Indoles vinyl

Nitro-vinyl)-indol —> 2-(2-Nitro-alhyl)-indol 30"/, d.Th. 

Guertler et al. (1996) described a wide range of cycloaddition reaction between 2-vinyl indoles acting as heterodienes and cyclic or acyclic enamines bearing acceptor groups in (3 positions. The reaction was induced by the formation of 2-vinylindole cation-radicals through anodic oxidation. The synthesis of 4a-carbomethoxy-6-cyano-5,7-dimethylindolo[l,2-a]-l,2,3,4,4a,12a-hexahydro-1,8-naphthyridine can serve as an example (Scheme 7.24). 

Blechert and co-workers successfully employed the [4 -I- 2] cycloaddition for the transformation of indole derivatives [79-81], For instance, using 2-vinyl-indole derivatives as heterodienes, (3-acceptor-substituted cyclic and acyclic ena-mines (dienophile), and triarylpyrylium tetrafluoroborate as the photosensitizer, the corresponding Diels-Alder adducts were formed in moderate to good yields with complete regiochemical and stereochemical control [79], Alternatively, good results could be obtained in the reaction of indoles and exocyclic 1,3-dienes, thus providing an easy excess to multifunctionalized carbazoles [80], Quantum... 

The use of RCM in the synthesis of 3,4-carbocyclic indoles was reported by Perez-Castells and co-workers as is exemplified in Scheme 29 <02T5407>. Vinyl indole 49 was quatemized with BnBr and quaternary salt underwent smooth addition of vinyl magnesium bromide to give the indole diene 50. RCM was accomplished with the MC2 in good yields. 

Blechert et al. have opened a very elegant alternative to the classical hetero Diels-Alder methodology by generating the cationic radical 3-31 - which might be conceived as 1-aza-1,3-butadiene - from the 2-vinyl indole 3-30 by means of a single electron transfer process. In the presence of the tetrahydropyridine derivative 3-32 the radicalic intermediate was transformed into the tetracyclic compound 3-33 which contains the complete skeleton of the alkaloid gonio-mitine [250, 251]. The authors have postulated a stepwise mechanism for this [4+2] process, therefore it should be understood as a formal hetero Diels-Alder reaction (Fig. 3-11). 

The hydroxyl group in XXXV could not be acetylated instead, the iV-vinyl indole, the apo compound, XXXVIII was obtained. In fact, simple heating or solution of the alkaloid in strong acid was all that was necessary. The latter experiment, which finds an analogy in eburnamine itself, required the intermediacy of the iminium form (see Chart II). This iminium form was apparently stable in strong acid, since vincamine in 11 N hydrochloric acid had a UV-spectrum with a long wavelength maximum at 360 mp (log e = 3.85) compatible with XXXIX which reverted irreversibly into apovincamine (XXXVIII R = H) upon dilution (18). 

AWittig reaction was used to obtain 2-vinyl indoles 1291 (Equation 285) <2002S1810>. The ylide was generated from methyltriphenylphosphonium bromide in anhydrous THE under argon using KHMDS in toluene at room temperature for 0.5 h and then was cannulated to a solution of aldehyde 1290. These conditions were essential to obtain high yields. 

Research by B. Jiang et al. showed that the asymmetric aminohydroxyiation of vinyl indoles can afford (S)-A/-Boc protected a-indol-3-ylglycinols in moderate to good yield and with up to 94% ee. The use of these enantiopure intermediates allowed the short enantioselective total synthesis of bisindole alkaloids, such as dragmacidin A, which contains a piperazine moiety between the indole rings. 

Yang, C.-G., Wang, J., Tang, X.-X., Jiang, B. Asymmetric aminohydroxylation of vinyl indoles a short enantioselective synthesis of the bisindole alkaloids dihydrohamacanthin A and dragmacidin A. Tetrahedron Asymmetry 2002, 13, 383-394. 

This sequence can be used to build polycyclic heterocycles very quickly from simple starting materials. Even enolisable aldehydes with extra functionality such as 201 can be used in the sequence the more complex vinyl indole 202 is formed in very reasonable yield25 (66%). 

Utilising tri-n-butylphosphine to displace the dimethylamino group generates, in situ, a zwitterion which, by proton transfer, becomes a Wittig intermediate and thus can be utilised to prepare 3-vinyl-indoles. ... 

Wird 2-[l-Cyan-2-pyridyl-(3)-vinyl]-indol in Athanol in Gegenwart von Jod belichtet, so erhalt man Pyrido-carbazole, unter AusschluB von Oxidationsmitteln dagegen 3-VinyI-siibstitniertc Oarbazole2 ... 

Several groups have reported procedures for palladium-mediated cross-coupling of indoles. This can involve the indole reacting as the nucleophilic (eg. stannane, zinc or boronic acid derivatives) or electrophilic (halide or triflate) component. The variety of such procedures that are now available indicates that Pd-catalyzed cross-coupling is the most versatile method for synthesis of many aryl and vinyl indoles. 

Synthetic routes to vinylpyrroles and vinyl indoles continue to be of interest because of their potential as Diels-Alder dienes. Work by Settambolo and coworkers demonstrated that 3-acyl-l-p-toluenesulfonylpyrroles can be converted to 3-vinylpyrroles by standard methods such as Wittig olefination or organometallic addition followed by dehydration. <94G173> The tosyl group can be removed by alkaline hydrolysis. 

There have been additional studies on the synthesis of carbazoles from vinyl indoles by Diels-Alder cycloaddition. 3-(l-Methoxyvinyl)indoles can be generated in situ by deprotonation of salts of 3-(l-methoxyalkylidene)indolenines. These salts are prepared... 

Some highly substituted carbazoles were obtained by photo-induced Diels-Alder reactions of 2-(l-cyano-vinyl)indoles using stabilized enamines as dienophiles. <94SL141>... 

Blechert and coworkers have developed a very efficient one-pot synthesis of 2-vinylindole derivatives, starting from an aldehyde, phenyUiydroxylamine, and cyanoallene [64], These 2-vinyl indole species have demonstrated good synthetic utility in constructing linear carbazole skeletons that could be useful as key intermediates in the assembly of indole alkaloids [65]. Early on, it was discovered that the Diels-Alder reactions of the 2-vinylindole species 150 did not proceed under thermal conditions, and the use of Lewis acids did not offer any advantages. However, cycloadditions with electron-deficient dienophiles 151 (at room temperature in chloroform/dichloromethane and in the presence of trifluoroacetic acid), followed by aromatization, led to the formation of the tetrahydrocarbazole structures 152 (Scheme 38). These reactions were found to proceed with high selectivity for the endo products. The tetrahydrocarbazoles 152 could then be oxidized with DDQ to form the corresponding carbazoles in good yields. 

The use of 2-vinylindole species has played a large role in the total synthesis of the pentacyclic Aspidosperma alkaloids. In 1978, Kuehne reported an elegant synthesis of DL-vincadifformine (182) that featured as a key step the reaction of an indoloa-zepine 177 with the bromoaldehyde 178, thus leading to the in situ formation of 2-vinylindole species 181, which in turn underwent an intramolecular Diels-Alder reaction to provide 182 [71] (Scheme 42). Kuehne and others have used this same methodology, using the in situ generation of a 2-vinyl indole, followed by an intramolecular Diels-Alder reaction, to synthesize a number of Aspidosperma alkaloids and their analogs [72]. 

Fayol A, Fang Y-Q et al (2006) Synthesis of 2-vinylic indoles and derivatives via a Pd-catalyzed tandem coupling reaction. Org Lett 8 4203-4206... 

Bleile M, Otto H-H (2005) Substituted pyrrolo[3,4-a]carbazoles from reactions between 3-(l-methoxy-vinyl)indoles and maleimides. Monatsh Chem 136 1799-1809... 

Grieco PA, Kaufman MD (1999) Intramolecular imino Diels-Alder reaction of a 3-vinyl indole application to a total synthesis of (+-)-ebumamonine. J Org Chem... 

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