δ-Keto Aminoacrylonitriles and δ-Keto Aminoenones from 1-Pyrrolines, Cyanoacetylenes, and Acetylenic Ketones

Abstract

The ring-opening/functionalization of 1-pyrrolines by cyanoacetylenes or acetylenic ketones (20-80 oC, MeCN, H2O) affords δ-keto aminoacrylonitriles and δ-keto aminoenones, mostly as the Z-isomers, in up to 85% yields. The synthesis involves the C(2)-N-bond cleavage in the intermediate hemiaminal resulted from the intermediate 1,3(4)-dipolar 1-pyrroline/acetylene complexes and water.

Catalyst-Free Annulation of Acylethynylpyrroles with 1-Pyrrolines: A Straightforward Access to Tetrahydrodipyrrolo[1,2-a:1′,2′-c]imidazoles

“…In this work, we have attempted to extend the synthesis of δ-keto aminoenones from internal acylacetylenes and 1-pyrrolines in the presence of water (Scheme ) over acylethynylpyrroles.…”

A Quantum Chemical Study on the Mechanisms of Acylpyrrolylacetylenes Reactions With 1‐Pyrrolines

“…The formation of 2-hydroxyazolidine structures 8 is considered to be an intermediate step in the reaction of pyrrolines with electron-deficient acetylenes, which proceeds with the opening of the pyrroline ring and the formation of δ-keto aminonenones according to Scheme 1. [4] The direct proton transfer from the hydroxyl group to the pyrrolidine nitrogen atom with opening of the pyrrolidine ring in the isolated molecule 8 (Figure 6) requires a high activation energy ΔG � =30.47 kcal/mol. The introduction of a water molecule into the reaction as a proton carrier does not lower the activation barrier.…”

“…[3] Recent studies have shown that electron-deficient cyanoacetylenes and acetylenic ketones, with an activated triple bond due to an electron-withdrawing substituent, can interact with 1-pyrrolines leading to the formation of δ-keto aminoenones and δ-keto aminoacrylonitriles, as shown in Scheme 1. [4] In particular, such a reaction also takes place when the Nsubstituted 2-pyrrolyl group acts as R 2 . On the contrary, in the case of N-unsubstituted acylpyrrolylacetylene, instead of the expected δ-keto aminoenones, complex structures consisting of three five-membered nitrogen-containing heterocycles are formed (Scheme 2).…”

“…The current interest in functionalized conjugated enaminones is driven by their wide range of applications in the synthesis of heterocyclic ensembles for modern medicinal chemistry and materials science. [4,6] Condensed heterocycle systems containing three five-membered nitrogen heterocycles are attracting attention for their potential pharmaceutical activities, [5] especially for their promising antiviral properties according to in silico evaluations. [7] Here we investigate the reactions' mechanisms by using the interaction of the 1-phenyl-3-(1H-pyrrol-2-yl) prop-2-yn-1-one (1) and 5-methyl-3,4-dihydro-2H-pyrrole (2) in acetonitrile and methanol as an illustrative example.…”

“…Both of these recently discovered reactions are of undoubted value for fundamental organic chemistry and also appear to be promising in terms of practical applications. The current interest in functionalized conjugated enaminones is driven by their wide range of applications in the synthesis of heterocyclic ensembles for modern medicinal chemistry and materials science [4,6] . Condensed heterocycle systems containing three five‐membered nitrogen heterocycles are attracting attention for their potential pharmaceutical activities, [5] especially for their promising antiviral properties according to in silico evaluations [7]…”