Skeletally Tunable Seven-Membered-Ring Fused Pyrroles

Abstract

We describe a copper-mediated method that enables the synthesis of seven-membered-ring fused pyrroles (7-mrFPs). The protocol proceeds via an in situ spiro-intermediate ring expansion and tolerates a library of 7-mrFP derivatives with a broad range of functional groups in a simple step with tangible parameters and substrate adaptations. These rare 7-mrFPs are now accessible on a millimolar scale, and selected examples exhibit high antioxidant activity.

Recent synthetic journey on pyrrole-fused compounds

“…Ioannis N. Lykakis and group synthesized a 7-membered b-fused pyrrole derivative in one step using a Cu-complex as the catalyst ( Scheme 38 They also investigated the reaction scope using different solvents such as MeOH, EtOH, acetonitrile, THF, toluene, and DCE, where solvents such as MeOH, EtOH and acetonitrile demonstrated better results. After DFT analysis, the mechanistic pathway was proposed as the three-component condensation reaction occurring in situ by the Cu-mediated catalyst to form spiro-intermediate 92aa, followed by ring-expansion, which led to the successful production of 93, whereas Michael addition with the unreacted nitro-alkene generated the fused product 94.…”

“…After DFT analysis, the mechanistic pathway was proposed as the three-component condensation reaction occurring in situ by the Cu-mediated catalyst to form spiro-intermediate 92aa, followed by ring-expansion, which led to the successful production of 93, whereas Michael addition with the unreacted nitro-alkene generated the fused product 94. 38 There is no evidence of alkyl migration leading to the desired product with respect to the spiro-intermediate and controlled experiments were excluded from this study. Also, given that they specifically used a,b-unsaturated nitro compounds, this publication lacks information about other electron-withdrawing group-containing Michael acceptors.…”

Polyoxometalate-Driven Ease Conversion of Valuable Furfural to trans-N,N-4,5-Diaminocyclopenten-2-ones

“…Considering all of the above and given our expertise in developing the synthesis of N -heterocyclic molecules, − as well as POM-based catalytic protocols, , we hypothesized that POMs would be a suitable vehicle to facilitate this domino transformation. In this study, we report, to the best of our knowledge, the first protocol that utilizes POMs for the synthesis of an extended library of trans -DACPs under mild conditions.…”

Visible-Light-Mediated Synthesis of Thio-Functionalized Pyrroles

“…Due to their diverse applications, the synthesis of substituted pyrroles has been an impressive area of research for the scientific community. Besides the conventional Paal–Knorr and Hantzsch syntheses, there are other well-established methodologies for the synthesis of such heterocycles . For instance, Wu and co-workers reported a Cu-catalyzed oxidative annulation for the synthesis of pyrrole-2-carbaldehydes from aryl methyl ketones, arylamines, and acetoacetate esters (Scheme a) .…”