Indol oxidative dimerization

Jap-KIingermarm reactions, 4, 301 oxidation, 4, 299 reactions, 4, 299 synthesis, 4, 362 tautomerism, 4, 38, 200 Indole, 5-amino-synthesis, 4, 341 Indole, C-amino-oxidation, 4, 299 tautomerism, 4, 298 Indole, 3-(2-aminobutyl)-as antidepressant, 4, 371 Indole, (2-aminoethyl)-synthesis, 4, 278 Indole, 3-(2-aminoethyl)-synthesis, 4, 337 Indole, aminomethyl-reactions, 4, 71 Indole, 4-aminomethyl-synthesis, 4, 150 Indole, (aminovinyl)-synthesis, 4, 286 Indole, 1-aroyl-oxidation, 4, 57 oxidative dimerization catalysis by Pd(II) salts, 4, 252 Indole, 1-aroyloxy-rearrangement, 4, 244 Indole, 2-aryl-nitration, 4, 211 nitrosation, 4, 210 synthesis, 4, 324 Indole, 3-(arylazo)-rearrangement, 4, 301 Indole, 3-(arylthio)-synthesis, 4, 368 Indole, 3-azophenyl-nitration, 4, 49 Indole, 1-benzenesulfonyl-by lithiation, 4, 238 Indole, 1-benzoyl photosensitized reactions with methyl acrylate, 4, 268 Indole, 3-benzoyl-l,2-dimethyl-reactions... 

Oxidative dimerization of indoles has also been reported to be catalyzed by Tl(III) salts <78IJC(B)422), whilst Co(II) salts cause oxidative cleavage of indoles (79MI30503). 

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. 

The viability of the azacyclopentanadienone ion 73,63 as proposed in our mechanism, fits in with other literature precedents. Recently, based on mechanistic evidence, the oxidative dimerization of indoles to bisin-dol-3-ones has been suggested to proceed via a-ketoiminium ion analogous to 73.64 The neutral relative to such a species, 3//-indol-3-one (75), has been suggested as a possible intermediate in the base-catalyzed... 

Hoshino et al. described that in cultures of Chromobacterium violaceum, lycogalic acid (35, = chromopyrrolic acid) was derived from tryptophan [18]. It was therefore assumed that lycogalic acid (35) was formed by oxidative dimerization of 3-(indol-3-yl)pyruvic acid followed by reaction of the resulting 1,4-dicarbonyl intermediate with an equivalent of ammonia. On the basis of this idea, lycogarubin C (33) was synthesized from methyl 3-(indol-3-yl)pyruvate (37) in a simple one-pot process (Scheme 4). 

There are examples when photochemically generated radicals undergo an oxidative dimerization similar to some examples shown in Section 2.02.1.5. In the case of hapalindole E (223), irradiation leads to the dimer (224), presumably by a mechanism which involves photoinduced interaction between the indole ring and the isonitrile group to give an indolyl radical (Equation (68)) <89J0C719>. 

Aryl and alkyl-substituted diynes and tetraynes have been synthesized in good yields (82-99%) by TBAF-promoted desily-lation and Cu-catalyzed oxidative dimerization of triisopropylsi-lyl (TlPS)-protected acetylenes (eq 38). Copper acetate was used as oxidant in this reaction. Aryl- and alkenyl alkynes were made under similar conditions (eq 39). Pd/C with TBAF was used in ligand- and copper-free, one-pot, domino Halex-Sono-gashira reactions. Similarly, TBAF promoted the synthesis of 2-substituted indoles by a tandem Sonogashira/cyclization reaction of 2-iodoanilines and terminal alkynes. ... 

Since its discovery, the Songashira reaction has been a valuable tool for the functionalization of aromatic and heteroaromatic halides with the versatile alkyne function [9]. Among the many possible alkyne transformations, these derivatives can undergo cyclization reactions to prepare indoles, benzo- and heteroaryl- furans, and other useful pharmacophores. One of the difficulties of the reaction is the propensity of acetylenes to oxidatively dimerize under the reaction conditions, particularly when the cross-coupling reaction is slow as in the case of aromatic... 

An enzyme-substrate complex has been detected in the oxidative dimerization of L-(-)-tyrosine by HRP(i) to give HRP(ii). The pH dependence of the reaction reveals an enzyme protonation at pATa 5.42 with a less reactive protonated form. The hydroperoxide of indole-3-acetic acid (lAA) is important in the autoxidation of lAA catalysed by HRP. Formation of HRP(i) by reaction with the hydroperoxide is easier for the neutral isoenzyme than for the acidic species at pH 4.4 and this determines the catalytic activity. HRP(ii) is detected as an intermediate in the reaction and it reacts with lAA to form radicals. The involvement of both HRP(i) and HRP(ii) is proposed in the autoxidation of 2-nitro-propane to acetone and HNO2, catalysed by HRP. 

Numerous biocatalytic arene dimerizations mediated by laccases are also described. 3-Hydroxyanthranilic acid 148 is a natural substrate for oxidative dimerization by fungal laccases to give cinnabarinic acid 149, and the applicability of this transformation to other nonnatural substrates has been demonstrated (e.g., 150 to 151) [79, 80]. Crossed dimers arising from the oxidative coupling of two different hydroxyaniline substrates have also been reported [81]. Some more unusual examples of laccase-mediated oligomerizations include the oxidative dimerization/ cyclization of tyrosol 152 to give 153 [82] and the oxidative trimerization of indole 154 to give... 

Future efforts in the CDC of arenes will perhaps include enzyme-mediated reactions, since enzymes have low toxicity, high catalytic turnovers, and are able to run in very mild conditions. In 2006, °° dTschia and co-workers used peroxidase enzymes to catalyze the oxidative dimerization of indole derivatives. This technology, albeit low yielding, appears to be an excellent lead to optimize cross-dehydrogenative-coupling. 

The formation of diastereomers of 4-[4 -(6-hydroxyquinolyl)]-5-hydroxytryptophan (27) upon oxidation of 5-HTPP is a rather unusual reaction. It seems unlikely that these diastereomers would be formed from different intermediates than are the 4,4 -dimers (14) or tryptophan-4,5-dione (17). The structures of the indole-quinoline dimers suggest that the C(4)-position of one 5-HTPP residue must attack the C(3)-position of another residue. There are several ways that a coupling of 5-HTPP residues would occur. It was originally proposed that quinone imine 15 is... 

Alkylation reactions by the iminium methide species are well known in the mitomycin and mitosene literature 4,49,51-53 and are largely responsible for the cytotoxicity/antitumor activity of these compounds. As illustrated in Scheme 7.8, the electron-rich hydroquinone intermediate can also be attacked by the iminium ion resulting in either head-to-head or head-to-tail coupling. The head-to-head coupling illustrated in Scheme 7.8 is followed by a loss of formaldehyde to afford the coupled hydroquinone species that oxidizes to the head-to-head dimer upon aerobic workup. Analogous dimerization processes have been documented in the indole literature, 54-56 while the head-to-tail mechanism is unreported. In order to... 

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