Indolyl radical

In one of the earliest reports on indole radicals, Sundberg (90JOC6028) outlined an intramolecular radical addition of a 3-indolyl radical onto an isolated double bond (for the synthesis of analogues of Iboga alkaloids) to yield 128a-c providing a rare example of an S-endo-trig cyclisation (Scheme 31). 

Srinivasan (96TL2659) synthesised a series of 4-substituted jS-carboline derivatives using the radical addition of 3-indolyl radicals to an isolated double bond, in a 6-exo-trig fashion to give tricyclic 130a-c and 132 (Scheme 32). 

A radical ipso substitution at the 3-position of 2,3-disubstituted indoles has also been reported in their reaction with benzoyl-r-butyl nitroxide leading to (227) or, with the 2-substituted indole, the dimer (228) (cf. Section 3.05.1.4) (81CC694). In contrast with the benzoyloxylation reactions the nitroxide radical initially abstracts the hydrogen atom at the 1-position to form the indolyl radical. This mechanism is supported by the failure of the corresponding 1 -methylindole to undergo an analogous oxidation. 

Candeias LP (1998) Indolyl radicals. In Alfassi ZB (ed) A/-Centered radicals. Wiley, New York, pp 577-597... 

DeEilippis, M. R., Murthy, C. P., Broitman, E., Weimaub, D., Earaggi, M., and Klapper, M. H., 1991, Electrochemical Properties of Tyrosine Phenoxy and Tryptophan Indolyl Radicals in Peptides and Amino Acid Analogues, J. Phys. Chem. 95 341693419. 

It is necessary that an antioxidant protects cells at all stages of oxidative stress, and therefore an antioxidant should be able to scavenge the secondary radicals produced by the reaction of primary radicals with biomolecules. Radiation chemists designed methods to study reactions of secondary radicals from amino acids of proteins and base and sugar radicals of DNA with antioxidants.The most commonly employed aromatic amino acid radicals generated by radiation chemical experiments are the indolyl radicals of tryptophan (TRP ), the... 

It has recently been shown that Calycanthus floridus plants, on being fed with [2- C]tryptophan, produce specifically labelled folicanthine (6). - Tryptophan is thus serving as a specifically monomeric precursor of folicanthine. It seems highly probable that the biosynthesis also includes the coupling of two indolyl radicals of the type (16). 

Indolyl radicals can be generated under standard conditions by reacting 2-bromoindole with tributyltin hydride. 3-Methyl-1-tosylindole can be cyanated at C-2 in good yield by a mixture of TMSCN and PIFA via oxidation of the indole to a cation radical, then addition of cyanide anion. ... 

The intramolecular one-electron redox reaction (equation 1) involves electron transfer from the phenol group of the tyrosine side chain to the indolyl radical of the tryptophan side chain (Trp ). 

Photocyclization of iV-chloroacetyl amines has been used previously in the synthesis of nitrogen heterocycles, and the reaction of the substituted amine (166) leads to a benzazepinone that can be elaborated to give pseudoprotopine alkaloids. Y-Chloroacetyl derivatives of the seven isomeric indolylethylamines give azepinoindoles and azocinoindoles by photocyclization. Quantum yields for the reaction are correlated with calculated (CNDO/2 and INDO) electron densities, and on this basis mechanisms are suggested the conclusion is that both indole radical cations and indolyl radicals (for the 1-substituted compounds) are... 

Correlation of the chemical properties of the indolyl radicals from derivatives of indole-3-acetic acid failed to demonstrate clear structure/activity relationships for the peroxidase-catalysed cytotoxicity [159], and further work is required [160]. 

Indolyl radicals can be generated under standard conditions by reacting 2-bromoindole with tributyl tin hydride. 

Indolyl radicals, as pyridyl radicals, are amongst the most widely explored heteroaromatic radicals. They have frequently been used as intermediates for the synthesis of a number of natural compounds and the Jones group have published extensively in this area as outlined below. 

From the same group, the first example of intermolecular radical additions of indolyl radicals to double bonds has been reported (99CC1761) (Scheme 26). 

Reaction of indole 109 with a number of alkenes llOa-d is described (99CC1761). The expedient use of a catalytic amount of BusSnCl in the presence of reducing agent NaCNBHs, ensured that the lowest concentration of BuaSnH was obtained (86JA303). Further examples are available in the original report, outlining the reactivity of the 2-indolyl radical towards a number of alkenes. Noteworthy in their approach, is... 

Following their investigation on the reactivity of 2-indolyl radicals, Jones (00TL4209) reported on their intramolecular addition reactions to benzene rings tethered to the nitrogen of the indole with various length chains (Scheme 28). 

An additional example of 1,5-H atom abstraction by a 2-indolyl radical has been described by Gribble (01CC805) (Scheme 29). 

The indole-containing alkaloid rutaecarpine 126 has been synthesised via cyclisation of a 2-indolyl radical onto the 2-position of a 4-quinazolinone (070BC103). The radical precursor 124 was prepared by N-alkylation of the 3-position of the 4-quinazolinone followed by bromination of the 2-position of the indole ring. Slow addition of BusSnH gave 15% of rutaecarpine 126 and 57% of the reduced product 125. 

In early studies on the 4-indolyl radical, Boger (88JA1321) synthesised the antitumour-antibiotic CC-1065, using an intramolecular radical addition to an alkyne in a 5-exo-dig cyclisation (Scheme 36). 

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