3-methyl-3-aryl oxindoles

The first example of direct enantioselective addition of a C—H bond to a ketone was reported by Shibata and co-workers in 2009 using the cationic Ir/ (S)-Hg-BINAP as the catalyst in the synthesis of a chiral 4-acetyl-3-hydroxy-3-methyl-2-oxindole with 72% ee. Recently, Yamamoto and co-workers developed a cationic Ir/(R,R)-Me-BIPAM catalyzed asymmetric intramolecular direct hydroarylation of a-keto amides 178 affording the chiral 3-substi-tuted 3-hydroxy-2-oxindoles 179 in high yields with complete regioselectivity and high enantioselectivity (84-98% ee). In their proposed reaction mechanism, the aryl iridium complex formed via C—H bond activation is coordinated with the two carbonyl groups of the amide (Scheme 5.65). 

When reacted with dimethyl acetylenedicarboxylate, the amines produced ben-zotriazolylaminobutendioates 188 accompanied by A-benzotriazolyl substituted 2-pyridones only in the case of 5-amino-2-methyl-2//-benzotriazole, the triazolo-9,10-dihydrobenzo[d]azepine and an unusual cyclization product, triazolo-2-oxindole (convertible into 2-methyltriazolo[4,5-/]carbostyril-9-carboxylate) were formed. The quinolones 189 were aromatized to chloroesters 190 these in turn were hydrolyzed to chloroacids 191 and decarboxylated to 9-chlorotriazolo[4, 5-/]quinolines 192 (Scheme 58) (93H259). The chlorine atom could be replaced with 17 various secondary amines to give the corresponding 9-aminoalkyl(aryl) derivatives 193, some of which exhibit both cell selectivity and tumor growth inhibition activity at concentrations between 10 and 10 " M (95FA47). 

In the diaryl amine series 191 (Scheme 47), additional, synthetically valuable, anionic pathways provide routes to anthranilates 190, oxindoles 192, and dibenzazepinones 194. Although not explored in terms of its scope [75c], the lateral metalation-cydization, 191 -> 192, is extensively precedented [69] but harbors intriguing potential for subsequent DreM chemistry. The rearrangement 191 —> 190 is an N —> ortho C anionic Fries equivalent of the aryl O-carbamate migration (Scheme 3E) [75c] and after N-methylation, 190 may be transformed into 1,2,3-trisubstituted systems 193 [76]. In another appealing manifestation of CIPE, the efficient conversion of 191 into dibenzazepinone 194 has been applied in an effective synthesis of the antiepileptic drug oxcarbazepine (Trileptal ) 195 [77] and may also be... 

The group of Wu reported that the CDC reaction between aryl methyl ketones and electron-rich arenes, such as aniline derivatives, can be promoted by I2 and CF3SO3H to afford ot,ot-diarylketones 96 (Scheme 8.46)." The combination of I2 and BuOK is effective for producing oxindole derivatives (97) (Scheme 8.47). A radical process by I2 is expected as one of the... 

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