Cyclization of indoles

Wender and Aube have independently described the use of the Bischler-Napieralski reaction in the synthesis of Yohimban alkaloids. Aube s approach involved the cyclization of indole 50 followed by reduction of the resulting dihydroisoquinoline... 

Derivatives of y-carbolines were also sucessfully obtained by cyclization of indole oxime derivatives. Refluxing of oximes 308 in xylene gave the y-carbolines 309 in 51-55% yields (equation 133). ... 

Several examples of the cyclization of indole derivatives with alkenic side chains in the 3-position have been reported.6 In these examples, palladium chloride in combination with silver tetrafluoroborate is the cyclizing agent. The palladium tetrafluoroborate, presumably formed, should be a very reactive palladating species and probably is the reason why these reactions proceed at room temperature, although the mechanism is not yet completely clear. These reactions were worked up reductively (by addition of sodium borohydride) in order to reduce the expected alkenic product or any relatively stable organopalladium complexes that may have been formed (equation 4).6... 

Remarkably, sulfur acted as the electrophile in the conversion of sulfide 225 to the fused carbazole 226 (Equation 17) <2003S1191 >. A similar sulfur-mediated radical cyclization of indole derivatives is also known <20040L819>. 

PPA/phosphorus pentoxide (P2OS) cyclization of indole 414 provides azepino[3,4-7]indole-l,5-dione 415 in 86% yield as a precursor for azepino[3,4-7]indol-5-yl trifluoromethanesulfonate, the key intermediate in design of 5-substituted azepino[3,4-3]indol-l-ones (Equation 99) <2000T4491>. 

Feldman, K. S., Vidulova, D. B. Extending Pummerer Reaction Chemistry. Application to the Oxidative Cyclization of Indole Derivatives. 

Scheme I. Early examples of oxidative cyclization of indoles...

Cyclization of indol-2-yl acyclo C-nucleosides that carry acid-sensitive... 

Scheme 40 Beccalli s chemoselective cyclization of indole carboxamide derivatives...

In 2003, Beccalli et al. reported an intramolecular variant, allowing chemoselective cyclization of indole carboxamide derivatives into (3-carbolinones (path A) or pyrazino[l,2-a]indoles (path B) (Scheme 40) [68]. The chemoselectivity of the cyclization could be controlled by the reaction conditions. PdCl2(MeCN)2 and benzoquinone in DMF/THF made possible C-H functionalization at the C3 position of indole, whilst Pd(OAc)2 in Na2CC>3 and -Bu4XC1 in DMF resulted in intramolecular amination of the double bond (N-H functionalization). 

Stoltz et al. also reported an intramolecular reaction where C-H bond cyclization of indoles onto unactivated olefins was possible using palladium(II) and molecular oxygen as the sole stoichiometric oxidant (Scheme 41) [69]. They found the C2... 

Cyclization of indol-2-yl acyclo C-nucleosides that carry acid-sensitive O-protective groups such as 11 has been successfully achieved without affecting these groups by dehydration with triphenylphosphine-diethyl azodicarboxylate-iodine a mixture of anomeric C-nucleosides (12) was usually produced [94CL265 95JAP(K)95/118268] (Scheme 4). 

Feldman KS, Vidulova DB (2004) Extending Pummerer reaction chemistry. Application to the oxidative cyclization of indole derivatives. Org Lett 6 1869-1871... 

Gross S, Reissig H-U (2003) Novel stereoselective syntheses of highly functionalized benzannulated pyrrolizidines and indolizidines by samarium diiodide induced cyclizations of indole derivatives. Org Lett 5 4305 307... 

An exciting new development of oxidative cyclization of pyrroles emerged from Baran s Laboratories at Scripps Research Institute. Building on their success with the oxidative cyclization of indoles, Baran et al. expanded the... 

Beccalli and coworkers [51] described a similar oxidative cyclization of indoles using catalytic palladium and benzoquinone as the stoichiometric reoxidant (Scheme 9.22). By... 

Broggini, G. and Zoni, C. (2003) Regioselectivity on the palladium-catalyzed intramolecular cyclization of indole derivatives. J. Org. Chem., 68,7625-S. 

Electron-rich heteroaromatics may also act as the nucleophile (Scheme 6.58). ° The platinum-catalysed cyclization of indole 6.165 proceeds through intramolecular attack of the heterocycle on the rf-complex... 

Pyrroloindolines 33 are associated with a diverse family of structurally complex polyindoline alkaloids endowed with interesting biological activities. Macmillan and Zhu reported an enantioselective tandem arylation-cyclization of indole acetamides 32 and diaryliodonium salts in the presence of Cu(I) to obtain pyrroloindolines 33. This rapid protocol provides a new strategy for the enantioselective synthesis of various pyrroloindolines (Scheme 3) [19]. 

Cui and coworkers reported a Rh(III)-catalyzed C-H activation/cyclization of indoles and pyrroles at the C2 position with various alkyne and alkene substrates to give pyrimidin-2(l//)-ones and 3,4-dihydropyrimidin-2(l//)-ones 101 (Eq. (5.98)) [51]. The reaction tolerates a wide range of substituents on the aromatic rings. Moreover, both symmetrical and unsymmetrical alkynes/alkenes with various functional groups, such as hydroxyl, nitrile, and ester, also react efficiently to provide the expected JV-heterocycles in good to excellent yields. 

Beccalli EM, Bemasconi A, Borsini E, Broggini G, Riga-monti M, Zecchi G. Tunable Pd-catalyzed cyclization of indole-2-carboxylic acid allenamides carboamination vj. 

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