Copper-Catalyzed Intramolecular C−H Oxidation/Acylation of Formyl-N-arylformamides Leading to Indoline-2,3-diones

Abstract

A new, efficient Cu-catalyzed intramolecular C-H oxidation/acylation method has been developed for the synthesis of substituted indoline-2,3-diones (isatins). In the presence of CuCl(2) and O(2), a variety of formyl-N-arylformamides underwent the tandem reaction to afford the corresponding indoline-2,3-diones in moderate to good yields. It is noteworthy that the reaction serves as the first example of transition-metal-catalyzed transformation for the preparation of indoline-2,3-diones.

Aerobic Copper-Catalyzed Organic Reactions

“…439 The method employs catalytic CuCl 2 under oxygen to induce coupling of aldehyde with the ortho -aryl position, providing an array of indoline-2,3-diones (isatins) in good to excellent yield (Scheme 216). Secondary amides failed to provide more than trace amounts of product, and substrates with strongly electron-withdrawing group at the para -position also gave poor yields.…”

Acylation of (Hetero)Arenes through CH Activation with Aroyl Surrogates

“…An intramolecular version for the acylation of arenes has also been developed. In 2010, Li and co‐workers reported a copper‐catalyzed intramolecular acylation of formyl‐ N ‐arylformamides to the corresponding indoline‐2,3‐diones 25. By using CuCl 2 as the catalyst and O 2 as the terminal oxidant, various substituted indoline‐2,3‐diones were produced in good yields with good functional group tolerance (Scheme ).…”

Cu‐Catalyzed Heterocycle Synthesis

“…The kinetic isotope effect (k H /k D = 2 : 4) was observed by FTIR (Fourier transform infrared spectroscopy) analysis, and this suggests that the C-H bond cleavage of aldehyde is the rate-limiting step for this transformation. A drawback of this transformation is the formation of inseparable regioisomers for meta-substituted substrates [74]. Fu et al developed a Cu(OAc) 2 -catalyzed synthesis of indoline-2,3-dione derivatives from readily available secondary anilines and ethyl glyoxalate in moderate to good yields (Scheme 8.37).…”