Transition-Metal-Free Synthesis of Pyrrolo[1,2-a]pyrazines via Intramolecular Cyclization of N-Propargyl(pyrrolyl)enaminones

Abstract

A concise transition-metal-free strategy for the synthesis of pyrrolo[1,2-a]pyrazines with enone substituents has been developed. It includes the following key steps: (a) cross-coupling of pyrroles with acyl(bromo)acetylenes in solid alumina at room temperature to give 2-(acylethynyl)pyrroles; (b) addition of propargylamine to the above acetylenes to form the corresponding N-propargylenaminones; and (c) chemo- and stereoselective base-catalyzed (Cs2CO3/DMSO) intramolecular cyclization of the synthesized propargylic derivatives to form (acylmeth­ylidene)pyrrolo[1,2-a]pyrazines of Z-configuration.

Pyrrole–Aminopyrimidine Ensembles: Cycloaddition of Guanidine to Acylethynylpyrroles

“…2-Acylethynylpyrroles 1a,f – l,n – r were obtained from pyrroles and 2-acylbromoacetylenes accordingly to methodology [ 40 , 41 , 42 ]. Physico-chemical characteristics 2-acylethynylpyrroles 1a,f – l,n – r were given in [ 40 , 43 , 44 , 45 , 46 , 47 ]. 2-Acylethynylpyrroles 1b,c – e,m,s – v were obtained accordingly to the following procedure:…”

“…Acylethynylpyrroles 1a,f-l,n-r were obtained from pyrroles and 2-acylbromoacetylenes accordingly to methodology[40][41][42]. Physico-chemical characteristics 2-acylethynylpyrroles 1a,f-l,n-r were given in[40,[43][44][45][46][47]. 2-Acylethynylpyrroles 1b,c-e,m,s-v were obtained accordingly to the following procedure:The corresponding pyrrole (1 mmol) and acyl(bromo)acetylene (1 mmol) were carefully ground in a porcelain mortar with alumina [10-fold amount by weight of combined mass of pyrrole and acyl(bromo)acetylene] at 20-25 • C for 5 min.…”

Pyrrole-Based Enaminones as Building Blocks for the Synthesis of Indolizines and Pyrrolo[1,2-a]pyrazines Showing Potent Antifungal Activity

“…Although pyrrolo [1,2-a]pyrazines have received less attention from researchers than indolizines, their broad spectrum of activity has stimulated the discovery of versatile synthetic strategies [1,2]. One of the most efficient approaches involves pyrrole-containing substrates, which undergo a cyclization process to build the pyrazine ring [20][21][22][23][24] (Scheme 1a). Indolizines have been prepared by following an analogous methodology, starting from functionalized pyrroles as the building block and completing the synthesis by a proper annulation to build the six-membered ring [25][26][27][28][29] (Scheme 1b).…”

Base‐Promoted Formation of an Annelated Pyrrolo‐1,4‐oxazine Ensemble from 1H‐pyrrol‐2‐ylmethanol and Propargyl Chloride: A Theoretical and Experimental Study

“…Consequently, the rational strategy for the construction of annelated pyrrole ensembles involves cyclization of functional groups introduced in advance into the pyrrole ring. [10][11][12][13] Such a strategy affords sufficient flexibility in the synthesis of the second heterocycle. In addition, by varying the substituents at other positions of the initial pyrrole molecule, one can obtain wide series and libraries of compounds for further studies.…”

“…The highly reactive pyrrole molecule is easily functionalized at both the α‐position and the nitrogen atom. Consequently, the rational strategy for the construction of annelated pyrrole ensembles involves cyclization of functional groups introduced in advance into the pyrrole ring . Such a strategy affords sufficient flexibility in the synthesis of the second heterocycle.…”