Indole ring formation

A novel indole ring formation involving DBU nucleophilic addition to 1,3,5-trinitrobenzene has appeared as shovm in Eq. 10.69. 

In a recent study, we showed that the more flexible pyrido[l,2-a]indole-based cyclopropyl quinone methide is not subject to the stereoelectronic effect.47 Scheme 7.17 shows an electrostatic potential map of the protonated cyclopropyl quinone methide with arrows indicating the two possible nucleophilic attack sites on the electron-deficient (blue-colored) cyclopropyl ring. The 13C label allows both nucleophile attack products, the pyrido[l,2-a]indole and azepino [l,2-a]indole, to be distinguished without isolation. The site of nucleophilic is under steric control with pyrido [1,2-a]indole ring formation favored by large nucleophiles. 

Finally, indole ring formation is via condensation of the amino and keto functions. This is analogous to imine formation, as seen in part (a), but dehydration produces the aromatic pyrrole ring rather than an imine. Alternatively, one could write imine formation followed by tautomerism to the aromatic enamine. 

Give a mechanism for the indole ring formation in step b. 

Other marine natural products with potent antitumour and antiviral activities, the eudistomins, continue to attract attention. As part of a new synthetic approach to the eudistomins, the stereoselective formation of the P-lactam fused oxathiazepine 110 has been reported <03SL738> C-N bond formation from 106 (via 105) was used to complete the seven-membered ring, and then this product 107 was converted into 110 via 108 and 109. Unfortunately, after ring opening the P-lactam in 110 and setting up the substituents for indole ring formation, this crucial indolisation was not successful. Other pathways are being explored but the P-lactam precursor concept is a clever one. 

Miyashita, K., Kondoh, K., Tsuchiya, K., Miyabe, H., Imanishi, T. Novel indole-ring formation by thermolysis of 2-(N-acylamino)benzylphosphonium salts. Effective synthesis of 2-trifluoromethylindoles. J. Chem. Soc., Perkin Trans. 11996, 1261-1268. 

Boger and coworkers reported the first total synthesis of chloropeptin II and later its transformation into chloropeptin I (2009JA16036). The key step to this total synthesis was macrocycHzation of peptide 31 by an intramolecular Larock indole heteroannulation. This intramolecular reaction between a substituted 2-bromoaniline with a removable terminal alkyne substituent afforded simultaneous regioselective indole ring formation and macrocycli-zation. The TES substituent of the alkyne dictates indole cyclization regio-selectivity (Scheme 20). 

As Table 8 illustrates, the venerable Japp-Klingemann variation of the Fischer indolization continues to attract interest. Entry 1 features a three-component Japp-Klingemann indolization involving diazonium salts, acid chlorides, and amines or alcohols and involving the intermediacy of a-hydrazono carboxylic acid esters and amides prior to indole ring formation [385]. Entry 2 describes a preparation of 5-indolyl-Mannich bases and, hence, an expedient source of 5-(chloromethyl)indoles (acetyl... 

The penultimate intermediate in many indole ring formations is an amino carbonyl gionp (aldehyde or ketone), which then gives the hydroxyindoline and, by dehydration. 

The reductive cyclization of o-nitrophenylacetaldehydes presents the obvious problem in that the formyl group is susceptible to reduction. Nevertheless, several such successful indole ring formations are known. Moreover, the intermediate hydroxylamine can cyclize onto the formyl group to give an A-hydroxyindole. 

In a third variation of a tin-mediated indole ring formation, Fukuyama used imidoyltellurides to afford 2,3-dialkylindoles (Scheme 5) [28],... 

The cycloaddilion of nitrosoarenes with alkynes as reported by Penoni and colleagues seems to involve a radical-mediated indole ring formation (Scheme 6, equations 1, 2) [32]. Other groups can be used to cap the labile A-hydroxyindoles (Boc, Bn, CO Et, Cbz, Ts, Bz). Li and colleagues have discovered a new synthesis of... 

Previous chapters presented examples of Pd-catalyzed carbon-hydrogen activation as a route to indole ring formation, and several new examples are presented here. Lu and coworkers effected C-H activation of A-arylamides and subsequent coupling with alkynes to give 2,3-disubsti-mted indoles (Scheme 3, equation 1) [33]. Similar indoles were synthesized by Cabrera and colleagues from a Pd-catalyzed direct combination of anilines and a-diketones (equation 2) [34], With 2,3-hexanedione, only 2-n-Pr-3-methyhndole was obtained (95%), and 4-methoxyaniline afforded 2,3-diphenyl-5-methoxyindole in lower yield... 

Iwasawa and coworkers discovered that mngsten penta-carbonyl facilitated indole ring formation from the appropriate aryl acetylenes (Scheme 1, equations 1 and 2) [1-3], The W(CO)j can be generated in situ by the irradiation of W(CO) in THF. The indolization in equation 2 is proposed to be a rare example of a 1,5-dipolar cycloaddition. Liang and colleagues observed that scandium triflate catalyzed the Friedel-Crafts cyclization of 5-(arylamino)pent-3-yn-2-ones to afford an array of indoles (equation 3) [4]. 

A key step in a synthesis of the carbazole alkaloid murraya-quinone-B (132) is the concomitant indole ring formation and regio-selective Claisen rearrangement from the azide (129), which on... 

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