Microwave-Assisted Sequential Amide Bond Formation and Intramolecular Amidation:  A Rapid Entry to Functionalized Oxindoles

Abstract

A general method has been developed for the synthesis of N-substituted oxindoles. The two-step process involves initial microwave-assisted amide bond formation between 2-halo-arylacetic acids and various alkylamines and anilines, followed by a palladium-catalyzed intramolecular amidation under aqueous conditions. In the case of alkylamines, the procedure can be carried out as a one-pot process without isolation of the intermediate amide. [structure: see text]

Biarylphosphanliganden in der palladiumkatalysierten Aminierung

“…[232] Die Gruppe von Turner verwendete die palladiumkatalysierte intramolekulare Amidierung zur Synthese von Oxindolen (Schema 63). [233] Bei diesem Verfahren wurde das [234] und gemäß van den Hoogenband benötigen entsprechende Oxindolbildungen mit XPhos unter herkömmli-chem Erhitzen ungefähr 3 h. [235,236] ) Die Mikrowellenbestrahlung wurde ferner von Zhu und Mitarbeitern bei einer Sequenz aus Ugi-Vierkomponentenreaktion und intramolekularer Amidierung eingesetzt, um Oxindole für diversitätsorientierte Synthesen zu erhalten (Schema 64). [237] Ebenfalls durch Mikrowellenbestrahlung verbesserten Wissenschaftler von Solvay den Zugang zu 3-Aminoöstron, einem Schlüsselintermediat in der Synthese biologisch aktiver Steroide (Schema 65).…”

Biaryl Phosphane Ligands in Palladium‐Catalyzed Amination

“…[232] Intramolecular amidation was used by Turner in a palladium-catalyzed synthesis of oxindoles (Scheme 63). [233] In this approach an amide was initially generated from from an amine and 2-haloarylacetic acid under solvent-free conditions with microwave heating. The crude product was then subjected to a palladium-XPhos catalyst system in order to effect the cyclization.…”

Copper powder-catalyzed chelation-assisted cascade reaction of o-chloroarylacetic acids with amines under solvent- and ligand-free conditions: synthesis of oxindoles

“…2g, 5 One of the most remarkable features is the pre-installation of a nitrogencontaining functional group on the precursors. Among them, the use of anilide derivatives is predominate in contemporary organic synthetic methodologies, whereas arylacetic acid derivatives are far less used.…”

“…2g, 5 The former two limit to the preparation of free NH oxindoles. The latter provides a powerful strategy for the construction of oxindoles functionalized at N-, C3-positions.…”

“…The latter provides a powerful strategy for the construction of oxindoles functionalized at N-, C3-positions. For instance, Turner's group has reported the access to oxindoles via sequential amide formation/palladium-catalyzed intramolecular amidation in two steps (Scheme 1a), 5 wherein the expensive noble metal catalyst, toxic phosphine ligand, and strong base are required besides the high temperature of 150 C. To our knowledge, the direct construction of oxindole scaffold by the introduction of amino group to the benzene ring of o-haloarylacetic acids, especially o-chloroarylacetic acids, is yet unexplored.…”