Oxindoles derivatives

Dipolar cycloadditions of the unusual dipolarophiles 9-arylidenefluorenes 446 with the dipoles generated from isatin 432a and cyclic amino acid proline 433a were carried out under four different conditions to yield a series of novel dispiro oxindole derivatives 50a-f via [3+2] cycloaddition (Scheme 100) <2002T8981>. 

The conversion of indole alkaloids to oxindole derivatives has been studied extensively. Since this review does not deal with the literature of oxindole alkaloids, only the most important transformations of the alkaloids having indo-loquinolizine as well as yohimbane skeletons are to be mentioned. 

Scheme 68 2-Oxindol derivatives by nickel-catalyzed cyclization of aryl halides.

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). 

Similar to A-allvlanilincs. their ease of formation makes N-acryloylanilines also an attractive starting material for the preparation of indole derivatives. Acrylates having an cr-substituent give rise to chiral oxindole derivatives, both a common building block of natural products and a frequently employed synthon en route to them.18 By using a chiral palladium-BINAP catalyst Overmann was able to achieve high enantioselectivity in the transformation shown in 3.14.19... 

Arumugam, V. Routledge, A. Abell, C. Balasubramanian, S. Synthesis of 2-Oxindole Derivatives via the Intramolecular Heck Reaction on Solid Support, Tetrahedron Lett. 1997, 38, 6473-6476. 

In a related example, the desired rhodium carbenoid could be generated from 3-substituted indole or oxindole derivatives, which are readily accessible by ytterbium triflate-catalyzed Michael reactions, but several problems were... 

In subsequent work, it was found that the reaction conditions could be modified to give a single product. Thus, carrying out the acid-catalyzed cyclization in the presence of an external source of hydride, such as triethylsilane, led to compound 75 in 92% yield, while the presence of an hydride acceptor such as DDQ resulted in the formation of 76 as the sole product, albeit in 45% yield. Compound 77 was finally transformed into the oxindole derivative 79 by oxidation with W-bromosuccinimide in the presence of ferf-butyl alcohol (Scheme 17). 

When heated in acidic medium the oxindole derivatives 178 (R = H) undergo recyclization to 2-aryl-1,4-dihydro-4-quinolinecarboxylic acids 179 or to 2-phenyl-4-quinolinecarboxylic acid (cinchophen) [151],... 

Selective indole oxidation is not an easy task and usually requires several steps with conventional synthetic organic methods. Here again, CPO allows the synthesis of oxindoles with high yields and selectivity [68, 69]. The key of the selectivity is the direct oxygen transfer from compound I to the substrates, yielding the oxindole derivative with substituted indoles, the yield is nearly quantitative (Fig. 6.6). 

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). 

Orally administrable nonpeptide oxindole derivatives, (HI), prepared by Tokunago (4) were effective in stimulating the release of growth hormone factor. 

Fluoro-2-oxindole derivatives, (IV), prepared by Dworetzky (5) were effective modulators of KCNQ potassium channels and used in treating migraine and mechanistically related disease. 

A method of treating aberrant cellular proliferation disorders by the selective inhibition of the tyrosine family of protein kinases (TrkA, TrkB, and TrkC) using oxindole derivatives is described. This novel chemical art is an improvement over the existing treatment agents in that the materials are selective tyrosine kinase inhibitors and are prepared in one step. 

Oxindole derivatives, (III), prepared by Harris (3) were effective as Trk family protein tyrosine kinase inhibitors and were useful in cancer therapy. 

Annulation of the carbamoyl chloride 165 into the oxindole derivative 166 (Equation 52) illustrates an approach that has also been used for the construction of several related molecules <2000CC2239>. 

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