Synthetic methods for γ-lactam and pyrrole derivatives exploiting a three-component coupling strategy

4-Aryloxymethyl-3-pyrrolines and their isomeric pyrrolidines--assembled via a one-pot, three-component coupling of propargylic amines, vinyl sulfones, and phenols--may be elaborated further to provide an easy access to 2,4-disubstituted pyrrole-3-carboxylates and 3,4-disubstituted pyrrolidin-2-ones. The latter were prepared by means of an unprecedented rearrangement process involving hydrogenolysis of 2-aryl pyrrolidine-3-carboxylates, whereas the pyrrole carboxylates arose from aromatization of the corresponding pyrrolines.     

First synthesis of arylpyrrolo- and pyrazolopyrrolizinones as useful agents with potential biological interest

Novel arylpyrrolo- and pyrazolopyrrolizinones were prepared in three or four steps starting from aminoarylpyrrole and pyrazole carboxylates through the cyclisation of a Vilsmeier-Haack intermediate. This synthesis was enhanced by diverse N-protections of the aza-heterocycle and furnish new series with potential biological interest.     

How to Control the Chemoselectivity of the Catalytic Formation of Chiral γ-Lactams or 2,3-Disubstituted Pyrroles by the Choice of Solvent

Summary. The reaction of the unsaturated imine methyl(3-phenylallylidene)amine with ethylene and carbon monoxide in the presence of catalytical amounts of Ru₃(CO)₁₂ leads to the formation of two heterocyclic products. One of the products is a chiral γ-lactam, the other one a 2,3-disubstituted pyrrole derivative, in which only the carbon atom from carbon monoxide is incorporated. The selectivity in the formation of the products may be controlled by the choice of solvent. In general, in nonpolar solvents the formation of the lactam is preferred whereas the use of more polar solvents enhances the yield of the pyrrole. For most of the solvents used there is a linear dependence of the product ratio on the relative permittivity of the corresponding solvent. Typically, polar aprotic solvents do not follow this rule.     

Syntheses of per-N labeled etioporphyrins I-IV and a related tetrahydrobenzoporphyrin for applications in organic geochemistry and vibrational spectroscopy

Nitrogen-15 labeled pyrroles have been prepared from commercially available ¹⁵N glycine or sodium nitrite using the Barton-Zard, Knorr, and Kleinspehn approaches. These pyrroles were used as intermediates in the synthesis of per-¹⁵N labeled porphyrins needed for the analysis and assignment of vibrational spectra for sedimentary porphyrins. Etioporphyrin-I was prepared via pyrromethene intermediates, while etioporphyrins II-V and a related tetrahydrobenzoporphyrin were synthesized via stepwise routes involving the copper(II) mediated cyclization of a,c-biladienes as the key step. Detailed analyses of both the proton and carbon-13 NMR spectra provide nitrogen-15 coupling constants for these important structures.     

Selective one-pot synthesis of substituted pyrrole-3-phosphonates from α-cyanomethyl-β-ketoesters

A one-step synthesis of 5-alkoxypyrrole-3-phosphonates is presented starting from suitable α-cyanomethyl-β-ketophosphonates. The key step in the synthesis involves a one-pot addition and heteroannulation sequence. The zinc perchlorate-catalyzed addition of alcohols to the nitrile carbon of α-cyanomethyl-β-ketophosphonates followed by annulation furnished 5-alkoxypyrrole-3-phosphonates. The addition-annulation process is carried out in the presence of water and 4,5-dihydro-5-oxo-1H-pyrrole-3-phosphonates (pyrrolinones) are obtained in good yields.     

A one-step route to azomethine ylides via chloroiminium salts

A new, one-step procedure for the generation of azomethine ylides, 4 and 20, via chloroiminium salts, 3 and 19, is reported. The generation of the azomethine ylides was confirmed by their trapping with dimethyl acetylenedicarboxylate (DMAD) which, upon spontaneous 1,4-dehydrochlorination, gave the corresponding pyrroles 17 and 21.     

Silver-catalysed hydroamination: synthesis of functionalised pyrroles

It has been shown that functionalised pyrroles can be efficiently prepared using a two-step sequence. This sequence involves the propargylation of secondary enaminones using n-BuLi and propargyl bromide, followed by intramolecular hydroamination catalysed by silver nitrate. The hydroamination can be carried out at room temperature (overnight) or in a domestic microwave oven (60 s).     

A general approach to arylated furans,pyrroles, and thiophenes

A general and practical synthetic method for aryl-substituted five-membered heterocycles has been developed. In the presence of KOH (30%), 1,4-diaryl-1,3-butadiynes undergo the cyclocondensation reaction with water, primary amines, and Na₂S·9H₂O in DMSO at 80 °C to afford 2,5-diarylfurans, 1,2,5-trisubstituted pyrroles, and 2,5-diarylthiophenes in good to high yields. Further studies have disclosed that aryl-substituted five-membered heterocycles can be also synthesized by a one-pot, two-step strategy from the terminal alkynes in DMSO firstly catalyzed by CuCl, and then via addition of KOH to promote the cyclocondensation of 1,3-butadiynes generated in situ.     

Cascade reaction for 3-pyrrolines and pyrroles from nitroallylic acetates and N-mesyl 2-aminoethanones

Cascade reactions of nitroallylic acetates with methanesulfonyl 2-aminoethanones affords either the 3-pyrrolines or the pyrroles in one pot depending on reaction solvents and temperature. A possible mechanism for the entire sequence is proposed.     

Indirect regioselective heteroarylation of indoles through a Friedel-Crafts reaction with (E)-1,4-diaryl-2-buten-1,4-diones

A two-step synthesis of 3-heteroaryl indoles has been developed. The first step of the sequence involves a Friedel-Crafts alkylation of indoles with 1,4-diaryl-2-buten-1,4-diones to give the corresponding indoles bearing a 1,4-dicarbonyl moiety. The reaction is catalyzed by InCl₃ and takes place with good yields. Cyclization of the diones under different Paal-Knorr conditions allows to prepare indoles substituted at the C3 position with 3-furanyl, 3-pyrrolyl- and 3-thienyl moieties.