Pyrrole continued electrophilic substitution

Nevertheless, this collection of heterocycles does share certain characteristics. The trend we have seen of decreasing tendency towards electrophilic substitution on going from furan, pyrrole, and thiophene to the azoles is continued into these series. The presence of additional pyridine-like nitrogen atoms renders these systems particularly electron-deficient, and electrophilic substitution is of little importance. 

Organometallic intermediates continue to be important in the synthetic methodology for substitution of pyrroles and indoles. Numerous lithiation techniques have been reported and provide a range of useful reaction conditions. The pyrrolyl dimer (120) (really a dimeric equivalent of pyrrole-2-carbaldehyde) can be lithiated at the 5- and 5 -positions. Electrophilic substitution then yields 5-substituted pyrrole-2-carbaldehydes (121) (Scheme 34) <88TL777>. The related monomeric ald-iminium salts (122) yield similar products after anion formation, bromination, lithiation, and electrophilic attack (Scheme 35) <88HCA2053>. In a similar process, the dimer (120) can be brominated at C-4 and converted into 4-substituted pyrrole-2-carbaldehydes <88TL3215>. 

Lanthanide based Lewis acids continue to play pivotal roles in expediting electrophilic substitution reactions of both pyrroles and indoles vide infra). To the point, pyrroles (e.g., 63) have been found to undergo efficient conjugate addition with electron deficient olefins 66 in the presence of a catalytic amount of indium trichloride to afford the Michael adducts 67 <01TL8063>. 

Electrophilic Substitution.—Quantitative aspects of the electrophilic substitution of furan, thiophen, pyrrole, and other five-membered heteroaromatic systems are treated in a review by Marino. Gol dfarb and his school are continuing their extensive work on electrophilic substitution in simple thiophens. The action of benzoyl chloride on 2-acetylthiophen in an excess of aluminium chloride at 110—115 °C without solvent gave a complex mixture of 2-benzoylthiophen,... 

Electrophilic reactions on the electron-rich, aromatic thiophene nucleus continue to provide a powerful route to substituted derivatives. Comparison of positional selectivity of the heteroarenium ions derived from furan. pyrrole or thiophene suggest that ease of P-substitution correlates with the relative stabilities <94H2029>. Freidel-Crafts reaction of 2,5-... 

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