Indolones, reaction with

N-Methyl-4-hydroxy-2-quinolone 183 in a three-component reaction gives spiro pyrano[3,2-c]qionoline-2-ones (02MI2), but indolones 213 with 4-hydroxy-6-methyl-2-pyridone 177 react in a complicated way (97BCJ1625). Ethoxycarbonyl-methylene indolone (Z = COOEt) forms pyrans 224, while dicyano analogs (Z = CN) yield substituted quinoline 225 (Scheme 85). 

The indolone 160 in a Diels-Alder reaction with cyclopentadiene at 20°C in the presence of aluminum chloride or perchloric acid gave 161.98... 

Indolones such as (40) have been exploited on a few occasions as heterodienophiles (equation 12). Cycloaddition of (40 R = Ph) with several dienes was regioselective (cf. equation 12). The reactions with ( ,Z)- and ( , )-2,4-hexadiene were syn stereoselective with respect to the diene but exolendo selectivity was not determined. With the related dienophile (40 R = C02Et), regioselectivity deteriorated in the cycloadditions. 

According to Pitacco, Valentin and coworkers secondary ketoenamines react generally with nitroolehns to give alkyl- and aryl-substituted tetrahydroindole-7-ones under thermodynamic control in good yield without any catalyst, if the a-ketoenamine is an N-alkyl derivative. The course of the reaction depends on the substituents and the conditions which result in different cleavage or rearrangement reactions. In the case of a-nitrostilbene a Michael adduct is obtained in low yield. If, however, for example, 1-nitrocyclopentene is used in the reaction with iV-t-butylenaminone under kinetic control, an unstable [4 -i- 2]cycloadduct can be isolated. The reaction clearly demonstrates the concurrence of Michael addition and subsequent cyclization to 7-indolones... 

In a recent synthesis of tryptanthrin, one step consisted of annulating the carbonyl group of 2-indolone to its C-3 atom by reaction with isatoic anhydride (review [3008]) in the presence of tetramethylethylenediamine (TMEDA). 

In the scale up effort of 5,6-disubstituted benz[cc/]indolones 42, a precursor for inhibitors of thymidylate synthase, the Lessen rearrangement was utilized as the key step. A-hydroxylnaphthalimide 38 was converted to activated hydroxamate 40 through aromatic nucleophilic substitution reaction with 39. The Lessen precursor 40 then xmderwent conversion to amino acid intermediate 41, which was subsequently transformed to lactam 42 under acidic conditions. ... 

The sulfur analogue of the Hauser ortho-substitution rearrangement provides access to an arylacet-ic NSAID. Reaction of the aminobenzophenone 176 with ethyl methylthioacetate and tert-butyl hypochlorite gives the intermediate 178. The reaction probably proceeds by way of formation of the S-chlorinated sulfonium derivative 177 displacement on sulfur will lead to the salt 178. Treatment with triethylamine leads initially to the betaine 179. Electrocyelic rearrangement of that transient intermediate leads, after rearomatization, to the homoanthranilic acid 180. Internal ester-amine interchange leads then to indolone 181 [45]. The thiomethyl group is then removed with Raney niekel. Saponifieation of intermediate 182 affords bromfenac (183) [46J. 

Indolones and isoindolones have been utilised in the synthesis of fused azepine derivatives. In the one reaction, rearrangement of the alkynes 18 to 2-benzazepine-l,5-diones 19 in the presence of Lewis acids has been reported <96XL393>. Xhe yields vary from moderate to very good. Xricyclic azepines 20 are obtained by the reaction of the 4-[2 -(p-toluenesulfonyloxy)ethyl]-2-oxindole with imines <96JHC209>. 

The base-catalyzed reaction of 4-hydroxycoumarin 184 with indolones 213 or with isatin and MN 27a on short heating leads to spiro pyrano-benzopyrans 220 (89JHC1097, 05RCB992, 08JCO741, 08RCB2373) (Scheme 82). 

Similar results were obtained when diphenylnitrenium ion was trapped with various silylenol ethers and silyl ketene acetals (e.g., 116). In these experiments, a distribution of N-(117), p- (118), and o- (119) adducts were generated (Fig. 13.55). The ortho adducts underwent a cyclization reaction, producing an indolone derivative. 

An indolone comprises a prominent moiety in the dopamine D2 selective antipsychotic agent ziprasidone (32-8). Reduction of the ketonoid carbonyl group on the indoxyl (32-1) under Wolff-Kischner conditions affords the indolone (32-2). Acylation of the product with chloroacetyl chloride in the presence of aluminum chloride then affords the reactive chloroacetyl derivative (32-3). In a convergent sequence, reaction of isothiazolone (32-4) with phosphorus oxychloride leads to... 

The reaction of isatin cr-chloride (160a) with electron-rich aryl compounds, in the presence of a Lewis acid, gives indolone salts (161) from which the indolones (162) can be liberated on treatment with base.49, 108, 109 The reaction of 160a with various amines, under these conditions, has been reported108 to give the unstable indolones (163) although later attempts to repeat the synthesis were unsuccessful.49... 

The A-chloro compound 176, obtained from the corresponding meth-oxyamide with f-butyl hypochlorite, was cyclized to l-methoxy-2-indolone 163 by silver carbonate in trifluoroacetic acid (87% yield) (84JA5728), or by other silver or mercury salts (87T2577), and more conveniently by anhydrous zinc acetate in 1,2-dichloroethane (91% yield) (87CL1771). The reaction proceeds through the spiro intermediate 177, followed by both possible 1,2-shifts. 

After cooling the reaction mixture in an ice-bath, the inorganic salts were removed by filtration and washed with acetone. The combined filtrates were concentrated in vacuo. The residual syrup was diluted with saturated brine and extracted with three portions of diethyl ether. The gathered extracts were dried over anhydrous magnesium sulfate, clarified with charcoal and treated with ethereal hydrogen chloride until precipitation was complete. The solid was slurried in diethyl ether and decanted several times, filtered and air-dried to give 3.8 g (86%) of tan 4-(2-di-n-propylaminoethyl)-7-(l-phenyl-lH-tetrazol-5-yloxy)-2(3H)-indolone hydrochloride. Recrystallization from 200 cc of hot acetonitrile gave 2.6 g (59%) of microcrystalline product, m.p. 245°C. 

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