Methylsulfenylation of Electrophilic Carbon Atoms: Reaction Development, Scope, and Mechanism

Abstract

An innovative method for the methylsulfenylation of electrophilic carbons was explored. Cheap and commercially available dimethyl sulfoxide (DMSO) was used as a source of the –SCH3 group. Chalcone, dibenzylideneacetone, and Morita–Baylis–Hillman adduct derivatives were successfully sulfenylated to give the corresponding products in moderate to high yields. Control experiments and DFT calculations revealed deoxygenation of DMSO and nucleophilic addition of a sulfur intermediate as key steps in the entire mechanism.

Diverse 3-Methylthio-4-Substituted Maleimides through a Novel Rearrangement Reaction: Synthesis and Selective Cell Imaging

“…We began to evaluate the reaction by employing the 4-chloro-substituted thiazolidine-2,4-dione ( 1b ) and the reaction conditions previously developed by our research group for the methylthiolation of Michael acceptors. , In the absence of potassium trichloroacetate (KCTA), no product was detected (Table , entry 1). The use of 1.0 equiv of the KTCA salt, however, afforded the desired maleimide derivative ( 2b ) in 46% isolated yield (Table , entry 2).…”

“…The ring opening results in the formation of isocyanate intermediate C. 29 A ring-closure step occurs through the attack of the carbanion on the isocyanate, affording a maleimide salt (D), which in turn is protonated by the CSA catalyst, affording E. This step is then followed by the interaction with the methylthiomethyl acetate (F), a key intermediate that is formed and was previously detected under similar reaction conditions. 23,24 The formation of these species requires DMSO, acetic acid, CSA, and a base (potassium trichloroacetate or sodium acetate). Finally, the attack of the sulfur atom from the maleimide on the methylthiomethyl acetate intermediate produces G, followed by the attack of sulfide on the thiocarbonyl group, affording spiro intermediate H. After deprotonation, this intermediate affords the desired product and formaldehyde and thioacetic acid as byproducts.…”

Application of DMSO as a methylthiolating reagent in organic synthesis

“…In the history of synthetic and pharmaceutical chemistry, β-thiocarbonyls are considered to be important compounds because of their intrinsic biological characteristics. In 2017, Amarante and Horta's group 63 realized the conversion of Michael acceptors including chalcone, dibenzylideneacetone, and Morita–Baylis–Hillman adduct derivatives 73 to the corresponding methylthiolated products 74 in moderate to high yields. The reaction was carried out with DMSO as the methylthiolating reagent and potassium trichloroacetate (KTCA) as the activator under microwave irradiation and followed by the addition of acetic acid at 100 °C.…”

Dimethyl Sulfoxide: Yesterday's Solvent, Today's Reagent

“…reported the methylthionylation of a broad range of compounds with activated double bonds such as chalcones 107 , Morita–Baylis–Hillman (MBH) adduct derivatives 108 and dibenzylideneacetones (DBA) 109 in DMSO 1 as a solvent as well as a reagent. The reactions were conducted in the presence of camphorsulfonic acid (CSA) as catalyst and 4 Å molecular sieves (MS) under microwave radiation at 100 °C (Scheme ) . As the authors described, the reaction of potassium trichloroacetate (KTCA) 106 with DMSO 1 provides the dimsyl anion 112 (a key intermediate) which cannot form in the presence of acetic acid.…”