A Novel Facile Synthesis of 2,5-Di- and 2,3,5-Trisubstituted Pyrroles

Abstract

Heterocyclization of ketoximes with propyne or allene in superbase systems MOR/DMSO (M = K, Cs; R = H, t-Bu), which leads to 2-alkyl(aryl, hetaryl)-5-methyl-and 2,3-dialkyl-5-methylpyrroles or 2-methyl-4,5,6,7-tetrahydroindole in yields of up to 63%, has been accomplished for the first time. The reaction is mostly regioselective affording mainly or exclusively 2,5-di-and 2,3,5-trisubstituted pyrroles. The minor isomers in most cases are the corresponding 2,4-di-and 2,3,4-trisubstituted pyrroles, only in the case of acetoxime the isomer ratio is ca 1:1. For oximes of methyl isopropyl ketone and pinacolone, the 4-methyl-isomers become predominant (78, 83%, respectively).

A Synthetic Methodology for Pyrroles from Nitrodienes

“…2‐(2‐Furyl)‐5‐methyl‐1 H ‐pyrrole (2j): Colorless oil; yield: 62 %. 1 H NMR (400 MHz, CDCl 3 ): δ = 8.23 (br.…”

Zirconocene dichloride catalysed one-pot synthesis of pyrroles through nitroalkene-enamine assembly

“…Several researchers have investigated metal-mediated formation of C-C/C-N bonds in pyrrole synthesis, 6 and various metal salts have demonstrated high efficiencies. [7][8][9][10][11][12][13][14][15][16][17][18][19] Examination of the previous studies illustrates general reaction patterns involving either a cycloisomerization or a cycloaddition in the synthesis of pyrroles. The vast numbers of methods available provide chemists with an arsenal of strategies to choose, depending on the starting materials available or the products desired.…”

Chemistry of heterocyclic compounds at the A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, over 50 years (Review)

“…The propyne-allene/KOH/DMSO system was used successfully for the direct N-isopropenylation of various azoles (pyrroles, pyrazoles, imidazoles, 1,2,4-triazoles) at atmospheric pressure and in an autoclave [182,183].…”

“…Much attention has been paid to the search for convenient methods for functionalization of the pyrrole ring [98,[178][179][180][181][182][183][184][185][186][187][188][189][190][191][192][193][194][195][196]. Thus, the processes involved in the vinylation of indole and other azoles by acetylene (under pressure, at 180-220°C, in the presence of KOH, alkali metals, and their salts with azoles) and also the characteristics of the synthesized N-vinylazoles and their derivatives were actively studied from the very early years (G. G. Skvortsova, E. S. Domnina et al) [171][172][173][174][175][176][177][178][179][180][181].…”