Bicyclic Pyrroles Research Articles

The [3 + 2] Cycloaddition Reaction of N-Substituted Pyrrole-2-carboxaldehydes with Arylalkenes under Copper Catalysis: Access to Dihydropyrrolizine Skeletons.

Herein, we found that treating N-substituted pyrrole-2-carboxaldehydes with arylalkenes in DMF in N2 at 120 °C could afford pyrrolidine scaffolds with an up to 85% yield. This approach has several remarkable features, such as atom and step economy, readily accessible raw materials, and easy-to-operate manner, providing a simple and efficient method for constructing complicated bicyclic pyrroles. Additionally, we have successfully synthesized 28 target compounds, which further demonstrates its practicality and wide applicability.

Divergent Cyclizative Approaches of In Situ Formed β-Keto-Allenes: Chemo- and Regioselective Synthesis of Bicyclic Furans, and Pyrroles

A unified strategy for the construction of bicyclic furans and pyrroles is developed from tert-propargyl alcohols and α-acyl cyclic ketones using an alkaline earth catalyst under solvent-free conditions. The reaction proceeds via the formation of a β-keto allene intermediate, which upon treatment with a tert-amine underwent thermodynamic enol formation and a subsequent annulation to form bicyclic furans. Interestingly, the same allene forms bicyclic pyrrole with primary amines. The reaction shows excellent atom economy as water is the only byproduct formed in bicyclic furans. The generality of the reaction is well established. Gram-scale synthesis and synthetic applications are demonstrated.

Azomethine ylide cycloaddition of 2-C-formyl glycals with α-amino acids for the synthesis of substituted pyrroles

A novel strategy has been devised for the synthesis of pyrrole based acyclo-C-nucleosides, in particular an open-chain sugar substituted pyrrole derivatives by means of the condensation of 2-C-formyl glycals with α-amino acids through an intramolecular azomethine cycloaddition under thermal conditions. The use of cyclic α-amino acids provides the corresponding bicyclic pyrrole derivatives. This is a first report on the synthesis of pyrrole based acyclo-C-nucleosides. 2009 Elsevier Ltd. All rights reserved.

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines.

A one-flask, two-step procedure from 3-amino-2-methyl-5,6,7,7a-tetrahydro-1H-pyrrolizin-1-one affords the Streptomyces secondary metabolites legonmycins A and B – three operations overall from methyl N-Boc-prolinate. The key step proceeds in each case via N,O-diacylation, then selective oxidative hydrolysis of the intermediate bicyclic pyrrole and establishes a precedent for the synthesis of related C(7a)-hydroxylated pyrrolizidines.

The Castagnoli–Cushman reaction of bicyclic pyrrole dicarboxylic anhydrides bearing electron-withdrawing substituents

Four anhydrides of 1-(carboxymethyl)pyrrole-2-carboxylic acids bearing electron-withdrawing substituents at positions 6 or 7 of the bicyclic system have been investigated in the Castagnoli–Cushman reaction with imines. 6-Benzoyl- and 7-sulfamoyl-substituted anhydrides demonstrated lower reactivity while 7-benzoyl derivative displayed broader substrate scope. These findings have been rationalized from the mechanistic perspective.

Synthesis of trifluoromethyl and trifluoroacetyl substituted dihydropyrrolizines and tetrahydroindolizines

The trifluoroacetic anhydride promoted cyclization of enaminones derived from proline or pipecolic acid and β-ethoxyvinyl trifluoromethyl ketone was reinvestigated. An operationally simple procedure for the selective synthesis of bicyclic trifluoromethylated pyrroles and bicyclic pyrroles bearing trifluoromethyl and trifluoroacetyl groups on the pyrrole ring was developed. The mechanism of cyclization explaining the formation of bicyclic trifluoromethylpyrroles was discussed and previously described structures of the cyclization products were corrected.

Cascade Reaction of Morita-Baylis-Hillman Acetates with 1,1-Enediamines or Heterocyclic Ketene Aminals: Synthesis of Highly Functionalized 2-Aminopyrroles.

A new strategy for the construction of two kinds of fully substituted pyrroles, including 2-aminopyrroles and bicyclic pyrroles from Morita-Baylis-Hillman (MBH) acetates with 1,1-enediamines (EDAMs), or heterocyclic ketene aminals (HKAs) via base-promoted tandem Michael addition, elimination, and aromatization sequence has been developed, affording the expected products in moderate to excellent yields. This methodology is a highly efficient, concise way to access 2-aminopyrroles or bicyclic pyrroles with diversity in molecular structures from accessible building blocks under moderate reaction conditions.

Simple Synthesis of Bicyclic Pyrrole Ketone Compounds

In this article, a one-pot protocol was established for the synthesis of bicyclic pyrrole ketone compounds. This method based on the building blocks of heterocyclic ketene aminals 1, which reacted with oxalaldehyde 2 in 1,4-dioxane at 50 ℃ and triethylamine as base. As a result, a series of bicyclic pyrrole ketone compounds 3a~3i have been synthesized. This reaction has some advantages such as simple synthetic route, readily available starting materials, high yields and simple work-up procedures.

ChemInform Abstract: Palladium(II)‐Catalyzed Cyclization of Heterocyclic Ketene Aminals with (E)‐Ethyl 2,3‐Diiodoacrylates: Selective Synthesis of Bicyclic Pyrroles and Bicyclic Pyridones.

Abstract A concise and efficient synthesis of novel bicyclic pyrroles has been achieved by PdCl2-catalyzed cyclic condensation of six-membered heterocyclic ketene aminals (HKAs) or seven-membered HKAs with ethyl 2,3-diiodoacrylate and diethyl 2,3-diiodofumarate in the presence of Cs2CO3, respectively. A series of novel bicyclic pyridones have also been obtained via five-membered HKAs with diethyl 2,3-diiodofumarate under the optimized conditions in moderate yields. These reactions are the first application of a transition metal to catalyze the building blocks HKAs to form the bicyclic pyrrole library via condensation reaction.

ChemInform Abstract: Three‐Component Domino Reaction Synthesis of Highly Functionalized Bicyclic Pyrrole Derivatives.

AbstractFully substituted highly functionalized pyrroles (IV) are synthesized by an acetic acid catalyzed three‐component domino reaction of cyclic ketene aminals (I), arylglyoxal hydrates (II), and indoles (III).

Palladium(II)-catalyzed cyclization of heterocyclic ketene aminals with (E)-ethyl 2,3-diiodoacrylates: selective synthesis of bicyclic pyrroles and bicyclic pyridones

A concise and efficient synthesis of novel bicyclic pyrroles has been achieved by PdCl2-catalyzed cyclic condensation of six-membered heterocyclic ketene aminals (HKAs) or seven-membered HKAs with ethyl 2,3-diiodoacrylate and diethyl 2,3-diiodofumarate in the presence of Cs2CO3, respectively. A series of novel bicyclic pyridones have also been obtained via five-membered HKAs with diethyl 2,3-diiodofumarate under the optimized conditions in moderate yields. These reactions are the first application of a transition metal to catalyze the building blocks HKAs to form the bicyclic pyrrole library via condensation reaction.

Three-component domino reaction synthesis of highly functionalized bicyclic pyrrole derivatives

An efficient one-pot synthesis of highly functionalized bicyclic pyrrole derivatives by a three-component domino reaction of heterocyclic ketene aminals (HKAs), arylglyoxal monohydrate, and indoles in ethanol medium catalyzed by acetic acid is described. In this procedure, three sigma bonds were formed simultaneously. The present synthesis features excellent regio-selectivity, easy purification as well as simple starting materials.

ChemInform Abstract: Formation of Bicyclic Pyrroles from the Catalytic Coupling Reaction of 2,5‐Disubstituted Pyrroles with Terminal Alkynes, Involving the Activation of Multiple C—H Bonds.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Formation of Bicyclic Pyrroles and Furans Through an Enone Allene Photocycloaddition and Fragmentation Sequence.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Formation of Bicyclic Pyrroles and Furans Through an Enone Allene Photocycloaddition and Fragmentation Sequence

AbstractThe [2+2] photocycloaddition of allenes 15–18, 23 and 26 was studied. Irradiation of a solution of these substrates in acetonitrile at 300 nm resulted in the clean conversion of the starting materials into a mixture of photoproducts. The major product in all cases was a bicyclic pyrrole or furan fused to an eight membered ring (43–70 % yield). The formation of these products is thought to be a result of a heteroatom‐induced fragmentation of the straight adduct (7). This is supported by irradiation of the carbon analogue 32 which allowed the isolation of straight adduct 45 after catalytic hydrogenation in 27 %. The minor crossed photoproducts were isolated in 10–20 % yield. The observed major/minor ratio of 4:1 was not affected by the variation of substituents on the cyclohexene ring. Introduction of a substituent on the allene had a more significant effect on the ratio which changed to 2:1.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Formation of bicyclic pyrroles from the catalytic coupling reaction of 2,5-disubstituted pyrroles with terminal alkynes, involving the activation of multiple C-H bonds.

Substituted bicyclic pyrroles are produced directly from the coupling reaction of 2,5-disubstituted pyrroles with terminal alkynes, involving the activation of multiple C-H bonds and regioselective cyclisation.

5-Methyl-1-(p-tolylsulfonyl)-2,3,4,5-tetrahydrocyclopentene[b]pyrrole

The title compound, C15H19NO2S, is a bicyclic pyrrole derivative synthesized by an intra­molecular C—C coupling reaction. The mol­ecules are connected via weak C—H⋯O inter­actions, forming dimers in the crystal structure.

Synthesis of the aziridinomitosene skeleton by intramolecular Michael addition: alpha-lithioaziridines and nonaromatic substrates.

The bicyclic pyrrole ketone 16 has been prepared by using an oxaza-Claisen rearrangement, followed by nitrogen deprotection. Coupling with the stannylaziridine mesylate 15a or nosylate 15b affords 17. Conversion to 40 provides a substrate for generation of an alpha-lithioaziridine 41 by tin lithium exchange. An intramolecular Michael addition pathway for 41 has been demonstrated by the isolation of 46 in 20% yield under conditions where the intermediate enolate 43 is trapped by selenenylation, but competing proton transfer gives 42. The synthetic potential of the process is limited by stability problems at the stage of the enolate 43 or the protonated product 44.

Synthesis of Pyrrole Derivatives Through Functionalization of 3,4‐Bis(lithiomethyl)dihydropyrroles.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of Pyrrole Derivatives through Functionalization of 3,4‐Bis(lithiomethyl)dihydropyrroles

AbstractBis(2‐lithioallyl)amines 2, substituted at the double bonds, undergo intramolecular carbolithiation of a lithiated double bond in different solvents to afford dilithiated dihydropyrroles 3. Treatment of these dianions with electrophiles allows the preparation of functionalized pyrrole derivatives 5 and 6. Interestingly, treatment of these dianions with carboxylic esters selectively affords either keto or hydroxy compounds (9 or 10), depending on the conditions. Several experiments have been carried out in order to clarify the mechanism of this selective transformation. Finally, dilithiated dihydropyrrole 3a could be transformed in a three‐step procedure into the corresponding 3,4‐bis(bromomethyl) derivative 31, which can easily be converted into bicyclic pyrrole compounds 32−33 by treatment with different nucleophiles. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)