Indole compounds heterocyclic synthesis, intramolecular

Intramolecular cyclization in perfluoroaromanc systems proves useful for the synthesis of heterocyclic compounds [72] For example, the Fischer indole synthesis, which normally requires the presence of an ortho proton, occurs satisfactonly with an ortho fluonne in theperfluoronaphthalene senes [73] (equation 37)... 

On the other hand, catalysts 1 and 56 have been successfully used by Xiao s group in the enantioselective intramolecular ring-closing Friedel-Crafts-type alkylations of indole- [319] and anilino-tethered [320] a, 3-unsaturated aldehydes, respectively. As depicted in Fig. 2.26, this reaction provides access to the synthesis of a wide variety of heterocyclic compounds in high yields and excellent enantioselechvihes. 

Starting in 1977, Mori and Ban " at Hokkaido University discovered that Pd can catalyze the intramolecular reaction of o-halo-iV-allylanilines to indoles under Heck reaction conditions. It was the first intramolecuar Heck reaction to the synthesis of heterocycles. For example, the compound 1, which was prepared from methyl a-bromocrotonate (3) and 2-bromo-A-acetylaniline 4, was adopted as a starting material. It was treated with Pd(OAc)2 (2 mol%) and PPhs (4 mol%) in the presence of tetramethylethylenediamine (TMEDA, 200 moI%) under a stream of nitrogen at 125 °C for 5.5 h methyl l-acetyl-3-indolyl acetate was obtained in a yield of 43% via an intramolecular Heck... 

Nitrogen-containing heterocycles are also available via intramolecular hetero Diels-Alder reactions. Williams employed an aza diene to prepare a complex polycyclic synthetic intermediate in his synthesis of versicolamide B. Boger reported a tandem intramolecular hetero Diels-Alder/l,3-dipolar cycloaddition sequence for the synthesis of vindorosine. Cycloaddition precursor 137 undergoes an inverse electron demand Diels-Alder reaction to yield 138. This compound decomposes via a retro dipolar cycloaddition to generate nitrogen gas and a 1,3-dipole that completes the cascade by reacting with the indole alkene to afford 139. Seven more steps enable the completion of vindorosine. ... 

More recently, a palladium-catalyzed intramolecular C-H arylation with mesylated compounds was reported by Kalyani and co-workers. A sequential mesylation-arylation protocol using phenols as substrates vras described as well. This method allows for the synthesis of diverse heterocyclic motifs, including dibenzofurans, carbazoles, and indoles, in good yields (Scheme 2.30). The intermolecular aiylations were efficient for the coupling of azoles with electronically diverse mesylates. 

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