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

Abstract

A novel approach has been constructed for the synthesis of two types of 2-amino-4-coumarinyl-5-arylpyrroles (ACAPs, 5 and 6) through a cascade reaction and a metal-free catalyzed aerobic oxidation reaction of arylglyoxal monohydrates 1, 1,1-enediamines (EDAMs) 2 and 3, and 4-hydroxy-2H-chromen-2-ones 4 via multicomponent reactions to produce the target compounds with good to excellent yields. Specifically, hydroxyl-substituted 2-amino-4-coumarinyl-5-arylpyrroles, that is, 2-amino-4-coumarinyl-5-aryl-6-hydroxylpyrroles (ACAHPs) 6, were obtained by metal-free aerobic oxidation in 1,4-dioxane at simple reflux for approximately 10 h. As a result, ACAHPs 6 have been produced without metal catalysts or traditional oxidizing agents. This method represents a route to obtain the novel ACAPs in an environmentally friendly, concise, rapid, and practical manner with potential biological activity of the product.

Synthetic Access to α-Oxoketene Aminals by the Nucleophilic Addition of Enol Silane-Derived Palladium(II) Enolates to Carbodiimides

“…Consistent with numerous examples in the literature, the frequent deployment by contemporary organic chemists of α-oxoketene aminal intermediates as synthetic precursors to access a range of unique and complex heterocyclic compounds (e.g., pyrimidopyrrolopyridazines, benzo­[ f ]­imidazo­[2,1- a ]­[2,7]­naphthyridines, functionalized indoles, tetrahydroimidazo­[1,2- a ]­pyridines, spiro-oxindole, and 9-azabicyclo[3.3.1]­nonane derivatives) has rendered this motif as a versatile building block in organic synthesis. − α-Oxoketene aminal derivatives are most commonly prepared by the nucleophilic substitution of α-oxoketene dithioacetals with amines, as depicted by the representative example presented in Scheme , eq 1. − However, this specific methodology requires the preparation of α-oxoketene dithioacetal substrates that are typically obtained from ketone starting materials using CS 2 and a methylating agent (MeI or Me 2 SO 4 ) in the presence of a strong base (e.g., NaOH and NaH), a reaction protocol that has limited the potential for widespread application because of the use of toxic and/or volatile reagents . Alternatively, N , N ′-disubstituted ketene aminals can be derived from active methylene compounds (e.g., ethyl cyanoacetate) in a one-pot, two-step synthetic procedure involving treatment with NaH and an isothiocyanate to obtain an N , S -acetal intermediate, which is subsequently coupled with an amine in the presence of a thiocarbonyl activating reagent like EDCI (Scheme , eq 2) .…”

An Environmentally Benign Multicomponent Cascade Reaction of 3-Formylchromones, 2-Naphthols, and Heterocyclic Ketal Aminals: Site-Selective Synthesis of Functionalized Morphan Derivatives

“…The 3-formylchromones 1 and 2-naphthol 2 were commercially available reagents. The heterocyclic ketene aminals (HKAs) 3 were synthesized by known literature procedures . All of the other chemicals used in the experiment were purchased from commercial sources and used without further purification.…”

4‐Hydroxycoumarin: A Versatile Substrate for Transition‐metal‐free Multicomponent Synthesis of Bioactive Heterocycles

“…In 2020, Zi and co‐workers reported a straightforward multicomponent cascade strategy for the synthesis of a vast array of pyrrolyl‐coumarin hybrids (Scheme 4). [44] Initial optimization for the reaction condition revealed that the catalyst‐free condition was best for the reaction. Under this condition, the three‐component cascade reaction of 4‐hydroxycoumarin 17 , arylglyoxal 26 , and substituted enediamines 27 were found to deliver the desired pyrrolyl‐coumarin hybrid 28 in 80–94% yield.…”