Metal‐Free Catalyzed Cyclization of N‐Methoxybenzamides to Construct Quaternary Carbon‐Containing Isoindolinones

Abstract

Quaternary carbe | Density functional theory | Annulation | Alkynes | Synthetic methods Through the intramolecular cyclization of N-methoxybenzamides, a simple and efficient method for constructing valuable isoindolinones under metal-free conditions was developed. The reaction was featured by employing low-cost catalyst, simple operation, 100% atomic economy and excellent regioselectivity. Moreover, a detailed computational study on the reaction system has been performed to clarify the mechanism. This protocol tolerated a variety of functional groups and provided a metal-free protocol for the synthesis of chromane-or tetrahydroquinoline-fused isoindolinones in good yields.

Recent advances in ligand-enabled palladium-catalyzed divergent synthesis

“…Although various catalytic methods have been established for the synthesis of isoindolinone, 13 there is still a lack of methods for the synthesis of biisoindolinones. In 1997, Shim and co-workers introduced a novel carbonylative cyclization reaction to produce biisoindolinone.…”

Transition metal-free advanced synthetic approaches for isoindolinones and their fused analogues

“…10 Herein, we are interested in the synthetic pathways for isoindolinones and their fused analogues from available starting materials that do not contain any isoindolinone scaffolds in the initial step. Although there is a greater number of reports available on transition-metal catalyzed reactions 11 a – g via the reduction of the number of reaction steps to obtain the most available isoindolinone-based structures, transition metal-free protocols 12–53 offer various advantages over transformations involving transition metal catalysts. Transition metal-catalyzed protocols have the following drawbacks: (a) most metals are very sensitive to air and moisture, (b) toxic metals can easily mixed with drainage water during work-up, and (c) the high cost of metal catalysts is another barrier in the pharmaceutical industry.…”

“…This one-pot single catalyst via a series of reactions furnished chromane-fused isoindolinones from the substrate N -methoxy-3-((3-arenylprop-2-yn-1-yl)oxy)benzamide 141 (Scheme 39). 47 Different Lewis acid catalysts such as zinc, copper, scandium, indium and ytterbium salt were used for the cascade transformation, but 20 mol% of triflimide (HNTf 2 ) in DCE solvent at 100 °C was the optimum condition for the formation of product 142 . N -Methoxybenzamide with electron-withdrawing groups –F, –Cl, –Br and CF 3 was found to produce lower yields compared with an electron-donating substituent in the aryl ring at the alkyne substituent.…”