Substitution oxindoles

Makosza et al.115 have also reported similar reactions with a 3-substituted oxindol and an aryl halide. The reaction occurs only if the aryl halide is activated by an electron-withdrawing substituent. 

Microwave flash heating was successfully employed in another palladium catalyzed two-step process leading to N-substituted oxindoles [32]. The... 

Scheme 10 Preparation of AT-substituted oxindoles via a condensation-arylation sequence...

Turner and Poondra have described an efficient intramolecular one-pot and two-step Goldberg aryl amidation that gives access to useful AT-substituted oxindoles (Scheme 29) [96]. 

Scheme 29 A two-step preparation of substituted oxindoles via transient amide formation...

Simple 2- and 3-halogenoindoles are generally stable in basic media but are readily converted into oxindoles by aqueous acids. Also, during the halogenation of indoles, 2-(3-indolyl)indoles are common by-products. The formation of both the oxindoles and the bisindoles involves protonation of the halogenoindole at the 3-position, followed by nucleophilic attack at the 2-position of the 3H-indolium cation and the subsequent elimination of the halogen acid (see Section 3.05.1.2.4). The formation of 2-(2-indolyl)indoles during the conversion of 3-substituted oxindoles into 3-substituted 2-chloroindoles has also been shown to result from the Lewis acid-catalyzed reaction of the 3-substituted 2-chloroindoles with 3-substituted indoles 81H(16)1441>. 

Another method of building up the physostigmine ring system was devised by the same authors who devised the first (35). In this method, the pyrrolo ring was closed by reaction of an appropriately amino-substituted oxindole (XV) with phosphorus pentoxide to yield the cyclic amidine XVI, which was subsequently reduced to XVII and then methylated to give a product claimed to be dl-esermethole (characterized as the methopicrate). 

Isatin-2,3-thiosemicarbazone is said to be produced only from isatin-2-thiosemicarbazone and thiosemicarbazine direct reaction of isatin with an excess of thiosemicarbazine gives only the C-3 substituted oxindole. The isatin-2,3-thiosemicarbazone cyclizes to a thiotriazinoindole derivative when heated280 (Scheme 59). 

Cyclization of the anilide 213 using TiCU produced the 3-chloro-substituted oxindole 214 (Equation 69), whereas a similar reaction induced by BF3-OEt2 gave the corresponding methoxy-substituted derivative <1998T4889>. Lewis acids have also been used in an approach to indole-2-carboxylates based on cyclization of (Z)-A(A -dimethyl-aminopropenoates derived by exposure of A -arylglycinates to DMEDMA <2006SL749>. 

Stolid, R., N-substituted oxindoles and isatins. J. Prakt. Chem. 105, 137-148 (1922). 

Vinca erecta contains vineridine N-oxide and two stereoisomers of majdine, which are all methoxy-substituted oxindole analogues of heteroyohimbine alkaloids. ... 

An efficient intramolecular, one-pot, two-step, Goldberg aryl amidation producing useful N-substituted oxindoles was recently described by Turner and Poondra (Scheme 15.61) [126]. 

A versatile route to N-substituted oxindoles has been developed by extending the utility of dilithiated o-alkylanilines. Treatment of N-alkyl-2-methylaniline with one equiv, of n-butyllithium, followed by COj and then a second equiv. of n-butyllithium gave a dilithiated intermediate which reacted with CO to give an oxindole. <94H(37)701> The method was applied to several ring-substituted oxindoles and to 5- and 7-aza-oxindoles. 

Recent syntheses of indol-2-ones (oxindoles) include Chuang s p-toluenesulfo-nyl radical induced cyclization of allylsulfones and the oxidative free-radical reactions of a,a-dimethylsulfonyl substituted anilides [62], the tin-free synthesis of 3-aminoindolinones from O-benzyl oxime substituted amidocyclohexadienes [63], and Pudlo s 5-exo-trigl5-exo-trig tandem radical cyclization of acrylamides to give 3-pyrrolidinone substituted oxindoles, shown below [64]. 

Given the variety of methods for accessing 3-alkyl or 3-aryl oxindoles in racemic form, the direct asymmetric hydroxylation of 3-substituted oxindoles represents a conceptually appealing strategy for controlled installation of hydroxyl-bound... 

The Barbas group has employed a cinchona alkaloid to direct an enantioselective a-amination of oxindoles using diethyl azodicarboxylate as the electrophilic species (Scheme 27) [61]. In one example, A-benzyl protected 3-methyloxindole 100 was transformed to the amino-substituted oxindole 102 in 91% ee using (DHQD)2PHAL... 

Liu ZW, Yang TT, Wang WJ, Li GQ, Tang BQ, Zhang QW, et al. Ervahainine A, a new cyano-substituted oxindole alkaloid from Ervatamia hainanensis. Tetrahedron Lett 2013 54(48) 6498-500. 

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