Indole-2,3-quinodimethane synthesis

Magnus PD, Sear NL. Indole-2,3-quinodimethanes Synthesis of selectively protected derivatives of the fused dimeric indole alkaloid staurosporinone. Tetrahedron. 1984 40 2795-2797. 

In a similar heterocyclic quinodimethane ring construction strategy, the hexacyclic adducts (64) were isolated in good yield upon condensation of appropriately functionalized indole imines with ( )-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid chloride (Equation (35)) (88JA2242). In a demonstration of the utility of this new method for indole alkaloid synthesis, further transformations conducted on compound (64 R = R2 = H, R3 = Et) were shown to lead to ( —)-16-methoxy-tabersonine. 

The isomeric pyranoindol-2-ones have also been used as relatively stable examples of indole quinodimethanes and offer a similar synthesis of carbazoles <90CC1667,90JCS(Pl)673,92JOC2105). An intramolecular version of this cycloaddition has been adapted to the synthesis of staurosporine derivatives and illustrates the synthetic process (Scheme 94). 

Terzidis M, Tsoleridis CA et al (2005) Chromone-3-carboxaldehydes in Diels-Alder reactions with indole-ortho-quinodimethane. Synthesis of tetrahydrochromeno[2, 3-b]carba-zoles. Tetrahedron Lett 46 7239-7242... 

Kinsman AC, Snieckus V (1999) Directed ortho metalation-cross coupling route to indolo-4, 5-quinodimethanes. Synthesis of benz[e]indoles. Tetrahedron Lett 40 2453-2456... 

This category corresponds to the construction of the carbocyclic ring by 2 + 4 cycloaddition with pyrrole-2,3-quinodimethane intermediates. Such reactions can be particularly useful in the synthesis of 5,6-disubstituted indoles. Although there are a few cases where a pyrrolequinodimethane intermediate is generated, the most useful procedures involve more stable surrogates. Both 1,5-di-hydropyrano[3,4-b]pyrrol-5(lf/)-ones[l] and l,6-dihyropyrano[4,3-b]pyrrol-6-(in)-ones[2] can serve as pyrrole-2,3-quinodimethane equivalents. The adducts undergo elimination of CO2. 

Synthesis of carbazoles from indoles by quinodimethane intermediates... 

Indole-2,3-quinodimethanes have also been exploited as the key intermediates in indolo[2,3-a]caibazole synthesis, allowing the preparation of several interesting systems. Thus, when the starting materials 74a-b (obtained from the condensation of protected indole-2-carboxaldehydes with 2-aminostyrene) underwent treatment with methyl chloroformate in hot chlorobenzene, the carbamates 75a-b were obtained, and could subsequently be dehydrogenated into the aromatic compounds 76a-b (Scheme 11). However, all functionalization attempts of the methyl... 

The reactive indolo-2,3-quinodimethanes are generated in situ generally from N-protected 2,3-disubstituted indoles (514,515). Generation of reactive indolo-2,3-quinodimethanes was achieved by fluoride-induced, 1,4-elimination of silylated indolyl ammonium salts, and was applied in the synthesis of substituted tetrahydrocarbazoles (516). Subsequently, the iodide-induced 1,4-elimination of ]V-benzoyl-2,3-bis(bromomethyl)indole (534) methodology was developed for the synthesis of reactive indolo-2,3-quinodimethanes and was applied for the first time in the synthesis of substituted carbazoles (e.g., 536) (517) (Scheme 5.14). 

Miki and Hachiken reported a total synthesis of murrayaquinone A (107) using 4-benzyl-l-ferf-butyldimethylsiloxy-4fT-furo[3,4-f>]indole (854) as an indolo-2,3-quinodimethane equivalent for the Diels-Alder reaction with methyl acrylate (624). 4-Benzyl-3,4-dihydro-lfT-furo[3,4-f>]indol-l-one (853), the precursor for the 4H-furo[3,4-f>]indole (854), was prepared in five steps and 30% overall yield starting from dimethyl indole-2,3-dicarboxylate (851). Alkaline hydrolysis of 851 followed by N-benzylation of the dicarboxylic acid with benzyl bromide and sodium hydride in DMF, and treatment of the corresponding l-benzylindole-2,3-dicarboxylic acid with trifluoroacetic anhydride (TFAA) gave the anhydride 852. Reduction of 852 with sodium borohydride, followed by lactonization of the intermediate 2-hydroxy-methylindole-3-carboxylic acid with l-methyl-2-chloropyridinium iodide, led to the lactone 853. The lactone 853 was transformed to 4-benzyl-l-ferf-butyldimethylsiloxy-4H-furo[3,4- 7]indole 854 by a base-induced silylation. Without isolation, the... 

In 1984, a facile synthesis of pyrrolo[3,4-/7]indole (5) as a stable indole-2,3-quinodimethane analogue using an intramolecular azide-alkene cycloaddition-cycloreversion strategy was reported (Scheme 9.2) (3). Treatment of bromo compound 3 with NaNs in aqueous tetrahydrofuran (THF) produced the triazoline 4 via an intramolecular 1,3-dipolar cycloaddition of an intermediate azide. Treatment of the triazoline 4 with p-toluenesulfonic acid (p-TSA) effected 1,3-dipolar cycloreversion of 4 to give pyrroloindole 5 in 82% yield along with diethyl diazomalonate. 

Indigo derivatives, synthesis and application of 88YGK681. Indole-2-carboxylic acid, chemistry of 87YGK1171. Indolo-2,3-quinodimethanes and their analogues in synthesis of [b]-annelated indoles 89CRV1681. 

Synthesis of indole alkaloids from indole-2,3-quinodimethanes 84ACR35. Synthesis of indole alkaloids, introduction of ethylidene substituent ... 

Magnus - Indole 2,3-quinodimethane strategy for synthesis of Indole alkaloids [84ACR35]... 

Many examples of Diels-Alder reactions have been carried out on quinodimethanes derived in a variety of ways from pyrrole and indole precursors. This area continues to be widely investigated because of its generality and its synthetic utility. In the case of pyrrole derivatives, this methodology leads to the synthesis of indoles, and particularly those substituted in the benzene ring. 

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