Synthesis Corner

Sulfur Ylide Reactions

Epoxides are ethers, also called oxiranes, in which the oxygen atom is contained in a three membered ring. This highly strained molecule is very reactive. The most commonly encountered reactions of epoxides are those in which the ring is opened by a nucleophile. Such reactions are advantageously performed in DMSO because DMSO is inert to […]

Dichlorocyclopropene Activation of DMSO for Swern Type Oxidations

  Oxidations of primary alcohols using activated DMSO to produce aldehydes are important reactions. Oxalyl chloride is a common activator for DMSO (Swern oxidation) and has been widely used. However, oxalyl chloride has some drawbacks in that it is volatile and toxic. Additionally, the oxalyl chloride/DMSO pair must be kept cold (less than –60 °C) […]

DMSO as the oxidant for Cu-catalyzed synthesis of multisubstituted furans

  Copper-catalyzed synthetic strategies have gained popularity because the economic, sustainability, and toxicological characteristics of copper are attractive compared to several other metal catalysts.  Many of these reactions depend on the oxidation of Cu(I) to Cu(II).  This has often been achieved with peroxides or with molecular oxygen. In an effort to broaden the scope of […]

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 a one carbon source in the transition-metal-free synthesis of quinolones

DMSO is known to be a valuable source of a variety of one carbon synthons.1 New work by Tiwari et al. uses DMSO as the one carbon source in an atom-economical and environmentally benign approach to the synthesis of 3-substituted quinolones.2  This work involves transformations that are very similar to the work done by the Guo […]

Sulfuric acid-promoted DMSO oxidation of benzylic alcohols

DMSO is a useful reagent for selective oxidation of primary alcohols to aldehydes.  These oxidations generally involve DMSO activation by another species such as dicyclohexylcarbodiimide [Pfitzner-Moffatt oxidation], oxalyl chloride [Swern oxidation] or pyridine sulfur trioxide [Parikh-Doering].  While these reactions have been widely used, they have some disadvantages in terms of atom economy, cost, difficult reaction […]

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 […]

CuI/DMSO-mediated synthesis of 3-sulfonyl dihydrofurans

Five-membered rings containing oxygen are common and recurring motifs in biologically-active compounds. Therefore, the development of routes to synthesize these ring systems is of great interest. Recently, Chang et al. developed a one-pot (3 + 2) annulation method to synthesize 3-sulfonyl dihydrofurans (Equation 1).1 This method uses readily-available and relatively inexpensive CuI and DMSO to give […]

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 […]

Photocatalysis in DMSO: Reductive Fluoroalkylation of Nitrones

Organofluorine compounds are of growing importance in medicinal chemistry, so new methods to produce them continue to generate interest. In 2018, Dilman et al. reported a method to add fluorinated groups to nitrones (1) to produce fluorinated hydroxylamines (3, possible precursors to pharmacophoric amines) (Figure 1).1 The mild conditions (a photocatalyst, ascorbic acid, and DMSO) of […]