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DMSO/Tertiary Amine Activation of Elemental Sulfur: A New Route to Thioaurones

Recent work by the Nguyen group has revealed that DMSO, in combination with a tertiary amine (e.g., Et3N or NMP), works to activate elemental sulfur such that it participates in a reaction to form two C–S bonds, producing thioaurones 2 (Table 1).1 Thioaurone-type compounds are interesting dye/photoswitch materials, usually made via processes that involve sulfides and thiols.2 Therefore, these […]

DMSO as a Methine Synthon: K2S2O8-Mediated Synthesis of Quinolines

The quinoline structure is frequently found in pharmaceutically valuable compounds. Therefore, there are multiple routes to synthesize this heterocycle. Most of these routes, however, suffer from the involvement of delicate or exotic precursors and expensive transition metal catalysts. Recently, the Singh group reported a new route to substituted quinolones 3 that starts with readily available aryl ketone 1, […]

Direct C–H Trifluoromethylation at the Benzylic Position in DMSO

The development of methods to efficiently incorporate trifluoromethyl groups into compounds continues to be of interest to pharmaceutical, agrichemical, and material chemists. A recent report by the Hamashima group demonstrates the rapid, direct trifluoromethylation at the benzylic position of 2-methylbenzophenones and 2-methylacetophenones 1 using only the Togni reagent II (2) and photoirradiation (365 nm) in DMSO (Table […]

DMSO–Superbase Route to Dioxabicyclooctanes from Simple Ketones and Acetylenes

The number of self-assembly reactions involving acetylenes under KOt-Bu– and KOH–DMSO superbase conditions continues to grow.1 The Trofimov group has shown that simple ketones and acetylene can self-assemble in a one-pot KOH–DMSO reaction to provide 6,8-dioxabicyclo[3.2.1]octanes (DOBCOs) (1), which, upon treatment with acid, isomerize to the corresponding acetyl-substituted dihydropyrans 2 (Scheme 1).2 There is interest in species like compound 1 as […]

Copper-Catalyzed Synthesis of Multisubstituted Indoles in DMSO

The indole subunit is widely seen in many pharmaceutically and biologically active compounds. Its importance, therefore, has spurred the development of numerous methods to synthesize this subunit. Additionally, new methods continue to be developed to overcome some of the deficiencies or limitations of past methods such as harsh conditions, exotic starting materials, and expensive or […]

DMSO as a Reagent in the In Situ Generation of Isocyanates: A One Pot Method to Synthesize Unsymmetrical Ureas and Carbamates

Isocyanates are highly valued synthetic intermediates. Unfortunately, they are usually synthesized using toxic phosgene. Recently, the Rousseaux group published work demonstrating the in situ generation of various aryl isocyanates through reaction of DMSO, trifluoroacetic anhydride (TFAA), DBU, CO2, and an aryl amine.1 This method not only avoids using phosgene, it also eliminates the need to isolate […]

Light-Promoted Synthesis of 3,4-Dihydroisocoumarin Derivatives in DMSO

Isocoumarins exhibit a wide range of biological activity. Therefore, they are often synthetic targets. Many of the recently developed methods to form the isocoumarin or 3,4-dihydroisocoumarin structure rely on metal catalysts and relatively high temperatures. In 2018, Xia and Yang’s group reported a light-promoted method in DMSO to form substituted 3,4-dihydroisocoumarins.1 This method does not require […]

CO2/DMSO-Catalyzed Oxidation of Benzylic and Allylic Alcohols

DMSO oxidations of alcohols are well known (e.g., Swern, Pfitzner-Moffatt, and Parikh-Doering) and widely used. These methods, however, require activation of the alcohol with large excesses of promoters that are often both toxic and relatively difficult to handle. Therefore, DMSO oxidation techniques are often not amenable to large scale reactions. Das and co-workers have recently […]

DMSO as the Oxidant in the α-Sulfenylation of Unsaturated Ketones

The number of reactions continues to grow where the interaction of DMSO and iodine result in the functionalization of a C–H bond. (See Synthesis Corner posts from July 28 & March 29, 2017 and October 29, 2016 for recent examples.) An example published in 2018 by the Prabhu group introduces the completely regioselective αʹ-sulfenylation of an α,β-unsaturated […]

DMSO as a C1 Building Block in the Co(III)-Catalyzed Synthesis of Quinolines

Quinolines are common structural units in pharmaceuticals and other biologically-active compounds. Therefore, there are numerous named reactions to construct this motif (e.g., Skraup, Pfitzinger, etc.). As many of these reactions require harsh conditions and/or unusual starting materials, efforts have been made to develop milder methods using readily available starting materials with broader substrate scope. Recently […]