The Oxindole Group

The oxindole structure (XXIX) of this alkaloid was established by consideration of a combination of spectral evidence. Thus, its mass spectrum confirmed the analytically found molecular formula of C23H30N2O6 bj showing a molecular ion at m/e 430. Further, it exhibited a strong peak at m/e 225 due to the fragment e, two mass units higher than the corresponding ion in the mass spectra of mitraphylline and carapanau-bine which have a C-16, C-17 double bond. Other peaks in the spectrum are also shifted by the appropriate number of mass units expected for 

This amorphous base (C23H28N2O6) was isolated in small amounts from the aerial parts of Vinca major. Its mass spectrum was superimpos-able upon that of carapanaubine and the UV-, IR-, and NMR-data agreed well with a structure of the type XXXIIa-c. The NMR-spectrum of the alkaloid further indicated a pair of o-hydrogen atoms in the aromatic ring. However, a decision could not be made among the three possible structures (31). 

This alkaloid (C23H28N2O6) is isomeric with carapanaubine, as evidenced by NMR- and mass-spectral data. Treatment with hot acetic anhydride causes its conversion to isomajdine (mp 200°-206° [a]Jf —90°). The structure XXXIV has been proposed for this new base (30). 

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In the oxindole group, formosanine and mitraphylline have been isolated from the bark of Uncaria elliptica R.B. ex G. Dm.,61a and rumberine (10-hydr-oxyisopteropodine) and palmirine (10-methoxyisopteropodine) from the aerial parts of Hamelia patens Jacq.616 Rauvoxinine has been reported14" to be present in the leaves of R. psychotrioides, but the identification rests mainly on its mass spectrum. 

The constitution (I) for gelsemine is clearly incapable of explaining all these experimental data, but those which were subsequently proposed were also inadequate in one or more respects. On the basis of the bromina-tion experiments, and the probable proximity of the double bond to the oxindole group, the alternatives Va and Vb were advanced (66, 71). In both formulas, the position of the ether link was not specified, although... 

An unusual case of addition of a carbanion to an unconjugated carbon-carbon double bond is shown in Scheme 47a. The subsequent transfer of the amide group is also noteworthy (80CC1042). The intramolecular addition of a carbanion to an aryne is a more widely established process. Such reactions have been applied to the synthesis of indoles (Scheme 47b) (75CC745> and oxindoles (Scheme 47c) (63JOC1,80JA3646). 

Although the yields of 38 were high, the oxindole (39) was also formed as a by-product. This exemplifies the problem of reducing the nitro group specifically to a hydro xylamine. 

The same group recently disclosed a related free radical process, namely an efficient one-pot sequence comprising a homolytic aromatic substitution followed by an ionic Homer-Wadsworth-Emmons olefination, for the production of a small library of a,/3-unsaturated oxindoles (Scheme 6.164) [311]. Suitable TEMPO-derived alkoxy-amine precursors were exposed to microwave irradiation in N,N-dimethylformam-ide for 2 min to generate an oxindole intermediate via a radical reaction pathway (intramolecular homolytic aromatic substitution). After the addition of potassium tert-butoxide base (1.2 equivalents) and a suitable aromatic aldehyde (10-20 equivalents), the mixture was further exposed to microwave irradiation at 180 °C for 6 min to provide the a,jS-unsaturated oxindoles in moderate to high overall yields. A number of related oxindoles were also prepared via the same one-pot radical/ionic pathway (Scheme 6.164). 

A related cyclization of 2-(alkynyl)phenylisocyanates with terminal alkynes to oxindoles was also reported by the same group (Equation (115)).472 (E)-exo-olefinic oxoindoles are selectively obtained. It was proposed that a palladium acetylide generated by the C-H activation of terminal alkynes regioselectively inserts to the alkyne moiety and the resulting vinylpalladium intermediate adds to the C=0 part of the isocyanate to give a (Z)-oxindole. This (Z)-isomer is isomerized to the ( )-isomer under the reaction conditions through catalysis of the phosphine. 

This method was also effective for the preparation of ferf-butyloxycarbonyl (Boc)-protected bis-indolyloxindole from the corresponding Boc-protected 2-methylindole without cleavage of the Boc group. Furthermore, pyrrole and /V-me thy I pyrrole also react efficiently with isatin, under similar conditions, to afford 3,3-di(2-pyrrolyl) oxindole derivatives (Fig. 13). 

The probable pathway of the reaction is shown in Fig. 14 and it seems to be an addition of the indole to the carbonyl group of isatin, followed by the condensation of a second indole moiety on the same carbon, resulting in the formation of 3,3-di (3-indolyl)oxindole. 

The first microwave-assisted Wolff-Kishner reduction was described by Parquet and Lin in 199763. The transformation of isatin to oxindole was performed on a small scale in a domestic microwave oven in two steps with a total reaction time of 40 s, as compared to 3—4 h if classical heating was utilised (Scheme 4.36). The first step involved the transformation of the carbonyl group into the hydrazone with 55% hydrazine in ethylene glycol and medium power microwave irradiation for 30 s. In the subsequent reduction step, KOH in ethylene glycol was used to substitute the more hazardous sodium ethoxide. The reaction mixture was irradiated for 10 s and the product was obtained in a yield of 32%. 

The 3-methylene group of l-methoxy-2-oxindole (163) is easily ionized to give a carbanion that undergoes well-known types of reactions with alkyl halides or activated olefins without loss of the methoxyl group (e.g. 

The presence of the methoxyl group in gelseverine [410] largely affects the 13C shifts of the oxindole moiety and of the ra-orientated ethylidene side chain compared with shifts in gelsemine [411]. (249)... 

If the substituent at position 3 in the oxindoles 174 or benzoxindole 175 is a CHCOPh group, 2-phenyl-substituted 4-quinolinecarboxylic acids 176 [149] or 4-benzoquinolinecarboxylic acids 177 [150] respectively are formed when they are heated with concentrated hydrochloric acid in alcohol. Compound 174 (R = H) is not transformed into the corresponding acid 176 under the conditions of the Pfitzinger reaction [149],... 

The electrochemical and chemical stability of diamond makes it an ideal electrode material for electrochemical fluorination reactions. The installation of fluorine a to heteroatom-substituted positions can be anodically performed by hydrogen fluoride/triethylamine mixtures. The Fuchigami group studied several electrode materials for the fluorination of oxindole 20. In this transformation to 21 only a... 

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