Synthesis of Functionalized Pyrroles via Catalyst- and Solvent-Free Sequential Three-Component Enamine−Azoene Annulation

Abstract

A new and efficient synthesis of polysubstituted pyrroles by a sequential one-pot three-component reaction between primary aliphatic amines, active methylene compounds, and 1,2-diaza-1,3-dienes (DDs) is reported. The reactions were performed without catalyst and under solvent-free conditions with complete control of pathway selectivity. Notably, the ready availability of the starting materials and the high level of practicability of the reaction and work up make this approach an attractive complementary method for access to unknown polysubstituted pyrroles.

Transition metal-free one-pot synthesis of nitrogen-containing heterocycles

“…Utilizing the application of 1,2-diaza-1,3-dienes in the synthesis of diverse heterocycles, Attanasi et al [60] achieved the solvent-and catalyst-free synthesis of pyrrole derivatives 61 via the condensation/aza-annulation of 1,2-diaza-1,3-dienes 58, primary aliphatic amines 59, and diketone derivatives 60. Electron-withdrawing groups at R 4 and R 5 including dimethyl-methylphosphonate provided desired products in good to moderate yield (Scheme 20).…”

Synthesis and Cation Recognition Study of Novel Benzo Crown Ether Functionalized Enamine Derivatives

“…Nowdays, enamine and enamine like compounds have important building blocks employed as nucleophile in Michael type addition for the synthesis of natural product, fused heterocycles and precursors of chiral amines upon asymmetric transformations [17][18][19][20] . Amongst them β-enaminones represent a useful moiety for the synthesis of heterocyclic scaffolds such as pyrrole, dihydropyridine, piperidine, pyrimidine etc.…”

Multicomponent one-pot synthesis of highly-functionalized pyrrole-3-carbonitriles in aqueous medium and their computational study

“…For the first time, we report a convenient four component MCR protocol for synthesis of pyrroles using water as a solvent under catalyst-free conditions. 60 In preliminary experiments, the four-component reaction of benzaldehyde (1a-j), malononitrile (2), 3,4-dichlorophenyl isocyanide (3) and morpholine (4) in EtOH and H 2 O as a solvent at room temperature, displayed no reaction (Table 1, entries 1, 5). At increased temperatures (80 o C), using either EtOH or MeOH as the solvents, reaction occurred, but with low yields (Table 1, entries 2, 3).…”

“…Compounds are depicted in sticks format, whereas the amino acids are shown in lines. Hydrogen bonds are shown as green dotted lines while the hydrophobic60 interactions are presented in blue dotted lines. Magnesium metal is shown in pink ball format.…”