Organocatalytic Mannich/cyclization/aromatization sequence: direct synthesis of substituted pyrrole-3-carboxaldehydes

Catalyst-free direct regiospecific multicomponent synthesis of C3-functionalized pyrroles

“…Aqueous succinaldehyde 1 (3M solution) was prepared using the reported procedure. 28 The reactions under the standard conditions were monitored by thin-layer chromatography (TLC) on Merck silica gel 60 F254 pre-coated plates (0.25 mm). Column chromatography purification was performed on silica gel (100–200 mesh) using a mixture of petroleum ether/EtOAc.…”

Recent approaches in the organocatalytic synthesis of pyrroles

“…In 2012, Kumar et al developed a robust two-step strategy involving the reaction of succinaldehyde 93 with N -PMP aldimines 94 in the presence of organocatalyst 4 in DMSO at room temperature, followed by acid-catalyzed cyclization and aromatization under the influence of DDQ in toluene at 70 °C for the synthesis of substituted pyrroles 95 in 58–82% yield ( Scheme 27 ). 39 This transformation was completed through the formation of an enamine intermediate 96 from the reaction of succinaldehyde 93 and amine catalyst 4, which reacts with the N -PMP aldimines 94 via a direct Mannich reaction, followed by intramolecular cyclization with the simultaneous regeneration of 4, acid-catalyzed dehydration and final aromatization by DDQ with a subsequent loss of the water molecule to provide the pyrroles 95.…”

Acid-induced intermolecular [3+2] cycloaddition/oxidation to synthesize polysubstituted benzo[f]isoindole-4,9-diones

“…Due to their wide utility as biologically active agents and key intermediates in organic synthesis, pyrrole derivatives have attracted significant attention from organic chemists, and a variety of efficient methods have been developed for their synthesis. Examples include Hantzsch, [13][14][15][16][17][18] Trofimov, [19][20][21][22] Mannich [23][24][25][26] and Clauson-Kaas reactions, [27][28][29][30] Friedel-Crafts, [31][32][33][34] and [3+2] cycloadditions. [35][36][37][38][39] In recent years, metal-free catalysis of various organic transformations has gained more and more attention.…”