Sulfonic Acid‐Catalyzed Autoxidative Carbon‐Carbon Coupling Reaction under Elevated Partial Pressure of Oxygen

Abstract

An aerobic organocatalytic oxidative CC bond formation reaction of benzylic CH bonds with various C-nucleophiles is described. The coupling reaction proceeds by simply stirring the substrates under elevated partial pressure of oxygen in the presence of a sulfonic acid catalyst at room temperature. Elevation of the pressure enables the reaction of a broad scope of nucleophile substrates otherwise showing poor reactivity at ambient pressure. The benzylic CH bonds of xanthene, acridanes, isochromane and related heterocycles could be functionalized with nucleophiles including ketones, 1,3-dicarbonyl compounds and aldehydes. Electron-rich arenes could be utilized as nucleophiles at elevated temperatures. The reactions are believed to proceed via autoxidation of the benzylic CH bonds to the hydroperoxides and subsequent nucleophilic substitution catalyzed by sulfonic acids

Interplay of Method Development and Mechanistic Studies – From Aerobic Oxidative Coupling to Radical Reactions via Alkenyl Peroxides

“…Under these conditions, the coupling product 2 was isolated in 90% yield and various other ketones could also be coupled with xanthene (Scheme 4). 8,11 Scheme 3 An initial working model of the autoxidative coupling reaction, including the formation of the observed by-product 3…”

“…Again, by applying elevated pressure and temperature, we were able to broaden the product scope somewhat (Scheme 5). 8,11 Malonates, aldehydes and electron-rich benzenes could be used as nucleophiles. In the case of aldehydes, the isolated products turned out to be the over-oxidized carboxylic acids.…”

“…The latter, as well as a few other compounds with benzylic C-H bonds, reacted much better at elevated partial pressures of oxygen (Scheme 6). 8,11 As can be seen, the substrates are restricted to heterocycles. Diarylmethanes, however substituted, showed no reactivity under these conditions.…”

CAN‐mediated Oxidative Coupling‐Reaction of Xanthenes with Enaminones

“…[8] In view of the wide application of xanthenes, many methods have been developed to realize the construction of xanthene derivatives, especially some synthetic methods to 9-substituted xanthenes. [8][9][10][11] For example, Klussmann reported the oxidative coupling reaction of xanthenes with ketones, which required methanesulfonic acid as the only catalyst and elemental oxygen as oxidant, implementing a simple method to modify xanthenes at 9position (Scheme 1, eq 1). [10] Chen and co-workers described a catalyst-free direct C(sp 3 )À H sulfenylation of xanthene derivatives by using air as oxidant, providing an effective approach to 9-sulfenylated xanthenes with good functional group compatibility (Scheme 1, eq 2).…”

Synthesis of Antiviral Tetrahydrocarbazole Derivatives by Photochemical and Acid-catalyzed C-H Functionalization via Intermediate Peroxides (CHIPS)

“…In some cases, for example diethyl ether, hydroperoxides formed in air can also be explosive. Recently, we discovered a reaction that utilizes an autoxidation to form a new C-C bond from C-H bonds without need of a redox-active catalyst 13,14 . Simply stirring the substrates under oxygen in the presence of an acid catalyst leads to the formation of the new products.…”