in Iodine‐Promoted C−S/N−S Bonds Formation

“…Although there are some reports for thiolation of ketones with aryl thiols through cross dehydrogenative coupling (CDC) strategy,t he similar reaction with heterocyclic thiols is still challenging and attractive. [103] In 2016, Prabhu and co-workers developed an iodine-promoted regioselective sulfenylation of the a-CH 3 on ketones 121 or 123 in the presence of competitive a-CH 2 or a-CH group, and varieties of heterocyclic thiols and thiones were well-tolerated in this reaction (Scheme 41 a). [104] However,t he reaction of thiophenol with ketone failed to afford the expectedp roduct.…”

Assessing Methodologies to Synthesize α‐Sulfenylated Carbonyl Compounds by Green Chemistry Metrics

“…The reaction also tolerated a wide scope of monoketones (products 28 – 30 ), although when pure aliphatic ketones bearing a long alkyl chain were used, there was a competition for sulfenylation to both alkyl chains (product 30 ). It should be noted that high chemical yields were obtained in the reaction of diketones with both, benzoxazole‐2‐ and benzothiazole‐2‐thiones, but only benzoxazole‐2‐thiones showed reactivity when reacted with monoketones [20e] . This reaction has a low atom economy of 15 % and 22 % for di‐ and mono‐ketones, respectively, owing to the use of the oxidant and a Brønsted acid.…”

“…Later, other methodologies based on the oxidative coupling of thiols and underivatized carbonyl compounds have appeared in the literature [20a,b,e,f,h–o,t] . For example, 1,3‐diketones have been further studied in the following reports.…”

“…The first developed methodology consisted in the cross‐dehydrogenative coupling (CDC) of β‐diketones using K 2 S 2 O 8 as oxidant in the presence of HClO 4 (Scheme 8). [20b] The same methodology could also be applied to monoketones [20e] . In both cases a variety of aromatic thiones were used as thiol equivalents to yield the α‐sulfenylated products with good to high yields (up to 96 % yield).…”

Substituted α‐Sulfur Methyl Carbanions: Effective Homologating Agents for the Chemoselective Preparation of β‐Oxo Thioethers from Weinreb Amides

“…Metal‐catalyzed S–H insertion into diazocarbonyls are not preferred options as a consequence of the somewhat limited selectivity and efficiency ( path d ) . Novel synthetic tools include the catalyst‐free insertion of Corey–Chaykovsky type ylides into aryl thiols introduced by Burtoloso ( path e ) and Samec's Pd/Au catalyzed click‐type chemistry ( path f ), inter alia …”