Functionalizations pyrrole

Intramolecular nucleophilic additions by nitrogen functional groups onto pendant alkynes and allenes represent an important class of type la approaches to functionalized pyrroles. A platinum-catalyzed (PtCl4) cyclization of homopropargyl azides provided an entry to 2,5-disubstituted pyrroles and 4,5,6,7-tetrahydroindoles (fused pyrroles) <06OL5349>. 

A novel intramolecular photocycloaddition involving vinylogous amides and allenes led to an interesting type lb entry to functionalized pyrroles <060L4031>. For example, photolysis of allene 11 provided fused pyrrole 12 via a [2+2] cycloaddition and retro-Mannich reaction. 

A type Ilac synthesis of functionalized pyrroles was developed that adapted the Larock indole synthesis <06OL5837>. For example, treatment of iodoacrylate 19 and trimethylsilylphenylacetylene 20 with palladium acetate led to the formation of pyrrole-2-carboxylate 21 with excellent regioselectivity. 19 was prepared by iodinating (N-iodosuccinimide) the corresponding commercially available dehydroamino ester. 

A novel ring opening reaction of isoxazoles led to the formation of functionalized pyrroles <06S1021>. For example, treatment of isoxazole 52 with DBU led to the formation of pyrrole 53. A solid-phase synthesis of 3-amino-2,5-dicarboxylates was accomplished by transformation of pyrrol-3-one 54 <06JCC177>. The reaction between 54 and secondary amines led to the corresponding resin-bound aminopyrroles after enamine formation and loss... 

Our own research group [11] has been interested in using vinylogous iminium salt derivatives for the preparation of highly functionalized pyrroles, thereby providing another alternative to the synthesis of lukianol A. 

Diethyl aminomalonate reacts with 1,3-diketones in boiling acetic acid to the corresponding pyrrolecarboxylates 11 (87JOC3986). From N-ac t-amidomalonate and acroleins, pyrrolidines were prepared and they were further transformed into functionalized pyrroles, which are a part of the antibiotic lyncomycin and an antimalarial agent (67JA2459 72JMC1255). 

While dicarboxylic acid-functional pyrroles have received only cursory attention in condensation polymerizations, other derivatives have been studied extensively. Pyrrole itself has been electrooxidatively polymerized (81CS145) to give a flexible conductive film, presumably containing poly(2,5-pyrrolediyl) units (23) as the main structural feature. The blue-black polymer obviously contains other functionality, as evidenced by elemental analysis and by the fact that it carries a partial positive charge, and it exhibits p-type conductivities approaching the metallic range (e.g. 100 fi-1 cm-1). The main utility of poly(pyrrole) (23) has been for the modification of electrode surfaces, although numerous other applications can be envisioned. 

The reaction of cyclohexenamides with nucleophiles such as water, alcohols, or thiols, produced carboxylic acid, esters, or thioesters. Reaction with acetylenic dipolarophiles in acidic conditions produced highly functionalized pyrroles via a complex mechanism, implying as intermediates 1,3-dipoles and bycyclic cycloaddition products. Reaction of cyclohexenamides containing protected hydroxylic functions with AcCl/MeOH produced < -lactones, while cyclohexenamides, bearing in Ri an o-aminophenyl group, easily cyclized to 1, 4-benzodiazepine-2, 5-diones. 

The synthesis and chemistry of pyrroles, indoles, and fused pyrrole and indole compounds reported during the past year (2007) are the subjects of this monograph. Pyrroles and indoles continue to draw a lot of attention from the scientific community due to their prevalence in natural products, diverse biological activity, and materials science applications. Pyrroles and indoles are treated separately. A review article describing the synthesis of highly functionalized pyrroles has appeared <07S3095>. Specialized review articles will be mentioned in the relevant sections. 

Dipolar cycloadditions involving azomethine ylides or munchnones provide access to fused pyrroles and highly functionalized pyrroles. Recent pyrrole syntheses that involve 1,3-dipolar cycloadditions include syntheses of pyrrolo[2,l,5-tfe]quinolizines <07JOC2015>, cy c lo pen ta [ 6 ] py rro le s <07JOC1104>, oligopyrroles <07AG(I)9261>, pyrrolo[2,l-... 

The benzotriazole-functionalized pyrrole derivative 1233 was deprotonated and allowed to react with chalcone to afford a mixture of compounds 1235 and 1236, which without separation was refluxed in 2-propanol/10% H2SO4 to give the corresponding indole 1237 (Scheme 238) <2003JOC5728>. The reaction proceeded through the selective 1,4-addition of lithium derivative 1234 to the enones. Attempts to generalize this methodology with use of ot,)3-unsaturated esters failed. 

Functionalized pyrrolic enols, 2-(2,2-dicyano-l-hydroxyethenyl)-l-methylpyrroles, synthesized from 2-ethenylpyr-roles by a nucleophilic SEt-OH exchange, upon heating (75-142 °C) are readily rearranged to their 3-isomers in near to quantitative yield <2006TL3645>. 

An efficient three-component, one-pot synthesis of functionalized pyrroles, catalyzed by basic ILs in aqueous media, has been described (Fig. 12.29) [21]. 

A three-component, one-pot condensation reaction was described by Yavari and Kowsari [56] by using the [bmim]0H-H20 system to give the functionalized pyrroles in excellent yields. When the benzoyl chlorides, i -phenylalanine, and acety-lenedicarboxylates were allowed to react under an organic alkah catalyst, [bmim] OH-H O provided highly functionalized pyrroles (96% yield) within 15 min (Scheme 17.10). 

Yavari I, Kowsari E (2008) Task-specific basic ionic liquid a reusable and green catalyst for one-pot synthesis of highly functionalized pyrroles in aqueous media. Synlett 897-899... 

A type Ib cyclization involving ketene-iV,S-acetals led to the formation of highly functionalized pyrroles including 4-acetylpyrrole-2-carboxylates <05SC693> and 3,4-diarylpyrroles <05TL475>. The latter are useful building blocks for the preparation of the lamellarin alkaloids. Another approach to the lamellarin framework involved a 1,5-electrocyclization of azomethine ylides <05TL7531>. 

Type Ilbd cyclocondensation reactions between isocyanide-based reagents and electron deficient alkenes or alkynes provides a convenient S3mthetic approach to highly functionalized pyrroles. The cyclocondensation between tosyl methyl isocyanide (TosMic) and 1,2-bis(benzenesulfonyl)ethene provided 3,4-bis(benzenesulfonyl)p)nTole 37 <05JHC333>. 

The electropolymerization of metallocene-functionalized pyrrole and thiophene has been utilized for the creation of organometallic polypyrroles and polythiophenes.181 241 242 243 Zotti et al. reported the electrochemical homo- and copolymerization of ferrocene-functionalized pyrrole, 177.242 Polymer 179 was prepared via the copolymerization of monomer 177 with pyrrole (Scheme 2.48). This polymer possessed an electrical conductivity of 1.5 X 10-2 S/cm. 

The synthesis ofhighly functionalized pyrroles a challenge in regioselectivity and chemical reactivity , 6 ywt/tesis, 2007,3095 Pyrrole. From Dippel to Du Pont , Anderson, H. J., J. Chem. Ed., 1995, 72, 875 The chemistry of pyrroles , Jones, R. A. and Bean, G. R, Academic Press, New York, 1977 Physicochemical properties of pyrroles , Jones, R. A.,Adv. Heterocycl. Chem., 1970,11, 383. 

During the past few years, the polyoxygenated 2,3,4-triarylpyrrole natural products known collectively as the lamellarins have been amongst the most thoroughly studied class of natural products. An interesting cyclocondensation reaction between imine 1 and nitroalkene ester 2 led to highly functionalized pyrrole ester 3, an intermediate which was converted to lamellarin L <04AG(E)866>. A similar reaction with a nitrocoumarin Michael acceptor proved to be less effective. 

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