Oxindoles from 2 molecules

The perfluoroacetamide catalysts, rhodium(II) trifluoroacetamidate [Rh2(tfm)4] and rhodium(II) perfluorobutyramidate [Rh2(pfbm)4], are interesting hybrid molecules that combine the features of the amidate and perfluorinated ligands. In early studies, these catalysts were shown to prefer insertion over cycloaddition [30]. They also demonstrated a preference for oxindole formation via aromatic C-H insertion [31], even over other potential reactions [86]. In still another example, rhodium(II) perfluorobutyramidate showed a preference for aromatic C-H insertion over pyridinium ylide formation, in the synthesis of an indole nucleus [32]. Despite this demonstrated propensity for aromatic insertion, the perfluorobutyramidate was shown to be an efficient catalyst for the generation of isomtinchnones [33]. The chemoselectivity of this catalyst was further demonstrated in the cycloaddition with ethyl vinyl ethers [87] and its application to diversity-oriented synthesis [88]. However, it was demonstrated that while diazo imides do form isomtinchnones under these conditions, the selectivity was completely reversed from that observed with rhodium(II) acetate [89, 90]. 

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. 

Aside from the oxindole fragment of the molecule, this formulation was largely speculative the presence of an A-methyl group and a terminal double bond was well founded, but there was no incontrovert-... 

Gelseverine, C21H24-26N2O3, is the tertiary base isolated from the minor alkaloids of Gelsemium sempervirens. It has not yet been obtained crystalline but can be characterized as its perchlorate, mp 250°-252°, or methiodide, mp 259°-261°. The molecule contains one methylimino group and two methoxyl groups, but no C -methyl groups. The UV- and IR-spectra are consistent with its formulation as a 1,3,3-trisubstituted oxindole derivative (18). 

Two ° independent and different degradations have been carried out to establish the absolute stereochemistry, and in each case the final compound contained only the C(3a) asymmetric centre. One approach was to degrade the alkaloid to the oxindole (10), the enantiomorph of which was then synthesised starting from (R)-( — )-2-methyl-2-phenylbutyric acid. In the second approach the molecule was broken down to an amino-acid (11) which was characterised as its 2,4-dinitrophenyl derivative. Its enantiomer was synthesised from 3-ethyl-3-methoxycarbonyl-3-methylpropionic acid of known absolute configuration. 

Monoterpenoid Alkaloids. — Corynantheine - Heteroyohimbine - Yohimbine Group, and Related Oxindoles. Details of the AT-ray crystal structure determination of borreline (92) have now been published,and the species from which it was isolated has been identified as Borreria capitata R. et P. A second alkaloid from this species, borrecapine (93), has a similar structure but, in place of the second methyl group in borreline, borrecapine contains an isobutenyl group which completes the monoterpenoid unit of the non-tryptamine part of the molecule. 

Aiming at die formation of the C/Dring junction by the intramolecular attack of a stabilized allylic anion on an aryne generated from the A ring, the oxindole obtained from 5-bromoisatin was transformed to a mixture of stereoisomers which were further converted to the target molecule. 

An interesting palladium-catalyzed cascade reaction leading to 3,3-disubstituted oxindoles 190 starting from 2-(alkynyl)aryl isocyanates 189 with benzylic alcohols has been developed by Toyoshima et al. [76] (Scheme 6.53). This reaction integrates a cyclization step and a novel [1,3] rearrangement step. Both benzylic and allylic alcohols could be introduced efficiently to this domino process. Furthermore, the products of this reaction are an important class of heterocycles which are often found in naturally occurring and biologically active molecules. 

---