Indoles reaction with oxidizing agents

Beccalli et al. reported a new synthesis of staurosporinone (293) from 3-cyano-3-(lH-indol-3-yl)-2-oxo propionic acid ethyl ester (1464) (790). The reaction of 1464 with ethyl chlorocarbonate and triethylamine afforded the compound 1465, which, on treatment with dimethylamine, led to the corresponding hydroxy derivative 1466. The triflate 1467 was prepared from 1466 by reaction with trifluoromethanesulfonic anhydride (Tf20) in the presence of ethyldiisopropylamine. The palladium(O)-catalyzed cross-coupling of the triflate 1467 with the 3-(tributylstannyl)indole 1468 afforded the vinylindole 1469 in 89% yield. Deprotection of both nitrogen atoms with sodium ethoxide in ethanol to 1470, followed by photocyclization in the presence of iodine as the oxidizing agent provided the indolocarbazole 1471. Finally, reductive cyclization of 1471 with sodium borohydride-cobaltous chloride led to staurosporinone (293) in 40% yield (790) (Scheme 5.248). 

Owing to the susceptibility of indole, isoindole and pyrrole rings to oxidation (see Section 3.05.1.4) and acid-catalyzed dimerization and polymerization (see Section 3.05.1.2.2), the products of the reactions with nitrating and nitrosating agents are subject to the reaction conditions. 

Bis[4-methoxyphenyl] tellurium oxide was found to be a mild and highly selective oxidizing agent for the conversion of thiocarbonyl groups to carbonyl groups, thiols to disulfides, arylhydrazines to arenes, and 1,2- or 1,4-dihydroxyarenes to quinones. No reaction was observed with simple phenols, alcohols, enamines, amines (including pyrrole, indole, tryptophan, tyrosine, aniline, and dimethylaniline), oximes, dithiolanes, isonitriles, and 2,4-dinitrophenylhydrazones4. 

Indoxyl reacts further by radical coupling followed by oxidation to give indigo. Other oxidizing agents, as well as air, cause such reactions. On oxidation, indoles with substituents in the 3-position are converted into indol-2(3//)-ones (oxindoles) ... 

This reaction was first reported by Nenitzescu in 1929. It is the synthesis of a 5-hydroxyindoie derivative involving the condensation between a 1,4-benzoquinone and a /3-amino-a ,/3-unsaturated compound and subsequent cyclization. Therefore, this reaction is generally known as the Nenitzescu indole synthesis, Nenitzescu reaction, j or Nenitzescu synthesis.Occasionally, it is also referred to as the Nenitzescu cyclization, Nenitzescu condensation, s.2i qj. Nenitzescu process. It should be pointed out that the synthesized indole derivatives by this reaction are restricted to those with an electron-withdrawing group at position 3, such as an ester or a carbonyl group. In addition, the completion of this reaction requires an appropriate oxidizing agent to convert the initial adduct into the indole derivative. i From monosubstituted quinone, 4-, 6- and 7-substituted 5-hydroxyindole derivatives all are possible products, but 6-substituted isomer is the one normally obtained. ... 

Phenanthridinone derivatives have been reported to be found in a number of natural alkaloids and exhibit a wide range of biological activities. In the case of starting from bi-functionalized arenes with transition metal catalysts, the intramolecular cyclization of 2-bromo-iV-arylbenzamides via C-H activation is the most direct pathway, which has been applied in the synthesis of anti-hepatitis C virus agents and materials. Remarkably, Yao, Xu and their co-workers developed a one-pot procedure for the synthesis of a pyrrolophenanthridone skeleton via an intramolecular Heck reaction and oxidation of N-(2-bromobenzyl) substituted indoles. Moderate to good yields of the desired products were isolated in one step (Scheme 3.67). From the point view of academic interest, the... 

Utilizing an alternate mode of Diels-Alder reactivity, Harman has examined the cycloaddition reactions of 4,5-T -Os(II)pentaammine-3-vinylpyrrole complexes with suitably activated dienophiles <96JA7117>. For instance, cycloaddition of the p-vinylpyrrole complex 58 with 4-cyclopentene-l,3-dione, followed by DDQ oxidation affords 59, possessing the fused-ring indole skeleton of the marine cytotoxic agent, herbindole B. 

Dialkyl phosphites such as 49 (Scheme 9) have been reacted as nucleophiles with activated pyridines [69, 70]. The first examples of this chemistry involved either 77-alkyl-pyridinium salts in the presence of DDQ, or pyridine and terminal alkynes as activating agents in a one-step protocol. The reaction proceeds under mild conditions that include AI2O3 catalysis. Quinolines 1 and chloroformates afford the expected adducts 68. The latter structures can be easily oxidized with O3 to provide the substituted indoles 69 (Scheme 12a). Isoquinolinephosphonates obtained this way have been used in Wittig-Homer chemistry. The whole sequence offers ready access to alkyl substituted isoquinolines [71]. Analogously, sUyl substituents have been introduced into A-acylated pyridines by using silylcuprates [72]. 

Compounds whose structures include a quinone moiety have been intensively investigated as potential antitumor agents. At least two quinones, mitomycin C and diaziquone, that have found their way to the clinic. These compounds in addition include a reactive aziridine ring. A recent entry that incorporates both those features, apaziquone (135), also known as E09, may be viewed as an oxidized indole. In the key reaction of a succinct synthesis to this agent, quinone 129 is allowed to react with... 

Hamana, M., Kumadaki, I. Reaction of aromatic N-oxides with indoles in the presence of an acylating agent. Chem. Pharm. Bull. 1967, 15, 363-366. 

Copper has been demonstrated to mediate cyanation of aryl bromides and iodides through the activation of C-CN bonds (Scheme 20). Phenylacetonitrile [64], malononitrUe [65], and even acetonitrile as a reaction solvent [66] have been reported to serve as cyanating agents. 2-Phenylpyridines [67] and indoles [68] are directly cyanated by copper-mediated cyanation reaction using phenylacetonitrile, which is supposedly oxidized first at its benzylic position to give benzoyl cyanide, which further reacts with copper complexes to generate a cyanocopper species responsible for the cyanation event. Nevertheless, detailed mechanisms of these cyanation reactions remain elusive. 

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