La(OTf)3 catalyzed synthesis of α-aryl tetrasubstituted pyrroles through [4+1] annulation under microwave irradiation

A La(OTf)₃ catalyzed synthesis of tetrasubstituted pyrroles under microwave irradiation has been developed affording various α-aryl tetrasubstituted pyrroles in acceptable to good yields (36–82% yield) through condensation/alkyne azacyclization/isomerization sequence. Functionalized α-aryl pentasubstituted pyrroles could be prepared from tetrasubstituted pyrroles through easy transformations.     

Synthesis of p-Aminophenyl Heteroaromatic Pyrroles

Three general methods for synthesis of heteroaromatic pyrroles were reported recently from our laboratory.¹ Application of these methods to the preparation of p-aminophenyl heteroaromtic pyrroles 3 will be discussed. Potential use of p-aminophenyl substituted heteroaromatic pyrroles 3 as electroluminescent materials is under current investigation.     

Au-catalyzed neighboring hydroxymethyl group directed cycloaddition of alkyne with diazadienes: Synthesis of polysubstituted pyrroles

Polysubstituted pyrroles are very important scaffolds in many bioactive natural products and synthetic pharmaceuticals. Here, a new gold-catalyzed cycloaddition of alkynes with azadienes to access tetrasubstituted pyrroles is demonstrated. The neighboring hydroxylmethyl group serves a very important directing group through an addition/cycloaddition/elimination cascade. Diverse polysubstituted pyrroles were synthesized in good yields under mild conditions in one step, and tricyclic pyrrole containing heterocycles were easily obtained through derivatization.     

A catalyst- and solvent-free three-component reaction for the regioselective one-pot access to polyfunctionalized pyrroles

A facile method for the regioselective synthesis of tetrasubstituted pyrroles, from readily accessible 1,3-dicarbonyls, benzoin derivatives and ammonium acetate, has been developed. The one-pot three-component reactions were performed to afford tetrasubstituted pyrroles under solvent- and catalyst-free conditions.     

Facile,efficient and eco-friendly synthesis of 5-sulfenyl tetrazole derivatives of indoles and pyrroles

A concise, two-step eco-friendly approach towards the synthesis of 5-sulfenyl tetrazole derivatives of indoles and pyrroles, is reported. The synthesis comprises the oxone-mediated thiocyanation of the starting heterocycles towards intermediate 3-thiocyanato indoles and 2-thiocyanato pyrroles, and their subsequent treatment with sodium azide in 2-propanol/water under zinc bromide promotion.     

Copper-catalyzed sulfenylation of pyrroles with disulfides or thiols: directly synthesis of sulfenyl pyrroles

We present here the synthesis of sulfenyl pyrroles by copper-catalyzed sulfenylation of pyrroles with organic disulfides or thiols. The direct sulfenylation of pyrroles with organic disulfides has been accomplished in the presence of 3 mol % of CuI in DMSO at 110 °C under air atmosphere. In the other hand, sulfenylation of pyrroles with thiols were performed in the same solvent and temperature, however it is necessary 5 mol % of CuI and nitrogen atmosphere. Using these protocols we were able to produce 2-sulfenyl pyrroles in good to excellent yields and with high selectivity without use of any ligand or additive.     

Syntheses of calix[4]pyrroles by amberlyst-15 catalyzed cyclocondensations of pyrrole with selected ketones

A facile and efficient protocol is reported for the synthesis of calix[4]pyrroles and N-confused calix[4]pyrroles in moderate to excellent yields by reaction of dialkyl or cycloalkyl ketones with pyrrole catalyzed by reusable Amberlyst(TM)-15 under eco-friendly conditions.     

A facile access to pyrroles from amino acids via an aza-Wacker cyclization

A facile and efficient synthesis of pyrroles from readily available amino acids is described. The key step in the method is an aza-Wacker oxidative cyclization catalyzed by palladium(II)/Cu(OTf)2. A series of pyrroles were obtained by this method under mild conditions.     

Novel thermal iminocyclopropene rearrangements: regioselectivity in the synthesis of pyrroles

A novel and readily available method for synthesis of pyrroles possessing substituents with various functional groups has been developed, by means of thermal iminocyclopropene rearrangements. It will provide a novel and readily available access to pyrroles under mild reaction conditions with simple procedures. The regioselectivity in this iminocyclopropene rearrangement was disclosed.     

Synthesis of polyfunctionalized pyrroles bearing C-2 α-azido side-chains and displacement of the α-azido group by various nucleophiles

Tetrasubstituted pyrroles bearing C-2 α-azido side-chains were synthesized employing a new class of diazides, α,γ-diazido α,β-unsaturated esters, and 1,3-dicarbonyl compounds under simple thermal conditions. Further investigation of the synthetic utility of the obtained pyrroles reveals unexpected displacement of the α-azido group at the C-2 side-chain by a variety of nucleophiles. This two-step process exhibits a broad substrate scope, good functional group tolerance, simple operation, and high reaction efficiency, providing an easy access to polyfunctional pyrroles with novel substitution patterns.     

Synthesis of Iso-condensed Heteroaromatic Pyrroles and Their Application in the Preparation of Conducting Polymers

Iso-condensed heteroaromatic pyrroles 1 are 10 -electron aromatic compounds. They are of interest from both theoretical and synthetic points of view. They are the cyclic analogues of heteroaromatic ortho-quinodimethanes 2, and can react with dienophiles in a Diels-Alder reaction to give the synthetically useful cycloadducts 3. Many of them are also of potential pharmaceutical importance because they are isosteric with indoles. Iso-condensed heteroaromatic pyrroles 1 can be used also as the monomers for the synthesis of new conducting polymers 5 with special properties and characteristics. However, the methods for the efficient preparation of the iso-condensed heteroaromatic pyrroles are quite limited. Iso-condensed heteroaromatic pyrroles are generally unstable in acidic conditions and are easily oxidized by air. In our laboratories, we developed three methods for the preparation of this labile heterocyclic ring system under acidic, neutral, and basic conditions.1 Synthesis of the conjugated systems such as 6 for OLED applications will also be discussed.     

A solvent and transition metal-free,highly efficient Brønsted acidic ionic liquid promoted one-potthree-component reactions for the synthesis of tetrasubstituted pyrroles

Abstract

The present protocol describes a highly efficient, transition metal and solvent-free one-pot annulation of amines, dialkyl acetylenedicarboxylates and β-nitrostyrene using imidazolium Brønsted acidic ionic liquid for the synthesis of tetrasubstituted pyrroles. A diverse functionalized tetrasubstituted pyrroles derivatives were obtained with excellent yields under transition metal and solvent-free conditions. The Brønsted acidic ionic liquid can be easily recovered and reused for the next reaction without any effects on the yields of the products. This green protocol provides structurally complex, medicinally important tetrasubstituted pyrroles with various substitution patterns in a one-pot operation.     

Silver-mediated oxidative C-H/C-H functionalization: a strategy to construct polysubstituted furans

A novel silver-mediated highly selective oxidative C-H/C-H functionalization of 1,3-dicarbonyl compounds with terminal alkynes for the creation of polysubstituted furans and pyrroles in one step has been demonstrated. Promoted by the crucial silver species, perfect selectivity and good to excellent yields could be achieved. This protocol represents an extremely simple and atom-economic way to construct polysubstituted furans and pyrroles from basic starting materials under mild conditions.     

Ethynylation of pyrroles with 1-acyl-2-bromoacetylenes on alumina: a formal ‘inverse Sonogashira coupling’

Pyrroles are cross-coupled with 1-acyl-2-bromoacetylenes on the surface of Al₂O₃ at room temperature under solvent-free conditions to afford 2-(acylethynyl)pyrroles with 100% regioselectivity and in good yields, thus representing the first example of a palladium-, copper-, base-, and solvent-free (‘green’) ethynylation of pyrroles, which can be considered a formal ‘inverse Sonogashira coupling’. Given the interest in functionalized pyrroles and acetylenes, this new facile and environmentally friendly cross-coupling should be of significant interest for the role of acylhaloacetylenes in pyrrole and acetylene chemistry.     

A Two Step Synthesis of 1,2,3-Substituted Pyrroles

A method for preparing substituted pyrroles 3a-g in two steps from dihydrofurans 2a-b which were synthesized from α,α-diazocarbonyl derivatives 1a-b was developed. The relevance of this research work lies in the easiness of preparing the substituted dihydrofurans and transforming them into pyrroles under mild conditions.     

Catalyst-free facile and efficient one-pot synthesis of densely functionalized pyrroles and α-amino ketones

An efficient catalyst-free one-pot three-component synthesis of penta-substituted pyrroles has been successfully developed. A variety of penta-substituted pyrroles were straightforwardly synthesized from good to excellent yields (78%–93%) by using easily accessible starting materials under mild conditions. This protocol also provided α-amino ketones in good yields (87%–98%) without column chromatography.     

Sequential aza-Baylis-Hillman/ring closing metathesis/aromatization as a novel route for the synthesis of substituted pyrroles

A new route to diverse 2-substituted-3-methoxycarbonyl pyrroles has been developed. Diverse SES protected alpha-methylene beta-aminoesters were obtained by a 3-component aza-Baylis-Hillman reaction. Diversity arose from the aryl aldehydes which can be used in this reaction. N-Alkylation with allyl bromide under mild conditions provided the corresponding dienes. These substituted dienes were cyclized by ring closing metathesis at room temperature or under microwave-activation with Grubbs-type II catalyst to yield SES-protected pyrroline intermediates. The final pyrroles were obtained by base-promoted dehydrodesulfinylation/aromatization. The scope of each of these reactions was explored.     

Silica Gel,an Effective Catalyst for the Reaction of Electron-Deficient Nitro-Olefins with Nitrogen Heterocycles

The reaction of electron-deficient olefins with nitrogen heterocycles such as pyrrole and indole was examined in the presence of silica gel at room temperature under stirring at solvent-free conditions. It was found that silica gel is an effective catalyst for this conjugate addition. This work resulted in the formation of monosubstituted pyrroles selectively as a major product except in a few cases where disubstituted pyrroles were also formed as side products. Thus, a simple, rapid, efficient, environmentally benign, and solvent-free method was established.     

Organoaluminum-mediated selective 1,2-rearrangement of γ,γ-disubstituted γ-amino α,β-unsaturated carbonyl compounds leading to unsymmetrically substituted pyrroles

γ,γ-Dialkyl-γ-amino-α,β-unsaturated carbonyl compounds were found to undergo selective skeletal rearrangement under the influence of modified organoaluminum Lewis acid to give unsymmetrically substituted pyrroles through the rapid Paal-Knorr type cyclization upon acidic hydrolysis. This new structural reorganization of amino carbonyl compounds triggered by the 1,2-alkyl shift provides a unique entry to the synthesis of pyrroles, an important class of heterocycles with diverse biological activities.     

Sulfur-based protecting groups for pyrroles and the facile deprotection of 2-(2,4-dinitrobenzene)sulfinyl and sulfonyl pyrroles

[reaction: see text] The effectiveness of simple sulfinyl and sulfonyl groups as electron-withdrawing protecting groups for pyrroles has been analyzed using (13)C NMR spectroscopy and confirmed by consideration of X-ray crystal structures. Additionally, the 2,4-dinitrobenzenesulfinyl and sulfonyl groups are shown to be effective electron-withdrawing protecting groups for pyrroles, and they can be removed by treatment with benzene thiol or thiolate under mild and specific conditions.