Indolones synthesis

Construction of the closely related NSAID bromefenac (46-8) depends on the Gassman indolone synthesis [46] for incorporation of the acetic acid chain. That reaction involves an anion-initiated electrocyclic rearrangement related conceptually to the little-known Hauser ortho substitution rearrangement. The simplest example of the latter depends on the formation of a carbanion by abstraction of one of the acidic protons from a benzyltrimethyl quaternary salt to give I (the... 

Merour J. Y., Piroelle S., Joseph B. Synthesis and Reactivity of lH-Indol-3(2H)-One and Related Compounds Trends Heterocycl. Chem. 1997 J 115-126 Keywords inverse electron-demand Diels-Alder reaction, indolone... 

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>. 

Ring expansion of 4J5>6,7-tetrahydro-4-indolone oximes also underpinned the synthesis of the 3//-azeto[l,2-a]pyrrolo[3,2-c]azepin-8-ones 30 (eg. R = H, Me) in good yield <00H(53)557>. 

An ingenious multi-step synthesis of oxo[l,3]thiazolo[5,4-/]azocine 214 is based on the transformations of ethyl tetrahydro[l,3]benzothiazolyl acetate 209 (81CPB1780 Scheme 59). Under the action of methylamine, 209 cyclizes to thiazolo[4,5-e]indolone 210 which, through compounds 211 and 212, converts into quaternary salt 213. The key stage of the process is the efficient rearrangement of this salt into thiazoloazocine under the action of alcoholic base. 

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... 

Other ring contractions that give azapentalene derivatives include the rearrangement of a fused oxazine to a pyrazolo[l,5-a]indol-4-one with acetic anhydride,165 and an interesting photochemical contraction of a cyclic lactone, which produces an isomeric fused indolone by a mechanism thought to involve the first meta photo-Fries rearrangement [Eq. (19)].166 The product was used as an intermediate for the synthesis of mitomycin antibiotics (Section VI,A). 

Indolizine chemistry, advances in, 23, 103 Indolones, isalogens and. 22, 123 lndoxazenes. 8, 277 29, 1 Isatin, chemistry of, 18, I Isalogens and indolones, 22, 123 Isatoic anhydrides, uses in heterocyclic synthesis, 28, 127... 

This enaminone cyclization route to indolones has been applied [76-79] for the synthesis of a variety of aspidospermidine class of alkaloids 153-155 from compound 152, which was obtained in very high yield from the photolysis of 151, as illustrated in Scheme 8.44. 

The synthesis of a structurally somewhat more complex indolone tyrosine kinase inhibitor starts with the construction of the pyrrole ring. Reaction of tert-butyl acetoacetate (87) with nitrous acid leads to nitrosa-tion on the activated methylene carbon. This reaction introduces the nitrogen atom that will appear in the target pyrrole. Condensation of 88 with... 

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