A Domino Route toward Polysubstituted Pyrroles from 2-Imidazolines and Electron-Deficient Alkynes

Abstract

The reaction of 1,2-disubstituted 2-imidazolines with electron-deficient alkynes proceeds as a pseudo-threecomponent process and forms imidazolidines with an N-vinylpropargylamine fragment. Heating the resulting imidazolidines in xylene on air leads to an effective formation of polysubstituted pyrroles through a domino sequence of aza-Claisen rearrangement/ transannular nucleophilic addition/oxidative ring opening reactions. The direct one-pot transformation of 2-imidazolines to pyrroles has been also realized.

Assembly of 1,2,3,4-Tetrahydropyrrolo[1,2-a]pyrazines via the Domino Reaction of 2-Imidazolines and Terminal Electron-Deficient Alkynes

“…According to a previously published procedure, imidazolines 1 were treated with 2 equiv of methyl propiolate ( 2a ) or acetylacetylene ( 2b ) to produce adducts 3a–w in good to excellent yields (Scheme ).…”

“…The most interesting are the examples in which 2-imidazoline ring cleavage leads to the formation of new heterocyclic entities . We have recently developed a synthetic approach for the transformation of 2-imidazolines into monocyclic pyrrole derivatives, “imidazoline to pyrrole” . The interactions of 2-imidazoline with alkynes produce tetrasubstituted imidazolidines, containing an N -vinylpropargylamine fragment.…”

Pd-Catalyzed Triple-Fold C(sp2)–H Activation with Enaminones and Alkenes for Pyrrole Synthesis via Hydrogen Evolution

“…With the catalysis of proper transition metal reagents, stable enamines such as enaminones, enaminoesters, enaminonitriles, etc. have been used to couple alkynes, alkenes, diazoesters/hydrazones, or functionalization of intramolecular C–H bonds for the synthesis of diversely functionalized pyrroles. Interestingly, although a plethora of different alkenes have been successfully used as reaction partners of stable enamines for pyrrole synthesis, no known method has hitherto been found to tolerate the transformation of acrylates for the synthesis of corresponding pyrrole products.…”

X-Yne Click Polymerization

“…Then, the second ethynyl group further attacked the α-position of nitrogen atom, leading to the disubstituted imidazoline. 94 Notably, this reaction could proceed smoothly at room temperature in common aprotic solvents with moderate to high 34 yields. In Scheme 6b, oxime and two molecules of ester-activated alkyne occurred a diastereoselective (up to >99:1) annulation, generating polysubstituted β-lactams.…”