Indolines oxindoles

Additionally, the intramolecular cyclization of 2-halo-AT-allylanilines provides optional proeedures for indole derivative synthesis. Many transition metal eatalysts have been developed in this field, such as cobalt, nickel and palladium, but stoichiometric amounts of catalysts are needed. In 1987, a eatalytie version was developed by Laroek and Babu. In the pres-enee of a eatal54ie amount of Pd(OAe)2, indoles, indolines, oxindoles, qui-nolones, isoquinolines and isoquinolones were formed in high yields in short reaetion times under mild temperatures (Seheme 2.106). 

The application of Heck cyclizations to the synthesis of indoles, indolines, and oxindoles was discovered independently by Mori-Ban s [296-298], and Heck s groups [299]. These investigators found that Pd can effect the cyclization of o-halo-lV-allylanilines to indoles under Heck conditions [300], The cyclization of o-halo-/V-allylanilines to indojes is a general and efficient methodology, especially with the Larock improvements where he cyclized o-halo-W-allylanilines and o-halo-N-acryloylanilides into indoles and oxindoles [301]. For example, the conversion of 279 to 280 can be performed at lower temperature, shorter reaction time, and with less catalyst to give 3-methylindole (280) in 97% yield. Larock s improved conditions, which have been widely adopted, are catalytic (2%) Pd(OAc)2, n-Bu4NCl, DMF, base (usually... 

The C-2 and C-3 hydroxy derivatives of pyrrole are special in the sense that the tautomeric equilibria favor the pyrrolinone structures (see Section 3.04.6.2). Furthermore, the general synthetic methods are not usually applicable so that we will call attention in this section not only to the methods of directly introducing these substituents, which are rare, but also to those ring construction processes which specifically give the pyrrolinones and indolinones. The indole derivatives have widely used trivial names, oxindole (5) for indolin-2-one and indoxyl (6) for indolin-3-one, Carbocyclic hydroxy substituents in indole and carbazole, on the other hand, for the most part act as normal aromatic phenolic groups. These compounds are usually prepared by application of the standard ring syntheses. 

Many early claims of having prepared simple 1-hydroxyindoles have proved to be unfounded, although the unusually stable l-hydroxy-2-phenylindole was obtained in 1895.1-Hydroxyindole itself polymerizes on attempted isolation, while O-acylation, O-alkylation, or the presence of substituents greatly stabilizes the molecule. One 1-hydroxyindole antibiotic has been identified and is the only 1-hydroxyindole derivative isolated from natural sources so far. In contrast, a substantial number of 1-methoxyindoles occurs in various plants, and some of these may inhibit tumor formation in mammals. The biochemistry of these compounds, which include 1-methoxy-indoles, -indolines and -2-oxindoles, has not been widely investigated and could be a very fruitful area for new research which might well lead to novel medicinal agents and other useful compounds. 

In a model of gardmultine [544] the 18 -methyl is seen to lie over the indoline moiety thus providing an explanation of its low frequency absorption (<5 0-88). Treatment of [544] with hydrochloric acid gives the conformationally more mobile oxindole [545] which now shows absorption for the 18 -methyl protons at d 1-43. (324)... 

The indolines 95 or oxindoles 96 have been reported as products originating from the base-or fluoride-mediated exo-trig cyclization of the intermediates 97, derived from the precursors 98 by treatment with phenyliodine(III) diacetate (PIDA) <02JOC3425>. 

Photochemically mediated cyclizations. These have been used to produce oxindoles <1980JA3646>, indolines 73 (Scheme 46) <1980T1757>, and 2,3-dihydrobenzofurans 74 (Scheme 47) <1978JA2150>. 

Quite early in the chemical studies of Wieland and King, evidence accumulated that the calabash curare alkaloids are indole derivatives, and with present knowledge it is possible to correlate the UV-spectra of many of them with one or another of the following related chromo-phores formally derived from the indole nucleus by oxidation, reduction, and substitution, or combinations of these processes. They are the indoline (II), 2-hydroxyindoline and the derived ethers (III), iV-hydroxy-alkylindoline and its ethers (IV), 2-methyleneindoline or 1-vinylindoline (Va or Vb, respectively), indole (VI), oxindole or 1-acylindoline (Vila or Vllb, respectively), -indoxyl (VIII), and /J-carbolinium (IX) systems it is not possible to distinguish with certainty by spectroscopic methods between the chromophores III and IV, between Va and Vb, or between Vila and Vllb. 

The substrate 64 has been converted to the acetate 65 using phenyliodine(lll) diacetate (PIDA), followed by annulation to the indoline 66 (Scheme 9). A similar methodology can also be applied for preparation of oxindoles <2002JOC3425>. 

J-Oisubstitated SH-indoks. 3,3-Disubstituted 311-indoles (3) can be prepared readily by lithium aluminum hydride [or sodium bis-(2-mcthoxyethoxy)aluminum hydride, 3, 260-261 this volume] reduction of 3,3-disubstituted oxindoles (1), followed by oxidation of the indoline (2) with activated manganese dioxide or potassium permanganate in acetone. 

The reduction of the indolinones 209 with NBH in methanol leads readily to the indoles 210 in 56-96% yield. Intermediacy of the corresponding alcohols has been proposed." The reduction of indoles and related compounds has been the subject of a previous review." Oxindoles (211) are reduced with LAH to indoles (212) but in low yields. Small amounts of the indolines 213 are also obtained. Dimerization on hydride reduction has also been recorded." ... 

The photochemically induced cyclisation of diphenylamines to carbazoles is well established in the chemical literature. Details of the first example of such a cyclisation in W,W-diarylsulphon-amides have been published, and a similar conversion of the N-phenylenamine (35) into the indoline (36) has been used in a new synthesis of oxindoles. Analogous cyclisations accompanied by the elimination of HX have also been reported the pyridinium bromide (37), for example, is converted in this way into the pyridoisoindolium bromide (38). °... 

Under indole alkaloids we include naturally occurring bases or their derivatives which contain a true indole nucleus or a modification thereof, indoline (dihydroindole), N-acyl-indoline, indolenine, oxindole etc. 

The products of the xanthate transfer reactions being themselves xanthates, a second radical step may be envisaged. This possibility may be exploited for the synthesis of several important aromatic derivatives such as oxindoles, indolines, tetralones, dihydroisoquinolinones, etc. [37]. The two examples in Scheme 21 give an idea of... 

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