Polysubstituted Pyrroles Research Articles

Ruthenium-Catalyzed [3 + 2] Cycloaddition of 2H-Azirines with Alkynes: Access to Polysubstituted Pyrroles.

A ruthenium-catalyzed intermolecular [3 + 2] cycloaddition of 2H-azirines and activated alkynes is reported, which provides polysubstituted pyrroles in moderate to good yields. This approach features a C-N bond cleavage of 2H-azirines by a ruthenium catalyst. The results of this study would provide a complementary method to synthesize polysubstituted pyrroles from the known 2H-azirine approaches and advance 2H-azirine chemistry.

ChemInform Abstract: Base‐Promoted Intramolecular Cyclization of N‐Alkyl, N‐Propargylic β‐Enaminones for the Synthesis of Polysubstituted Pyrroles.

An efficient, mild, metal-free, base-mediated intramolecular cyclization of N-alkyl, N-propargylic β-enaminones has been realized for the generation of polysubstituted pyrrole derivatives. This synthetic transformation tolerates a range of substituted N-alkyl, N-propargylic β-enaminones in moderate to good yields.

Brønsted Acid Catalyzed Selective Cyclization Reaction: An Efficient and Facile Synthesis of Polysubstituted Imidazole and Pyrrole Derivatives

An efficient and facile synthesis of 3-(5-aryl-1,3-dimethyl-2-oxo-2,3-dihydro-1H-imidazol-4-yl)indolin-2-one and 3-(2,5-diaryl-3-oxo-1,2,3,6-tetrahydropyrrolo[2,3-c]pyrazol-4-yl)indolin-2-one derivatives is reported from the selective cyclization reaction of 3-(2-aryl-2-oxoethylidene)indolin-2-one and 1,3-dimethylurea or 5-amino-2-phenyl-2,4-dihydro-3H-pyrazol-3-one under Bronsted acid conditions. Although there are two carbonyl groups in the substrate, the carbonyl group out of isatin is specially chosen for the cyclization reaction to give the target products. The reported products are new five-membered heterocyclic compounds and the results also show that p-toluenesulfonic acid monohydrate (PTSA·H2O) is an effective catalyst for this synthesis. Therefore, the advantages of this approach are excellent yields, short reaction times, operational simplicity, and good regioselectivity.

Synthesis of Polysubstituted Pyrroles through the Tandem 1,3‐Addition/5‐endo‐dig Cyclization of 1‐(1‐Alkynyl)cyclopropyl Imines

Cyclopropyl‐tethered 3‐alkynyl imines react with polarized‐covalent‐bond‐containing compounds to give polyfunctionalized pyrroles. This provides a mild and effective method for the simultaneous introduction of halogen, chalcogen, or hydrogen groups to the 3‐position of the pyrrole ring, together with the incorporation of halogen, azide, or alkoxy/aryloxy groups into the ethyl side‐chain.

Regioselective Iodine-Catalyzed Construction of Polysubstituted Pyrroles from Allenes and Enamines.

A novel I2-catalyzed tandem Michael addition/oxidative annulation of allenes and enamines for the construction of polysubstituted pyrroles has been developed. This protocol represents an efficient and highly regioselective way to access functionalized pyrroles in moderate to excellent yields under mild conditions.

New regioselective synthesis of polyfunctionalized 3-ferrocenyl-1H-pyrroles under microwave irradiation

A facile and regioselective synthesis of a series of new methyl 3-ferrocenyl-1H-pyrrole-2-carboxylates obtained from methyl ferrocenyl azido acrylate and symmetrical or non-symmetrical 1,3-dicarbonyl compounds under microwave-assisted conditions is reported. 3-Ferrocenyl substituted pyrroles, which are normally difficult to obtain via the known reported methods, can now be regioselectively prepared by this protocol. Compared to already known acidic, basic, or metal-catalyzed methodologies for polysubstituted pyrrole synthesis, the present synthetic route is mild, quick, simple, and it furnishes new functionalized tetrasubstituted-pyrroles in short reaction times (30min) and at satisfactory to good yields (32–75%).

Investigation and Application of Amphoteric α-Amino Aldehyde: An in Situ Generated Species Based on Heyns Rearrangement.

In situ generation of the reactive amphoteric α-amino aldehyde with simple α-hydroxy ketones and phenylamine via Heyns rearrangement was proven to be feasible. Metal-free domino reactions based on this reactive intermediate were effectively used to afford important N-heterocycles including polysubstituted pyrroles, indoles, and quinoxalines conveniently. A simple starting material, water as the only byproduct, and diversity of the useful products will make this method greatly attractive for pharmaceutics.

Synthesis of Spiro-lactams and Polysubstituted Pyrroles via Ceric Ammonium Nitrate-Mediated Oxidative Cyclization of N-Furan-2-ylmethyl-β-Enaminones.

Spiro-lactams and polysubstituted pyrroles were synthesized by reactions of furfurylamines with ynones followed by oxidation. Specifically, the protocol involved in situ generation of N-furan-2-ylmethyl-β-enaminones and their subsequent oxidation by ceric ammonium nitrate (6 equiv for spiro-lactam formation, 3 equiv for pyrrole formation). This useful dearomatizing oxidation, which likely proceeds via a free-radical pathway, can be expected to extend the synthetic applications of furan and pyrrole derivatives.

From Aryl Iodides to 1,3-Dipoles: Design and Mechanism of a Palladium Catalyzed Multicomponent Synthesis of Pyrroles.

A palladium-catalyzed multicomponent synthetic route to polysubstituted pyrroles from aryl iodides, imines, carbon monoxide, and alkynes is described. To develop this reaction, a series of mechanistic studies on the [Pd(allyl)Cl]2/P(t)Bu3 catalyzed synthesis of imidazolinium carboxylates from aryl iodides, imines, and carbon monoxide were first performed, including model reactions for each individual step in the transformation. These show that this reaction proceeds in a concurrent tandem catalytic fashion, and involves the in situ formation of acid chlorides, N-acyl iminium salts, and ultimately 1,3-dipoles, i.e., Münchnones, for subsequent cycloaddition. By employing a Pd(P(t)Bu3)2/Bu4NCl catalyst, this information was used to design the first four-component synthesis of Münchnones. Coupling the latter with 1,3-dipolar cycloaddition with electron deficient alkynes or alkenes can be used to generate diverse families of highly substituted pyrroles in good yield. This represents a modular and streamlined new approach to this class of heterocycles from readily accessible starting materials.

Chemodivergent, One-Pot, Multi-Component Synthesis of Pyrroles and Tetrahydropyridines under Solvent- and Catalyst-Free Conditions Using the Grinding Method.

A highly efficient, chemoselective synthesis of a library of polysubstituted pyrroles and tetrahydropyridines has been achieved through the one-pot, multicomponent reactions of ethyl (E)-3-(aryl/alkyl amino) acrylates, 2,2-dihydroxy-1-arylethan-1-ones, and malononitrile under solvent- and catalyst-free grinding conditions. The selective formation of pyrrole or tetrahydropyridines relied on substitution of the N-aryl of ethyl (E)-3-(4-arylamino) acrylates. These reactions presumably occurred via a domino Knoevenagel condensation and Michael addition followed by an intramolecular cyclization sequence of reactions in a single transformation.

Silver(I)-Catalyzed Atroposelective Desymmetrization of N-Arylmaleimide via 1,3-Dipolar Cycloaddition of Azomethine Ylides: Access to Octahydropyrrolo[3,4-c]pyrrole Derivatives.

A highly efficient Ag(I)-catalyzed atroposelective desymmetrization of N-(2-t-butylphenyl)maleimide via 1,3-dipolar cycloaddition of in situ generated azomethine ylides has been established successfully, affording a facile access to a series of biologically important and enantioenriched octahydropyrrolo[3,4-c]pyrrole derivatives in generally high yields (up to 99%) with excellent levels of diastereo-/enantioselectivities (up to 99% ee, >20:1 dr). Subsequent transformations led to fascinating 2H-pyrrole and polysubstituted pyrrole compounds without loss of stereoselectivity. The absolute configuration of the generated chiral axis has been unambiguously identified as (M) through single-crystal X-ray diffraction analysis. Furthermore, on the basis of the comprehensive experimental results and the absolute configuration of one of the cycloadducts, the origin of the stereoselectivity was proposed to be attributed to the steric congestion imposed by the bulky PPh2 group of the chiral ligand and the tert-butyl group of N-(2-t-butylphenyl)maleimide. The possible hydrogen bond interaction between the NH2 group of the chiral ligand and one of the carbonyl groups of N-(2-t-butylphenyl)maleimide is considered to facilitate stabilizing the transition state.

ChemInform Abstract: Organocatalytic Multicomponent Synthesis of Polysubstituted Pyrroles from 1,2‐Diones, Aldehydes and Arylamines.

We have developed an organocatalyzed three-component reaction of 1,2-diones, aldehydes and arylamines, which provides an efficient approach to access polysubstituted pyrroles. In the catalysis of 4-methylbenzenesulfonic acid monohydrate, the reactions of a wide range of 1,2-diones, arylamines and aldehydes took place smoothly to generate the corresponding polysubstituted pyrroles in acceptable to good yields under mild reaction conditions.

ChemInform Abstract: Synthesis of α‐Enamino Esters via Cu(II)‐Promoted Dehydrogenation of α‐Amino Acid Esters: Application to the Synthesis of Polysubstituted Pyrroles.

AbstractA novel and efficient approach towards α‐amino esters as synthons for polysubstituted NH pyrroles is presented.

Convenient synthesis of polysubstituted pyrroles and symmetrical and unsymmetrical bis-pyrroles catalyzed by H3PW12O40

A mild and environmentally-benign protocol for the efficient synthesis of polysubstituted pyrroles via a one-pot three-component reaction of amines, α-bromo ketones and dialkyl acetylenedicarboxylate using H 3 PW 12 O 40 as a recyclable heterogeneous catalyst under solvent-free conditions at room temperature is reported. Importantly, the synthesis of symmetrical and unsymmetrical polysubstituted bis-pyrroles has been performed in good yields for the first time, which can be considered as a salient feature of this protocol. A mild and environmentally-benign protocol for the synthesis of polysubstituted pyrroles, and symmetrical and unsymmetrical bis-pyrroles in the presence of H 3 PW 12 O 40 as a non-corrosive, inexpensive and reusable catalyst under solvent-free conditions at room temperature is reported.

A one-pot sequential five-component domino reaction for the expedient synthesis of polysubstituted pyrroles

A new protocol towards the synthesis of polysubstituted pyrroles via enaminone from one-pot five-component reactions under catalyst free conditions.

Base-promoted intramolecular cyclization of N-alkyl, N-propargylic β-enaminones for the synthesis of polysubstituted pyrroles

An efficient, mild, metal-free, base-mediated intramolecular cyclization of N-alkyl, N-propargylic β-enaminones has been realized for the generation of polysubstituted pyrrole derivatives.

ChemInform Abstract: Synthesis of Polysubstituted Pyrroles Derivatives by PPh3‐Promoted Condensation Reaction Between Ninhydrin, 2‐Amino Pyridine Derivatives and Acetylenes.

AbstractThe one‐pot, three‐component intermolecular Wittig reaction furnishes polysubstituted pyrroles from readily available starting materials under mild conditions without the use of a base or an acid.

Catalytic formal [2+2+1] synthesis of pyrroles from alkynes and diazenes via Ti(II)/Ti(IV) redox catalysis.

Pyrroles are structurally important heterocycles. However, the synthesis of polysubstituted pyrroles is often challenging. Here, we report a multicomponent, Ti-catalysed formal [2+2+1] reaction of alkynes and diazenes for the oxidative synthesis of penta- and trisubstituted pyrroles: a nitrenoid analogue to classical Pauson-Khand-type syntheses of cyclopentenones. Given the scarcity of early transition-metal redox catalysis, preliminary mechanistic studies are presented. Initial stoichiometric and kinetic studies indicate that the mechanism of this reaction proceeds through a formally Ti(II)/Ti(IV) redox catalytic cycle, in which an azatitanacyclobutene intermediate, resulting from [2+2] alkyne + Ti imido coupling, undergoes a second alkyne insertion followed by reductive elimination to yield pyrrole and a Ti(II) species. The key component for catalytic turnover is the reoxidation of the Ti(II) species to a Ti(IV) imido via the disproportionation of an η(2)-diazene-Ti(II) complex.

ChemInform Abstract: Synthesis of Polysubstituted Pyrroles from Activated Alkynes and N‐Propargylamines Through Base‐Catalyzed Cascade Reaction.

AbstractThe K3PO4‐catalyzed cascade Michael addition/alkyne carbocyclization of acetylenedicarboxylate or propargylic ester and propargylamines is developed to synthesize tri‐, tetra‐, and fully substituted pyrroles.

Solvent-free synthesis of polysubstituted pyrroles catalyzed by ZnO nanorods

An efficient zinc oxide nanorod-catalyzed one-pot strategy has been developed for the synthesis of polysubstituted pyrroles in very good yields. The present approach provides a three-component reaction between primary alkylamines, dialkyl acetylenedicarboxylates, and 2-chloro-1,3-dicarbonyl compounds with several advantages such as short reaction time, high yields, solvent free, and little catalyst loading. After reaction course, ZnO nanorods can be recycled and reused without any apparent loss of activity which makes this process cost effective and hence eco-friendly.