Indole derivatives, oxidation

Indole derivatives, oxidation, biochemical multiple 17, 249 Indolenideniumethyl nitronates... 

Three new papers bearing on the structure of strychnine have become available too late for inclusion in this summary of recent work. Woodward, Brehm and Nelson have compared the ultra-violet absorption spectra of strychnine and Leuchs s strychnone (p.. 559) and used the results for a discussion of the relationship of the two alkaloids. Prelog and Kathriner have investigated the oxidation of strychnine, i/t-strychnine and brucine by permanganate in weakly acid solution and Bailey and Robinson from a study of the brucones have confirmed the conclusion of Woodward et al. that Leuchs s strychnone is a true indole derivative. Mention must also be made of a paper by Clemo and King on new reduction products of strychnine, of which a preliminary account has been published with a summary of the ensuing discussion. 

The alkaloid iboquine, a piperidinoquinoline, was derived in an analogous manner by air-oxidation of ibogaine, an indole derivative. 

When 1-methyl-, 1,2- and 1,3-dimethyl-indoles were oxidized on a platinum electrode in methanolic ammonium bromide solution, in addition to the oxidation products, products of nuclear bromination at the 3-and 5-positions were observed. 1,2- Dimethylindole (20) gave 3-bromo-1,2-dimethylindole (81CCC3278) [bromine in chloroform gave the same product (85CHE786)]. In acidic conditions the amidinium cation formed from 20 was brominated in the 5-position (Scheme 14). Acylated 2-aminoindoles reacted similarly in neutral media to give 3-bromo derivatives and when protonated to give 5-bromo products. Bromine in chloroform transformed l-methyl-2-dimethylaminoindole (21) into the 3-bromo derivative (85CHE782) (Scheme 15). 

Vinyl- and acetylenic tricarbonyl compounds are reactive dienophilic components in Diels-Alder reactions. Cycloadditions of these compounds with substituted butadienes were recently used to develop a new synthetic approach to indole derivatives [14] (Scheme 2.9) by a three-step procedure including (i) condensation with primary amines, (ii) dehydration and (iii) DDQ oxidation. 

The unexpected formation of cyclopenta[b]indole 3-339 and cyclohepta[b]indole derivatives has been observed by Bennasar and coworkers when a mixture of 2-in-dolylselenoester 3-333 and different alkene acceptors (e. g., 3-335) was subjected to nonreductive radical conditions (hexabutylditin, benzene, irradiation or TTMSS, AIBN) [132]. The process can be explained by considering the initial formation of acyl radical 3-334, which carries out an intermolecular radical addition onto the alkene 3-335, generating intermediate 3-336 (Scheme 3.81). Subsequent 5-erafo-trig cyclization leads to the formation of indoline radical 3-337, which finally is oxidized via an unknown mechanism (the involvement of AIBN with 3-338 as intermediate is proposed) to give the indole derivative 3-339. 

A number of other indole derivatives have also been observed to yield CL subsequent to oxidation. Among these is skatole (3-methylindole), which emits light after oxidation by 02 under strongly alkaline conditions [9],... 

An intramolecular Diels-Alder reaction of allenic dienamide 181 provided the tet-rahydroindole ring system 182, which was oxidized with DDQ or Mn02 to give indole derivatives [147]. 

Psilocybin (Figure 3.5a) and psilocin (Figure 3.5b) are indole derivatives substituted in position 4 by a hydroxyl group, where psilocybin is phosphory-lated. Due to its ionic properties, psilocybin is soluble in water. In addition, phosphorylation protects psilocybin from oxidative degradation. Both compounds are found to affect laboratory animals, but there is evidence that only the dephosphorylated form, psilocin, is the active species. In their structure the toxins resemble serotonine, a biogenic amine known to be a neurotransmitter. 

Reduced indole derivatives can be synthesized by using the phenolic oxidation approach. Thus, A-alkyl-A-benzoyltyramines 120, on treatment with IBTA in trifluoroethanol (TFE), followed by aqueous workup, afford the hexahydroindol-6-ones 122. The formation of 122 is rationalized by intramolecular Michael-type addition of amino group to the double bond of the intermediate dienone 121 (91JOC435) (Scheme 33). 

Another important example of oxidative cyclization leading to bridgehead heterocyclic compound is the conversion of indole derivative 211... 

The resulting heterocycles can be structurally manipulated, e.g., reduced or desilylated either during complexation or after demetallation. Another possibility consists in using the primary products, obtained by the cobalt-mediated cycloaddition, as synthetic intermediates for further catalytic transformations. Indole derivatives have been cocyclized at cpCo to give 4a,9a-dihydro-9 f-carbazoles or, after oxidation, precursors for strychnine (63T247 86JA2091 87MI7) [Eq.(36)]. 

The influence of a C-2 substituent upon the reaction course has been investigated. If only a 2-aryl group is present, as in 145 (R = H), then 4-quinolones 146 are formed (85H2375). But ferricyanide oxidation of 2,4-diphenyl derivatives resulted in the release of the 2-phenyl group and formation of the quinolones 147 instead of the exptected indole derivatives (83CCC2965). 

Triple bonds are in general more reactive than double bonds as is exemplified in the following process (1.2.).13 The active catalyst is HPdOAc, which is formed by the oxidative addition of acetic acid onto Pd(0). The organic substrate is attached to the palladium in a regio- and stereospecific step that is followed by an oxidative addition (N.B. Pd(II)-Pd(IV) transition) and reductive elimination, or alternatively carbopalladation and reductive elimination, to give the indole derivative. 

In an analogous process o-allylanilines were converted into indole derivatives by Hegedus (3.66.). Since the process is initiated by a palladium(II) catalyst and produces palladium(O) as product, recycling of the catalyst had to be ensured by the addition of stoichiometric amounts of an oxidant (e g. benzoquinone).83... 

The ability of palladium(II) acetate to mediate the oxidative ring closure of indole derivatives containing a pendant aromatic ring has been exploited... 

V-aryl-o-haloanilines can be converted into indole derivatives in a palladium catalysed oxidative addition, C-H activation sequence. The transformation has been utilized extensively in the preparation of polycyclic compounds. In a recent example, leading to the formation of the carbazole ring system, Larock and co-workers demonstrated that the formation of the... 

The electrochemical oxidation of aromatic aldehydes (1) must be studied in strongly alkaline media. Acidity functions for strongly alkaline aqueous solutions of alkali metal and quaternary ammonium hydroxides, corresponding to dissociation of proton (H ), are well established (2, 3). Substituted anilines and diphenylamines (4,5) and indoles (6) were used as acid-base indicators for establishment of such scales, but whether an acidity scale based on one type of indicator can be rigorously applied to acid-base equilibria involving structurally different acidic groups for reactions in strongly alkaline media remains questionable. For substituted anilines, behavior both parallel (7) and nonparallel (8) to the H scale based on indole derivatives has been reported. The limited solubility of anilines in aqueous solutions of alkali metal hydroxides, the reactions of the aniline derivative with more than one hydroxide ion, irreversible substitution reactions (9), and the possibility of hydroxide ion addition rather than... 

Isatogens may be prepared by two general methods involving either an intramolecular cyclization or oxidation of a 2-substituted indole derivative. 

An intermediate oxazepine (195) has also been postulated to account for the ring contraction of 2,3-trimethylenequinoline 1-oxide (196) to 4-oxo-l,2,3,4-tetrahydrocarbazole (197) on irradiation.167 The intermediate oxazepine has been isolated in the analogous conversion of 1,2,3,4-tetrahydroacridine 10-oxide,167 but acridine 10-oxide (198) itself yields only the indole derivative (199).168... 

Some organic reactions produce ultraweak chemiluminescence. Grignard reagents [75, 76] and indole derivatives [13], for example, have very low < )cl (10 5— 10 8) when they are oxidized. Many cellular systems also produce this dim or low-level chemiluminescence during phagocytosis [77], chemotaxis, and mitosis... 

Treatment of the product derived from reaction of the iV-oxide 1 with trifluoroacetic anhydride with sodium borohydride gives the tetracyclic indole derivative 2. 

One of the starting materials, the bromoindolinemesylate 183 was obtained from the commercially available 5-hydroxyindole by mesylation followed by successive treatment of the resulting indole derivative with sodium cyanoborohydride and bromine. Coupling of 183 with the known boronic acid 184 in the presence of zero valent palladium complex led directly to the lactam 185, the intermediate carbinolamine 186 formed initially in the reaction suffering facile aerial oxidation during work-up. On reduction with sodium (2-methoxyethoxy)aluminium-hydride, the amide 185 yielded the aminophenol 187 which on chromatography underwent oxidative aromatisation to 182 in 54% yield. 

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