Cycloaddition Syntheses from Vinyl Pyrroles

Like the Diels-Alder cycloaddition reaction of 2- and 3-vinylindoles to give carbazoles, the cycloaddition of 2- and 3-vinylpyrroles to give indoles is a well-established methodology [1], 

An excellent 4-acylindole synthesis nsing the Diels-Alder cycloaddition of a 2-(2-phenylsnIfinylvinyl)pyrrole was described by Muchowski and ScheUer (Schane 3, equation 1) [13]. DesilylationoftheTIPS-prolected indoles occurred readily (n-Bu NF, THF, 0 C). The 2-vinylpyirole was prepared from pyrrole in four steps (50% yield). This method provided an excellent synthesis of 4-fonnyIindole (R = = H). Seitz and colleagues reported a synthesis of 

4-bromoindole 3 via the cycloaddition of V-tosyl-2-vinylpyrrole and tetrabromocyclopropene (equation 2) [14], Base treatment of 3 afforded 4-bromo-5-formylindole (30%). Eguchi and coworkers used V-ethoxycarbonyl-2-[(trimethylsilyl)vinyl]pyrrole as the diene in cycloaddition reactions with dienophiles to give indoles or (usually) tet-rahydroindoles (equation 3) [15,16], The yield of indole 4 was increased to 28% if the reaction was run under oxygen. Ketcha and Xiao described the Diels-Alder reactions of both 2- and 3-vinyl-l-(phenylsulfonyl)pyrroles with electron-deficient vinylic dienophiles to give tetrahydroindoles [17]. The vinylindoles were crafted in two steps from the A-phenylsulfonyl 2- and 3-acetylpyrroles. 

Indole Ring Synthesis From Natural Products to Drug Discovery, First Edition. Gordon W. Gribble. 2016 John Wiley Sons, Ltd. Published 2016 by John Wiley Sons, Ltd. 

Yamashita and colleagues reported an indole synthesis absence of Ac O. The pyrrole carbene complex was from pyrrole-carbene chromium complexes reacting with prepared from 2-Uthio-l-methylpyrrole and chromium 

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The first total synthesis of (+/—)-isostemofoline (224) (Scheme 22) was accomplished in 27 steps and in less than 0.1% overall yield from 1,2-hexanediol featuring a [4 + 3] cycloaddition of a substituted iV-Boc pyrrole and a vinyl diazoester, the use of a furyl substituent as a surrogate of a carboxylic acid residue, and the formation of an ( )-conjugate butenolide via dehydration of the corresponding alcohol 81). 

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