Polycyclic Pyrrole Research Articles

Enantioselective synthesis of polycyclic pyrrole derivatives by iridium-catalyzed asymmetric allylic dearomatization and ring-expansive migration reactions

Herein, we report an N-alkylation of pyrroles triggered by an unprecedented selective ring-expansive migration of the spiro-2H-pyrrole intermediates obtained via Ir-catalyzed asymmetric allylic dearomatization. The reaction affords a series of tetrahydropyrrolo[1,2-c]pyrimidine derivatives in good yields (up to 88%) with excellent enantioselectivity (up to >99% ee). The proposed reaction mechanism is supported by DFT calculations and the characterization of the key intermediate.

The Rapid Synthesis of π-Extended Azacorannulenes

In this account we describe our recent development of rapid syntheses of π-extended azacorannulenes. The key to successful synthesis is the use of polycyclic aromatic azomethine ylides, which exhibit extremely high reactivity in sequential 1,3-dipolar cycloadditions with alkenes and alkynes followed by oxidation to form fused pyrroles. This efficient construction of the polycyclic pyrrole structure has led to the rapid synthesis of various π-extended azacorannulenes, which are characterized by their extended π-surface and highly curved, bowl-shaped structures. The present study provides useful insights toward the bottom-up synthesis and property elucidation of heteroatom-containing fullerenes and their fragment molecules.

Polygodial: A viable natural product scaffold for the rapid synthesis of novel polycyclic pyrrole and pyrrolidine derivatives

The dialdehyde polygodial was utilised as a chiral scaffold for the unified synthesis of novel polycyclic pyrrole and pyrrolidine derivatives. Mechanistic insight into the reaction of primary amines with this dialdehyde was obtained. In addition, one of these polycyclic pyrroles was transformed further to prepare novel pentacyclic frameworks.

Intramolecular macrolactonization, photophysical and biological studies of new class of polycyclic pyrrole derivatives.

Herein, we report an efficient synthesis of N-substituted pyrrole derivatives and their application to construct macrocyclic oxazocinone via a two-component coupling reaction followed by base mediated intramolecular cyclization. This methodology provides an easy two-step approach to constitute a library of fused pyrrolo-oxazocinone derivatives in good yields under mild reaction conditions. The present methodology offers an easy access to the synthesis of a library of fluorescent pyrole derivatives. Among them, tert-butyl 2-(2-(3-hydroxypropyl)-7-methoxy-4,5-dihydro-2H-benzo[e]isoindol-1-yl)acetate has been employed in bio-analytical imaging which shows efficient cellular internalization along with no obvious cellular toxicity.

ChemInform Abstract: Enantioselective Synthesis of Pyrrole‐Based Spiro‐ and Polycyclic Derivatives by Iridium‐Catalyzed Asymmetric Allylic Dearomatization and Controllable Migration Reactions.

The first highly diastereo- and enantioselective synthesis of five-membered spiro-2H-pyrroles was achieved using an Ir-catalyzed asymmetric allylic dearomatization reaction. The spiro-2H-pyrrole derivatives readily undergo a controllable and stereospecific allylic migration under acid catalysis, providing polycyclic pyrrole derivatives in excellent yields and ee values. Additionally, the novel Ir-complex K1, derived from [Ir(cod)Cl]2 (cod=1,5-cyclooctadiene) and N-benzhydryl-N-phenyldinaphthophosphoramidite (BHPphos), showed excellent control of both diastereo- and enantioselectivities.

Enantioselective Synthesis of Pyrrole-Based Spiro- and Polycyclic Derivatives by Iridium-Catalyzed Asymmetric Allylic Dearomatization and Controllable Migration Reactions.

The first highly diastereo- and enantioselective synthesis of five-membered spiro-2H-pyrroles was achieved using an Ir-catalyzed asymmetric allylic dearomatization reaction. The spiro-2H-pyrrole derivatives readily undergo a controllable and stereospecific allylic migration under acid catalysis, providing polycyclic pyrrole derivatives in excellent yields and ee values. Additionally, the novel Ir-complex K1, derived from [Ir(cod)Cl]2 (cod = 1,5-cyclooctadiene) and N-benzhydryl-N-phenyldinaphthophosphoramidite (BHPphos), showed excellent control of both diastereo- and enantioselectivities.

Enantioselective Synthesis of Pyrrole‐Based Spiro‐ and Polycyclic Derivatives by Iridium‐Catalyzed Asymmetric Allylic Dearomatization and Controllable Migration Reactions

AbstractThe first highly diastereo‐ and enantioselective synthesis of five‐membered spiro‐2H‐pyrroles was achieved using an Ir‐catalyzed asymmetric allylic dearomatization reaction. The spiro‐2H‐pyrrole derivatives readily undergo a controllable and stereospecific allylic migration under acid catalysis, providing polycyclic pyrrole derivatives in excellent yields and ee values. Additionally, the novel Ir‐complex K1, derived from [Ir(cod)Cl]2 (cod=1,5‐cyclooctadiene) and N‐benzhydryl‐N‐phenyldinaphthophosphoramidite (BHPphos), showed excellent control of both diastereo‐ and enantioselectivities.

Benzimidazole Annulated New Heterocyclic Compounds: Synthesis of Polycyclic Pyrrole Derivatives

Several (3) new benzimidazole based polycyclic compounds of potential pharmaceutical interest have been prepared starting from 2-benzimidazolelyl (1,3-dioxo-2-indenylidene) acetonitrile. Unhypothesized, the C≡N function of the plausible intermediates was released as HCN rather than a classical nucleophilic addition when treated with bidentate reagents such as hydrazines, 5-amino-1H-1,2,4-triazole, 5-amino-4-cyano-1H-pyrazole and 2-aminobenzimidazole. When compound 3 reacted with active acetonitrile derivatives it afforded new polyfunctional pyridines via elimination of HCN in addition to, new pyrimidine, pyrazine and azepine derivatives.

Naphthobipyrrole: Versatile Synthesis and Electropolymerization

A facile synthetic route to a new polycyclic pyrrole derivative, 3,8-diethyl-1,10-dihydro-benzo[e]pyrrolo[3,2-g]indole (1), is reported. This annulated bipyrrole acts as a monomer for electropolymerization and forms an electrochromic conducting polymer (poly1) when electrooxidized at low potentials (0.4 V vs Ag/Ag(+)) in acetonitrile. The presence of alkyl substituents at the 3 and 8 carbons (β-pyrrolic positions) induces regioselective 2,5'-coupling of the pyrrole repeat units and gives rise to the more uniform polymeric product, poly1. Poly1 exhibits globular morphology, as judged from SEM pictures. Its spectroelectrochemical features can be attributed to the formation of four possible states: neutral, polaron, bipolaron, and transverse bipolaron. The relatively low switching potentials (-0.6 to +0.9 V vs Ag/Ag(+) in MeCN) displayed by poly1 leads us to suggest that 1 has a role to play as a polymerizable moiety for the development of multicolor electrochromic materials.

ChemInform Abstract: Palladium‐Catalyzed Sequential Reactions via Allene Intermediates for the Rapid Synthesis of Fused Polycyclic Pyrrole Derivatives.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 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: Single and Consecutive Cyclization Reactions of Alkynyl Carbene Complexes and 8‐Azaheptafulvenes: Direct Access to Polycyclic Pyrrole and Indole Derivatives.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 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.

Palladium‐Catalyzed Sequential Reactions via Allene Intermediates for the Rapid Synthesis of Fused Polycyclic Pyrrole Derivatives

AbstractIn this paper, we report a novel sequential reaction sequence consisting of a series of processes including Sonogashira coupling, propargyl‐allenyl isomerization, [3+2] cycloaddition, denitrogenation, and highly selective biradical coupling reaction, providing an efficient synthesis of fused polycyclic pyrrole derivatives. The reaction features one CC bond and two CN bonds formed to construct the pyrrole unit, together with two rings efficiently assembled in one stroke.

Single and Consecutive Cyclization Reactions of Alkynyl Carbene Complexes and 8‐Azaheptafulvenes: Direct Access to Polycyclic Pyrrole and Indole Derivatives

The reactivity of alkynyl and enynyl Fischer carbene complexes towards 8-azaheptafulvenes is examined. Alkynyl carbenes 1 a-f undergo regioselective [8+2] heterocyclization with 8-aryl-8-azaheptafulvenes 2 a, b providing cycloheptapyrroles 3 and 4 with metal carbene or ester functionality at C3. Moreover, consecutive cyclization reactions are involved when enynyl carbenes are used. Thus, the cyclopenta[b]pyrrole framework 7 is formed by the consecutive [8+2] cyclization and cyclopentannulation reactions. The initially formed cyclopentannulation adduct can be intercepted through a Diels-Alder reaction with classic dienophiles to afford increasing structural complexity (compounds 8 and 9). More importantly, the construction of the indole skeleton is accomplished with a high degree of substitution and functionalization (compounds 11-15) by a one-pot sequence that involves [8+2] cyclization, R--NC or CO insertion, and ring closure.

Eight‐Step Synthesis of Routiennocin

AbstractRoutiennocin is a member of a family of polycyclic pyrrole ether antibiotics that simultaneously uncouple oxidative phosphorylation and inhibit ATPase as a result of selective complexation of divalent metal ions. We describe a concise synthesis of routiennocin with the longest linear sequence of 8 steps. Our synthesis features a unique bi‐directional strategy, which entails a sequential ring‐opening/cross metathesis of a highly strained cyclopropenone acetal. This approach enables rapid and highly convergent assembly of the fully extended polyketide subunit of this natural product from readily available homoallylic alcohol precursors.

ChemInform Abstract: Multi‐Component Coupling Synthesis of Polycyclic Pyrrole Derivatives via Ir‐ and Rh‐Catalyzed Cycloisomerizations with Microwave Heating.

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.

Multi-component coupling synthesis of polycyclic pyrrole derivatives via Ir- and Rh-catalyzed cycloisomerizations with microwave heating

CuBr 2-catalyzed three-component coupling of N-benzylallylamine, ethyl glyoxalate, and terminal alkynes afforded glycinate-tethered 1,6-enynes, which were further transformed into polycyclic pyrrole-2-carboxylates via iridium-catalyzed cycloisomerization/Diels–Alder cycloaddition/dehydrogenation sequence under conventional and microwave heating conditions. The corresponding β-amino acid analogues were obtained from the Ir-catalyzed reaction of enynes prepared from lithium amides of allylamines with methyl non-2-en-4-ynoate. The Cu-catalyzed Mannich-type condensation was further extended to the synthesis of the glycinate-tethered dienyne and cyclopropylenyne, which were subjected to Rh-catalyzed cycloisomerizations to furnish bicyclic amino acids.

A New Method for the Synthesis of Plurisubstituted Pyrroles.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Rhodium‐Catalyzed Cyclopropanation Using Ene‐yne‐imino Ether Compounds as Precursors of (2‐Pyrrolyl)carbenoids.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A new method for the synthesis of plurisubstituted pyrroles

A versatile method for the synthesis of pyrroles is described using an intramolecular [3+2] cycloaddition reaction. This method allows the expedient preparation of ‘plurisubstituted’ compounds in which functionality is incorporated by choice, using appropriate readily available starting materials. Polycyclic pyrrole derivatives as well as 2-aryl monocyclic analogues are described. Several families of compounds are synthesized by sequential transformations. The method is designed to allow the creation of libraries with increased diversity of functionality by combinatorial or parallel synthesis.

Rhodium-catalyzed cyclopropanation using ene-yne-imino ether compounds as precursors of (2-pyrrolyl)carbenoids.

[reaction: see text] The reaction of alkenes with conjugated ene-yne-imino ether or ene-yne-aldimine in the presence of a catalytic amount of [Rh(OAc)(2)](2) gives (2-pyrrolyl)cyclopropanes in good yields. The key intermediate of this cyclopropanation is a (2-pyrrolyl)carbenoid generated by the nucleophilic attack of imine nitrogen atom at an internal alkyne carbon activated by rhodium complex. The intramolecular reaction also proceeds to afford a polycyclic pyrrole.