2- indole, reaction with methyl propiolate

During synthetic studies on the antitumour antibiotic CC-1065, ready access was required to a series of 6-substituted indole-3-carboxylates. The following example illustrates the successful general strategy that was developed reaction of the N-Cbz derivative of N-(3-methylphenyl)hydroxylamine with methyl propiolate in nitromethane as solvent and in the presence of Hunig s base gave methyl l-benzyloxycarbonyl-6-methylindole-3-carboxylate directly in 89% yield. 

Padwa and coworkers found that a-cyanoaminosilane 12a is a convenient synthon for azomethine ylide 15 which is extensively used in heterocyclic synthesis [7]. AgP has been adopted to generate the ylide 15 from 12a for the preparation of pyrrolidine derivative 14 (Sch. 4). Various dipolarophiles including A-phenylmaleimide (13) can be used for the cycloaddition. When iV-[(trimethylsilyl)methyl]-substituted indole 16 is reacted with AgP in the presence of maleimide 13, pyrrolo[l,2-a]indole 17 is formed in good yield, retaining the CN group [8]. A silver-bonded carbonium ion is assumed to be a reactive intermediate. Reaction of a cyano-substituted azomethine ylide, derived from (silylmethylamino)malononitrile 12b and AgP, with methyl propiolate (18) provides 3-carbomethoxy-A-benzylpyrrole (19) [9]. Epibatidine, a novel alkaloid, was successfully synthesized by employing the [3 + 2] cycloaddition of azomethine ylide with electron-deficient alkenes as a key step [10]. 

Several 2-(2-thienyl) and 2-(3-thienyl)pyrrole-3-carboxylates were made by reaction of acetylthiophene oximes with methyl propiolate or dimethyl acetylene-dicarboxylate. <93JCR(S)210> This reaction is related to other sigmatropic rearrangements which have been used in pyrrole and indole synthesis. 

---