Synthesis Corner

DMSO as the carbon source in transition-metal-free α-Csp3-H methylenation

  The ability to make the C=C bond at a targeted position has always been of high interest to synthetic chemists.  Recently, Guo et al. reported a method by which to activate a hydrogen at the alpha position of a ketone in order to make a new C=C bond at that position (Figure 1).1  Their […]

DMSO as the carbon source for sp3 C-H olefination

The examples of dimethyl sulfoxide acting as a one carbon source for methylenation reactions continue to grow. (See recent Synthesis Corner posts from January, 2018—“DMSO as the carbon source in transition-metal-free α-Csp3-H methenylation” and March, 2018—“DMSO as a one carbon source in the transition-metal-free synthesis of quinolones.”) Recently, Namitharan et al. reported on the synthesis […]

Visible Light Promoted Synthesis of Indoles in DMSO

The indole ring is widely found in pharmaceutical compounds, agrochemicals, and natural products. Therefore, methods to produce this heterocycle are important. Traditional methods to synthesize the indole ring often suffer from the requirement of exotic starting materials, from poor functional group tolerance, and from the generation of significant amounts of undesirable byproducts. Therefore, greener, more […]

DMSO as the Solvent for Cu(I)-Catalyzed Reactions: The Synthesis of Pyrrole Derivatives

Recently, Zhao’s group reported on the oxidative cyclization of maleimides with amines and alkyne esters to form pyrrole and dihydropyrrole derivatives (Figure 1).1 The importance of these five-membered nitrogen-containing heterocyclic compounds cannot be overstated, as they are common in biologically- and pharmaceutically-active compounds. Therefore, the chemical literature is filled with examples of routes to form these […]

Synthesis of β-Amino Alcohol Derivatives through a Photo-Induced Reaction in DMSO

  Synthetic routes to β-amino alcohols and their derivatives are extremely important as these compounds are widespread in natural products, pharmaceuticals, and agrochemicals. In 2018, Yu’s group published an interesting photoredox-induced radical relay method in DMSO to synthesize functionalized β-amino alcohol derivatives.1 Unlike other established methods to simultaneously construct a C-N and a C-O bond across the carbon-carbon […]

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-I2-Promoted Insertion of Isocyanide into the N–H Bond of Amines: Synthesis of Ureas

Metal-catalyzed insertion reactions of isocyanides into amines have been developed with the ultimate goal of synthesizing nitrogen-containing heterocycles. These routes have had problems in that isocyanides often strongly coordinate to metal catalysts, and they often undergo polymerization under these conditions.1 Because of this, there is interest in developing metal-free methods. The metal-free insertion of an […]

DMSO/I2: Simple and Green Syntheses of Imidazoles

Imidazoles are crucial building blocks for many pharmaceuticals and agrichemicals.  Trisubstituted imidazoles are particularly important. Therefore, several methods have been developed to synthesize these structural units; however, these methods generally have several drawbacks, including the need for complex and harsh reaction conditions and toxic transition metal reagents. Additionally, they sometimes produce many side products. Therefore, […]

Visible-Light-Mediated Synthesis of γ-Ketoesters in DMSO

γ-Ketoesters are common synthetic building blocks. Therefore, diverse synthetic methods have been developed to prepare these compounds. Recently, the Liu group reported a visible-light-mediated method, using compact fluorescent light (CFL), where the oxidative coupling of readily available vinylarenes and bromocarboxylates, followed by a Kornblum-type oxidation in DMSO, furnishes the desired γ-ketoester (equation in Table 1, […]