Indole-4,7-diones, synthesis

A concise method for the synthesis of the 5-substituted azepino[3,4-b]indol-l-ones 37 (eg. R = Bn, R1 = Ph) has been described, based on the Pd-mediated cross coupling reactions of azepino[3,4-b]indol-5-yl trifluoromethanesulfonates eg. 36. These latter compounds were accessed in turn from the corresponding azepino[3,4-i>]indole-l,5-dione <00T4491>. 

Construction of the indole ring via Fischer synthesis. Starting from a variety of 3,4-dihydro-lH-benzo[l ]azepine-2,5-diones 40 and arylhydrazines Fischer syntheses of indolo benzazepinones 41 have been reported (Scheme 8 (1999JMC2909)). Usually, the reaction comprises a two-step one-pot procedure with the formation of intermediate arylhydrazones in warm acetic acid followed... 

Combes synthesis with pentan-2,4-dione that led to 157, was ascribed to unfavorable steric hindrance in the alternative orientation in the Combes synthesis. 2-Amino-l,4-dimethylcarbazole underwent the Skraup reaction in the only orientation available to it. Finally, the carbazol-1-yIhydrazone of ethyl pyruvate underwent normal Fischer indolization giving 158 its 3-isomer gave an indole by cyclization at C-4 producing 159. ... 

Table 18 Synthesis of cyclohepta-, cycloocta-, and cyclonona[fa]-indole-1,3-diones...

Joshi et al. [81] have incorporated azetidin-2-one moiety into indole nucleus and synthesized several fluorine containing spiro-(3-lactams (Scheme 9). The synthesis involved the condensation of primary amines with an appropriate indole-2,3-dione... 

Bcnzofuran-4,7-dioncs have been synthesized regioselectively by [3 + 2] photoaddition of 2-hydroxy-1,4-benzoquinones with a range of alkenes (equation 185)664. The reaction occurs in 30-60% yield and is a useful method for the synthesis of the benzofuran ring system, which is important in natural products like acamelin665. Substituted naphthoquinones may also be used in this reaction666,667 and this has lead to a very simple two-step synthesis of maturinone. In a similar reaction, a [3 + 2] photoaddition reaction of 2-amino-1,4-naphthoquinones with electron-rich alkenes gave 13-82% yields of 2,3-dihydro-177-bcn/ /]indole-4,9-diones in a single-step process which involved photolysis followed by oxidation (equation 186)668,669. 

As part of a programme of studies on the synthesis of mitomycins, the dione 1 was treated with sodium hydride in dry THF at room temperature. This gave an epimeric mixture of carbinolamines which was highly acid sensitive and which, on treatment with glacial acetic acid at room temperature for 5 minutes, underwent dehydration to the tricyclic indole derivative 2. 

The result was confirmed by a second synthesis. The dimethylated C ring was built onto indole by condensation of hexane-2,5-dione with the reactive indolic 2,3 positions. Formylation of the resulting 1,4-dimethyl-carbazole (CCLXXXVIII) with X-methylformanilide proceeded preferentially in the 3-position to give the aldehyde CCLXXXIX whose... 

Isatin (lH-indole-2,3-dione) is a synthetically versatile substrate, where it can be used for the synthesis of a large variety of heterocyclic compounds, such as indoles and quinolines, and as a raw material for drug synthesis. Isatin has also been found in mammalian tissues, and its function as a modulator of biochemical processes has been the subject of several discussions. The advances in the use of isatin for organic synthesis during the last twenty-five years, as well as a survey of its biological and pharmacological properties are reported in this review and in the accompanying supplementary information. 

The Martinet procedure for the synthesis of indole-2,3-diones involves the reaction of an aminoaromatic compound and either an oxomalonate ester or its hydrate in the presence of an acid to yield a 3-(3-hydroxy-2-oxindole)carboxylic acid derivative which after oxidative decarboxylation yields the respective isatin. This method was applied with success for the synthesis of 5,6-dimethoxyisatin from 4-aminoveratrole whereas the use of 2,4-dimethoxyaniline was less successful40 (Scheme 9). 

Dandia A, Singh R, Khaturia S et al (2006) Efficient microwave enhanced regioselective synthesis of a series of benzimidazolyl/triazolyl spiro [indole-thiazolidinones] as potent antifungal agents and crystal structure of spiro[3H-indole-3, 20-thiazolidine]-30(l, 2, 4-triazol-3-yl)- 2, 40(lH)-dione. Bioorg Med Chem 14 2409-2417... 

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