Indole-3-acetic acid chemistry

Most of the early applications of palladium to indole chemistry involved oxidative coupling or cyclization using stoichiometric Pd(II). Akermark first reported the efficient oxidative coupling of diphenyl amines to carbazoles 37 with Pd(OAc)2 in refluxing acetic acid [45]. The reaction is applicable to several ring-substituted carbazoles (Br, Cl, OMe, Me, NO2), and 20 years later Akermark and colleagues made this reaction catalytic in the conversion of arylaminoquinones 38 to carbazole-l,4-quinones 39 [46]. This oxidative cyclization is particularly useful for the synthesis of benzocarbazole-6,11-quinones (e.g., 40). 

The next three procedures provide useful synthetic intermediates. A stereospecific synthesis of ETHYL (Z)-3-BROMO-2-PROPENOATE affords an alternative vinyl bromide partner for the coupling chemistry in the preceding procedure. A very simple but elegant illustration of the flash vacuum pyrolysis technique is used to prepare BENZOCYCLOBUTENONE from o-toluoyl chloride. Another member of the functionalized indole family of synthetic intermediates is presented in a four-step procedure for 5-METHOXYINDOLE-2-ACETIC ACID METHYL ESTER. 

Martel, R. R., Demerson, C.A., Humber, L.G., Philipp, A.H., Etodolic acid and related compounds. Chemistry and antiinflammatory actions of some potent di- and trisubstituted 1, 3, 4, 9-tetrahydropyrano[3, 4-b]indole-1-acetic acids, J. Med. Chem. 1976, 19, 391-395. 

Chemistry and Physiology of Conjugates of Indole-3-Acetic Acid... 

We have studied the reaction of similar cyclic -substituted enaminones which yielded indolones when the reaction was carried out in acetic acid and the quinones had lower oxidation potential, thus preventing prior oxidation of the enaminones. Secondary aminomethylene derivatives of cyclopentanone, cyclohexanone and cycloheptanone reacted with the quinones to presumably form intermediate spiro compounds, as a consequence of normal enaminone chemistry. However, this was unexpectedly followed by rearrangement with ring expansion to indolones (equation 158). In this way carba-zoles, cycloheptindoles and cyclooctindoles can be obtained by a simple entry to this class of indoles, although partially in low yields222-224. Due to their bifunction-ality the produced indol-2-ones are versatile synthons for fused heterocycles (e.g. triazepino- and pyrazino-carbazoles) which become easily accessible225,226. 

Muller, A. and WeUer, E.W. 2000. lAA-synthase, an enzyme complex from Arabidopsis thali-ana catalyzing the formation of indole-3-acetic acid from (5)-tryptophan. Biological Chemistry, 381 679-86. 

Several new routes involve formation of one carbon-carbon bond in pre-formed substrates. Palladium-catalyzed cyclization of /3-hydroxyenamine derivatives has been employed in a route to substituted pyrroles and 4,5,6,7-tetrahy-droindoles with multiple substituents by formation of the C-3-C-4 bond as the key feature, as illustrated by construction of the molecule 534 (Equation 146) <2006T8533>. Zinc perchlorate-catalyzed addition of alcohols to the nitrile functionality of a-cyanomethyl-/3-ketoesters, followed by annulation gave access to a series of substituted ethyl 5-alkoxypyrrole-3-carboxylates <2007T461>. Similar chemistry has also been used for synthesis of a related set of pyrrole-3-phosphonates <2007T4156>. A study on preparation of 3,5,7-functionalized indoles by Heck cyclization of suitable A-allyl substituted 2-haloanilines has also appeared <2006S3467>. In addition, indole-3-acetic acid derivatives have been prepared by base induced annulation of 2-aminocinnamic acid esters (available for instance from 2-iodoani-lines) <2006OL4473>. 

The first example of an indole-2,3-quinodimethane (IQM) undergoing a Diels-Alder cycloaddition to furnish a carbazole was reported by Plieninger and coworkers in 1964 [9], Thus, indole-3-acetic acid was readily converted to pyrano[3,4-fe]indol-3-ones upon treatment with carboxylic acid anhydrides (Scheme 1, equation 1). These stable synthetic equivalents of IQMs undergo Diels-Alder reactions with electron-deficient dienophiles (A-phenytma-leimide,maleicanhydride,dimethylacetylenedicarboxylate) (equation 2). Plieninger s discovery notwithstanding, it was Moody and coworkers who parlayed this chemistry into a powerful carbazole synthesis (equations 3,4) [10-18],... 

Q2lid ii9D-.9f Q90)8i N iyil ] l Ei i while it it is certainly true that much of the early electrochemistry of natural materials was carried out on simple materials such as alcohol or acetic acid, more complex substrates would be more likely to produce unpredicted chemistry. Our first interest in this type of work was aroused by the paper of Allen and Powell (58) in which the behavior of a number of complex indole alkaloids was examined voltammetrically. Although products were not isolated, such complex molecules should produce some new and unique chemistry. Unfortunately, the work has never been followed up. We did confirm... 

Atkin RK, Barton GE, Robinson DK (1973) Effect of root-growing temperature on substances in xylem exudate of Zea mays. J Exp Bot 24 475-487 Atsmon D, Lang A, Light EN (1968) Contents and recovery of gibberellins in monoecious and gynoecious cucumber plants. Plant Physiol 43 806-810 Backus GE, Schrank AR (1952) Electrical and curvature responses of the Avena coleoptile to unilateral illumination. Plant Physiol 27 251-262 Bandurski RS (1978) Chemistry and physiology of myo-inositol esters of indole-3-acetic acid. In Wells W, Eisenberg F (eds) Cyclitols and phosphoinositides. Academic Press, London New York, pp 35-54... 

Total synthesis of these toxins presented peptide chemistry with several problems, in particular formation of the sulfur bridge. The latter was explored with model compounds 430, 431). It was found 428) that the coupling reaction between the sulfur of N-acetyl-L-cysteine and the 2-position of the indole nucleus of N-acyl-L-trypto-phan was reproducible and profitable if glacial acetic acid was used as a solvent. The formation of the intermediate S-chloride from the cysteine derivative and N-chlorosuccinimide at room temperature was followed colorimetrically, and the tryptophan component added at the moment of maximum extinction. 

Published methods for decarboxylation of indole-2-carboxylic acid to form indole include pyrolysis or heating with copper-bronze powder, cop-per(I) chloride, copper chromite, copper acetate or copper(II) oxide, in for example, heat-transfer oils, glycerol, quinoline or 2-benzylpyridine. Decomposition of the product during lengthy thermolysis or purification affects the yields. From the perspective of green and sustainable chemistry, these methods have disadvantages associated with the choice of media and reagents as well as with the yields. Quite remarkably, however, in water at 255 °C, decarboxylation was quantitative within 20 min (Scheme 20) [77]. 

The Pictet-Spengler reaction has been combined with Ugi multi-component chemistry to construct a number of polycyclic indoles. Isonitrile derivatives prepared from tryptamine (or methyl tryptophanate), a carboxylic acid and formaldehyde condense with aminoacetaldehyde diethyl acetal. A few examples employed substituted aldehydes [352]. 

Dimethylformamide dimethyl acetal has been used as a methine group source for various heteroring closures, particularly for an efficient 2-step indole synthesis from nitro compounds . The investigation of 3H-1,4-benzodiazepines with their two imino functions, particularly one with an a-iminonitrile function, has been added to the highly versatile chemistry of these heterocyclics Barbituric acid and 2,3,5-trioxopyrrolidine derivatives have been obtained through easy base-catalyzed reactions of active methylene compounds with isocyanates From the neighboring biochemical area come these contributions in preparative enzyme chemistry a-Chymotrypsin as well as citrus... 

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