A facile route to the synthesis of polyfunctionalized pyrroles

A simple and efficient synthesis of some polyfunctionalized pyrrole derivatives by triphenylphosphine-promoted condensation reaction between dialkyl acetylenedicarboxylates and 1-aryl-2-(arylamino)-2-hydroxyethanones is described.


Introduction
N-Heterocycles receive considerable attention in the literature as a consequence of their exciting biological properties and their role as pharmacophores. 1Of these heterocycles, the pyrrole ring is one of the most fundamental.It is a widely distributed structural unit in a variety of natural and biologically important molecules such as porphyrins, bile pigments, coenzymes, and alkaloids. 2herefore, it is not surprising that many methods for the syntheses of substituted and functionalized pyrroles have been reported in the literature. 3Recently, syntheses of polysubstituted pyrroles have been reported from conjugate addition reactions, 4 transition metal intermediates, 5 reductive coupling, 6 aza Wittig reactions, 7 isocyanide-based reactions, 8 utilizing the sila-Stetter/Paal-Knorr sequence strategy 9 and other useful pathways. 10Three-component reaction between triphenylphosphine, dialkyl acetylenedicarboxylates (DAAD's) and organic acidic compounds is well known to produce phosphorus ylides. 113][14][15] This strategy has been recently utilized for the synthesis of a variety of heterocyclic and carbocylic compounds.In continuation of our previous work on the reaction between trivalent phosphorus nucleophiles and acetylene diesters in the presence of acidic organic compounds, [16][17] in this letter we report a simple and efficient synthesis of some functionalized pyrrole derivatives.Thus, the reaction between 2-hydroxy-1-aryl-2-(arylamino)ethanones 18 1 and dialkyl acetylenedicarboxylates 2 in the presence of triphenylphosphine 3 at ambient temperature in dichloromethane, leads to substituted pyrrole derivatives 4 in good yields (Scheme 1).

Results and Discussion
The structures of compounds 4a-g were deduced from their elemental analyses and their IR, 1 H NMR, 13 C NMR spectra.The 1 H NMR spectrum of 4a was very simple including two sharp singlets for methoxycarbonyl groups (δ= 3.78, 3.89 ppm) supported by the absorption band at 1732 cm -1 in IR the spectrum of 4a.A single signal was observed at δ 7.06 for pyrrole hydrogen and four doublets were appeared at δ 7.34, 7.54, 7.56 and 8.36 ppm for two para-substituted phenyl rings. 13C NMR spectrum of 4a exhibited sixteen distinct signals in consistent with the proposed structure.
On the basis of the well established three-component reaction between acetylene diesters and triphenylphosphine in the presence of organic NH acids, it is reasonable to propose that reaction between triphenylphosphine, DAAD and 2-hydroxy-1-aryl-2-(arylamino)ethanone afforded ylide intermediate 6, which converted to 2,5-dihydropyrrole intermediate 7.This intermediate loses a molecule of water and aromatizes to product 4 under reaction condition (Scheme 2).Scheme 2. Suggested mechanism for formation of compound 4.

Conclusions
In summary, here we report an efficient method for the synthesis of some functionalized pyrrole derivatives by condensation reaction between acetylene diesters and 2-hydroxy-1-aryl-2-(arylamino)ethanones promoted by triphenylphosphine.The advantages of the suggested method are simple reaction conditions, good yields and using starting materials without any activation or modification.

Experimental Section
General.Melting points were determined with an electrothermal 9100 apparatus.Elemental analyses were performed using a Heraeus CHN-O-Rapid analyzer.Mass spectra were recorded on a FINNIGAN-MAT 8430 mass spectrometer operating at an ionization potential of 70 eV.IR spectra were recorded on a Shimadzu IR-470 spectrometer. 1 H and 13 C NMR spectra were recorded on Bruker DRX-500 Avance spectrometer at solution in CDCl3 using TMS as internal standard.The chemicals used in this work purchased from Fluka (Buchs, Switzerland) and were used without further purification.