Amines pyrrole ring

The oxidation of poly(N-phenyl-3,4-dimethylenepyrroline) with DDQ or Pd/C in nitrobenzene gave in a cyclic aromatic amine polymer with repeating pyrrole rings in the polymer backbone. Using Pd/C in... 

Pyrrole is one of the most prominent heterocycles, having been known for more than 150 years, and it is the structural skeleton of several natural products, synthetic pharmaceuticals, and electrically conducting materials. A simple access to the pyrrole ring system involves the conversion of cyclic anhydrides into five-membered imides. Mortoni and coworkers have described the conversion of 2-methylquinoline-3,4-dicarboxylic acid anhydride to a quinoline-3,4-dicarboximide library by treatment of the anhydride with a diverse set of primary amines under microwave conditions (Scheme 6.180) [341]. The authors studied a range of different conditions, including dry media protocols (see Section 4.1) whereby the starting materials were adsorbed onto an inorganic support and then irradiated with microwaves. For the transforma-... 

Another method for preparing pyrrole rings is by Ugi-type three-component condensation (Scheme 6.184). In the protocol published by Tye and Whittaker [345], levulinic acid was reacted with two different isonitriles and four amine building blocks (1.5 equivalents) to provide a set of eight pyrrole derivatives. While the previously published protocol at room temperature required a reaction time of up to 48 h and provided only moderate product yields, the microwave method (100 °C, 30 min) optimized by a Design of Experiments (DoE) approach (see Section 5.3.4), led to high yields of the desired lactams for most of the examples studied. 

While the Mori-Ban indole synthesis is catalyzed by a Pd(0) species, the Hegedus indole synthesis is catalyzed by a Pd(II) complex. In addition, the Mori-Ban indole synthesis is accomplished via a Pd-catalyzed vinylation (a Heck recation), whereas the Hegedus indole synthesis established the pyrrole ring via a Pd(II)-catalyzed amination (a Wacker-type process). Hegedus conducted the Pd-induced amination of alkenes [430] to an intramolecular version leading to indoles from o-allylanilines and o-vinylanilines [291-293, 295, 250, 251]. Three of the original examples from the work of Hegedus are shown below. 

The linear tetrapyrrole has methylene bridges between the pyrrole rings we start from porphobilinogen that has either -H or -CH2NH2 as the ring substituents at these positions. Since the nitrogens are lost, we should consider an elimination, and this is assisted by the pyrrole nitrogen. We can consider protonation of the amine to facilitate the elimination. The product is an electrophilic methylidene pyrrolium cation. 

The development of methods to effect nucleophilic addition to carbon-carbon double bonds by prior activation with metal cations has been applied, at least in a preliminary way, as a method of pyrrole ring closure. The conversion of butadienes to N-substituted pyrroles can be accomplished in two stages. In acetic add, 1,4-dienes react with PdnCl2 to give tr-allyl complexes with introduction of acetate at C-4. The ir-allyl complexes then react with amines to give a l-amino-4-acetoxy-2-butene (equation 70). When the addition of the amine is carried out in the presence of a silver salt and triphenylphosphine, a pyrrole is isolated, probably by cyclization of the amino-substituted allyl-Pd complex (equation 71) (81CC59). Although this procedure is attractive in terms of the simplicity of the... 

There are numerous additional studies based on the properties of enam-ines and the synthesis of the pyrrole ring. Thus, fusion of dienetriamines formed by a reaction of aminals of a,/3-unsaturated /3-dimethylaminoalde-hydes (41) with /V-acetylindoxyl results in cyclization to pyrroloindoles (42) (87IZV821). Dienetriamino derivatives of a different type (43) obtained from indoxyl are also transformed into pyrrolo[l, 2-a]indoles (44) upon... 

Another example of reaction-rate enhancement was reported for the microwave-assisted Paal-Knorr synthesis of a series of tetrasubstituted pyrroles [18]. Following the standard procedure, 1,4-dicarbonyl compounds were converted to pyrrole rings via acid-mediated dehydrative cyclization in presence of primary amines. The main limitation of the standard protocol is the harsh reaction conditions (reflux in acetic acid for extended times). The use of microwaves slashes the reaction times to few minutes, giving good isolated yields of the desired products (Scheme 15.5). 

A useful expansion of the pyrrole-ring annelation methodology was found when 3-alkynyl-6,8-dimethylpyrimido[4,5-< ]pyridazine-5,7(6//,8//)-dione reacts with an amine and silver permanganate pyridine complex. It was postulated that first amination at the C4-position takes place, followed by an intramolecular cyclization into the pyrrolopyridazinopyrimidine derivative (Scheme 35). A similar reaction was reported with 6-alkynyl-l,3-dimethylpyrimido[4,5-Z]pyrazinedione (03MI3). 

The pyrrole ring may also be approached via Fischer-type indolizations. Thus the amine (159) was elaborated to the pyruvate hydrazone (160) which by Fischer procedures gave the benzodipyrrole (161) <79ABC555, 79ABC559). 

The Nal/TMSCl/EtsN-mediated condensation between 2-(pyrrol-Tyl)benzaldehydes 486 and secondary amine hydrochlorides followed by intramolecular trapping of the resulting iminium carbon by the 2-position of the pyrrole ring 487 afforded corresponding 977-pyrrolo[l,2- ]indoles 488 generally in good yields (Scheme 100) <2006T3158>. 

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