Multicomponent Tether Catalysis Synthesis of Highly Functionalized 4-(Pyridin-2-ylmethyl)-2-aminopyrroles via Cascade Reaction Is Accompanied by Decarboxylation

Abstract

A multicomponent tether catalysis protocol for the synthesis of 4-(pyridin-2-ylmethyl)-2-aminopyrroles (PMAPs) was constructed by simply refluxing a mixture of ethyl 2-(pyridin-2-yl)acetates 1 and various types of arylglyoxal monohydrates 2 and different heterocyclic ketene aminals 3 in EtOH solvent. Based on this reaction, a series of highly functionalized PMAPs were obtained through a novel cascade reaction accompanied by a decarboxylation mechanism. As a result, the pyridin-2-ylmethyl was successfully introduced in the target compounds, and a library of PMAPs were easily constructed using the cascade reaction described in this study. This protocol demonstrated that the most important feature was the decarboxylation reaction of the 2-(pyridin-2-yl)acetates 1, which can be used in the synthesis of pyridin-2-ylmethylsubstituted heterocycles, including pyrroles, pyridines, quinolones, and other heterocyclic compounds resembling those found in nature.

Multicomponent Cascade Reaction by Metal-Free Aerobic Oxidation for Synthesis of Highly Functionalized 2-Amino-4-coumarinyl-5-arylpyrroles

“…EDAMs 2 and 3 were synthesized by known literature procedures. , All the other chemicals used in the experiment were purchased from commercial sources and were used without further purification.…”

Recent Advancements in Pyrrole Synthesis

“…Another example of the use of arylglyoxal is the multicomponent tether catalysis that was reported by Yan. [98][99][100][101] The protocol in this chemistry involved a simple mixing of Zhong and Chen reported a DABCO-promoted threecomponent domino reaction using arylglyoxal monohydrates, enamino esters 209, and 1,3-dicarbonyl compounds to give highly functionalized NH-pyrrole adducts 210 (Scheme 23). 102 This reaction commences with the Knoevenagel-type condensation between arylglyoxal and the 1,3dicarbonyl compound in the presence of catalytic DABCO, thereby producing ,-unsaturated intermediate 211, which serves as a Michael acceptor to electron-rich enaminone 209; cyclization then generates pyrrole 210.…”

“…Another example of the use of arylglyoxal is the multicomponent tether catalysis that was reported by Yan. [98][99][100][101] The protocol in this chemistry involved a simple mixing of ethyl 2-(2-pyridyl)acetates 201, arylglyoxal monohydrates 202, and heterocyclic ketene aminals (HKA) 203 in ethanol at reflux. The mechanism is proposed via pyridinium addition intermediate 205, leading to tethered catalysis intramolecular cyclization to furnish 1,4-keto ester 206.…”

Palladium catalysed, three-component cascade reaction for the efficient synthesis of diverse small molecules

“…One-pot multicomponent reactions (MCRs) are a powerful method for synthesizing complex molecular scaffolds in a single step. [1][2][3] Advantages in using MCRs over a linear reaction sequence to afford the same molecule include better yields, ease of synthetic access to analogues, and a single purification step.…”