V-Acetylindole

Prior to his work with internal alkynes, Larock found that o-thallated acetanilide undergoes Pd-catalyzed reactions with vinyl bromide and allyl chloride to give (V-acetylindole and N-acetyl-2-methylindole each in 45% yield [409]. In an extension to reactions of internal alkynes with imines of o-iodoaniline, Larock reported a concise synthesis of isoindolo[2,l-a]indoles 313 and 314 [410]. The regioselectivity was excellent with unsymmetrical alkynes. 

Indole reacts with dimethylacetylene dicarboxylate giving tetramethylcar-bazol-l,2,3,4-tetracarboxylate as a major product,formed via 384 (R = H, and/or geometric isomer) and then Diels-Alder addition and dehydrogenation. /V-Acetylindole undergoes an extraordinary double condensation and cyclization with methyl acrylate in the presence of palladium(II) acetate in acetic acid giving 9% of the dimethyl 9-acetylcarbazole-2,3-dicar-boxylate 393 as well as 394 and 395, the products of monosubstitution at the indole a and S-positions. ... 

Variable E/Z ratios have been reported for V-acetylindole (77RRC471), yet the molecule should be predominantly in the Z conformation (> 90%), as suggested by Elguero and co-workers (750MR(6)445). The energy barrier for this derivative has not yet been determined, owing to the very low abundance of one of the conformers. 

Indole only reacts with acetic anhydride at an appreciable rate above 140 °C, giving 1,3-diacetylindole predominantly, together with smaller amounts of N- and 3-acetylindoles 3-acetylindole is prepared by alkaline hydrolysis of product mixtures. That /3-attack occurs first is shown by the resistance of 1-acetylindole to C-acetylation, but the easy conversion of the 3-acetylindole into 1,3-diacetylindole. In contrast, acetylation in the presence of sodium acetate, or 4-dimethylaminopyr-idine, affords exclusively /V-acetylindole, probably via the indolyl anion (section 17.4). Trifluoroacetic anhydride, being much more reactive, acylates at room temperature, in dimethylformamide at C-3, but in dichloromethane at nitrogen. ... 

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