Pyrroles 1.2- diaryl

Pyrrole, 3,4-dialkyl-2-ethyl-5-methyl-benzoylation, 4, 220 Pyrrole, 1,2-diamino-reactions, 4, 300 Pyrrole, 2,5-diamino-tautomerism, 4, 200, 299 Pyrrole, 2,4-diaryl-nitration, 4, 210 Pyrrole, 2,5-diaryl-synthesis, 4, 343 Pyrrole, 3,4-diaryl-synthesis, 4, 343 Pyrrole, di-t-butyl-protonation, 4, 47 Pyrrole, 2,5-dichloro-synthesis, 4, 368... 

Other PK variations include microwave conditions, solid-phase synthesis, and the fixation of atmospheric nitrogen as the nitrogen source (27—>28). Hexamethyldisilazane (HMDS) is also an excellent ammonia equivalent in the PK synthesis. For example, 2,5-hexanedione and HMDS on alumina gives 2,5-dimethylpyrrole in 81% yield at room temperature. Ammonium formate can be used as a nitrogen source in the PK synthesis of pyrroles from l,4-diaryl-2-butene-l,4-diones under Pd-catalyzed transfer hydrogenation conditions. 

In the frame of a medicinal project at J J Pharmaceutical Research and Development aimed at designing new potent and selective glycogen synthase kinase-3/i (GSK-3/3) inhibitors, the C-3 derivatization of the 1-methyl-4-[l-alkyl-lff-indol-3-yl]-lff-pyrrole-2,5-dione scaffold was explored [31]. Microwave-assisted Stille reaction of 3-chloro-l-methyl-4-[l-alkyl-lff-indol-3-yl]-lH-pyrrole-2,5-diones with (2,4-dimethoxy-5-pyrimidinyl)(tributyl) stannane at 200 °C yielded in 6 min the desired 3,4-diaryl-lff-pyrrole-2,5-diones in moderate yields (Scheme 12). 

Stated to be particularly useful in the treatment of obesity, a series of 1,5-diaryl-pyrrole-based compounds from AstraZeneca was claimed in a recent patent application [313], including compound (509). Although no specific biological data were presented, the CBi receptor affinities are claimed to be less than 1 pM and preferably less than 200 nM. 

Furo[3,4-c]pyrrolediones are important intermediates in the synthesis of diketo-pyrrolopyrrole (DPP) pigments. Smith and coworkers have described the preparation of several different 3,6-diaryl-substituted furo[3,4-c]pyrrole-l,4-diones by microwave-assisted cyclization of readily available 4-aroyl-4,5-dihydro-5-oxo-2-arylpyrrole-3-carboxylates (Scheme 6.192) [353]. While conventional heating in Dowtherm A at 230-240 °C for 64 h provided only moderate product yields, microwave irradiation of the neat starting material at 250 °C for 10 min provided significantly increased yields. 

Katritzky developed a facile synthesis of l,2-diaryl(heteroaryl)pyrroles in a two-step procedure from A-allylbenzotriazoles via intramolecular oxidative cyclization in the presence of a Pd(II) catalyst <00JOC8074>. Thus, treating A-allylbenzotriazole (21) with n-butyllithium followed by addition of a diarylimine yielded the (2-benzotriazolyl-l-arylbut-3-en)anilines 22 which were subsequently heated in the presence of the system Pd(OAc)2-PPh3-CUCI2-K2CO3 to undergo intermolecular amination with simultaneous oxidation of the intermediate 3-pyrroline to the pyrroles 23. 

Petrillo reports that the reaction of l,4-diaryl-2,3-dinitrobutadienes 42 with representative primary amines leads to //-alkyl-3-alkylamino-2,5-diaryl-4-nitropyrrolidines 43 presumably via a disfavored 5-endo-trig ring closure <00EJOC903>. Acid catalyzed elimination of the amine led to the corresponding trans-2,5-diaryl-3-nitro-3-pyrrolines 44 which could be dehydrogenated to the corresponding pyrroles 45. 

Alder/retrograde Diels-Alder reaction sequence of a diaryl alkyne with a 3,6-dicarbomethoxy tetrazine. The resulting diazine (14) is then reduced, cleaved and cyclized with Zn/acetic acid to the 2,3,4,5-tetrasubstituted pyrrole (15), which is then N-alkylated with a-bromo-4-methoxyacetophenone to give a pentasubstituted pyrrole (16). The synthesis of lukianol A is completed by ester hydrolysis, decarboxylation, ring closure and deprotection. 

Lycogalic acid (131) and halitulin (132) represent unique analogs (Fig. 8) to the 3,4-diaryl pyrrole scaffold of the natural products previously discussed. Lycogalic acid (131) contains indole rings attached at both C-3 and C-4 of... 

Using 2-bromopyrrole 72, Burgess has synthesized 2-arylpyrroles 73 in excellent yield [61], The resulting hydrolyzed pyrroles 74 were used to prepare 3,5-diaryl BODIPY dyes. 

Boger has reported efficient total syntheses of the marine alkaloids ningalin A, lamellarin O, lukianol A, and stomiamide A each of which possess a common 3,4-diaryl-substituted pyrrole nucleus bearing 2- or 2,5-carboxylates <99JA54>. A key step in each of these syntheses utilized a zinc mediated reductive ring contraction of 1,2-diazines such as 29 to pyrrole 30, a precursor in... 

Anodic oxidation of l,3-diaryl-5-methyl-A2-pyrazoline-5-carboxylic acids in CH3CN-Et4NBF4 proceeded with decarboxylation to the aromatized pyrazoles in high yield.414 Similarly, electrochemical oxidation of N-acetyl-2,3-substituted A4-pyrroline-2-carboxylic acids in water-tetrahydrofuran (3 1) containing KOH forms the corresponding pyrroles (80-98%).415... 

Predictably, nitrosation of 2-acetylpyrrole and pyrrole-2-carboxylic esters with alkyl nitrites or nitrous acid preferentially yields the relatively stable 4-nitroso derivatives, whilst 2,4-dialkyl- or -diaryl-pyrroles are nitrosated at the 5-position. Further reaction of the dialkyl and diaryl nitrosopyrroles with an excess of alkyl nitrite in the absence of a base can result in the formation of the nitropyrroles, whereas the reaction with nitrous acid converts the nitrosopyrroles into diazopyrroles (B-77MI30502). 

Pyrrole- and indole-carboxylic acid chlorides react with dialkyl- and diaryl-cadmium to yield the ketones and it is noteworthy that the reaction of the anhydride of indole-2,3-dicarboxylic acid with diphenylcadmium produces 3-benzoylindole-2-carboxylic acid and not its isomer (53JCS1889). The ability of l-methylindole-2-carboxylic acid to react with nucleophiles is enhanced by conversion into the mixed anhydride with methanesulfonic acid. The mixed anhydride reacts with carbanions derived from diethyl malonate and from methyl acetate to yield the indolyl (3- keto esters (80TL1957). 

Similar reaction conditions as those by Bose were used for a range of other applications, for example, the synthesis of heterocycles. A combination of a microwave-assisted Paal-Knorr reaction15 with a transfer hydrogenation takes place in the preparation of 2,5-di- and 1,2,5-trisubstituted pyrroles from -l,4-diaryl-2-butene-l,4-diones in a one-pot operation. Hydrogenation was achieved with ammonium formates and 10% Pd/C as catalyst in PEG-200. Yields of up to 92% were obtained within 0.5-2 min (Scheme 4.2)16. 

Rao, H.S.P. and Jothilingam, S., One-pot synthesis of pyrrole derivatives from ( )-1,4-diaryl-2-butene-1,4-diones, Tetrahedron Lett., 2001, 42, 6595-6597. 

Sanchez-Garcia (09OL77) has reported a one-pot procedure (Scheme 21) for the synthesis of 4,4 -diaryl-4,4 -diheteroaryl-substituted-2,2 -bipyrrole 45 based on the oxidative coupling of 2-trimethylstannylated pyrrole 44. 

Katritzky and coworkers have developed two new methods of pyrrole synthesis involving condensation of C3-C4-C5 synthons with Schiff bases to obtain 1,2-diaryl pyrroles. The synthon 2a is obtained by condensation of acrolein, morpholine and benzotriazole, followed by a base-catalyzed elimination. Lithiation gives an anion which adds to the imine. Cyclization occurs on acid treatment. <95TL343> An alternative synthon is obtained by lithiation of 2b. <95S1315>... 

Aryl- or 3,4-diaryl pyrroles 1 can be conveniently prepared in moderate to good yields from the readily available arylalkenes 2 and TosMIC in the presence of base in a one step operation <02OL3537>. 3,4-Disubstituted pyrroles have also been obtained by the action of TosMIC on various 2-tropanones in the presence of sodium ethoxide <02JOC5019>. 

Carbonsulfur bonds can be formed by the reaction of elemental sulfur with a lithio derivative, as illustrated by the preparation of thiophene-2-thiol 446. If dialkyl or diaryl disulfides are used as reagents to introduce sulfur, then alkyl or aryl sulfides are formed sulfinic acids are available by reaction of lithium derivatives with sulfur dioxide. In the pyrrole series, a 2-thiol and the corresponding selenol can be prepared via reaction of 2-lithio-l-methylpyrrole with sulfur or selenium, then trapping with Me3SiCl leading to the 2-Me3SiX-substituted derivatives <1997T13079>. 

A comparison of the absorption and fluorescence properties of 3,5-diaryl-l//-pyrrole-2-carboxylic acid ethyl esters reveals marked effects of/i-dimethylamino and o-methyl substituents on the phenyl group at C-3 and suggests that in the presence of these substituents emission occurs either from a charge transfer state or from a combination of charge transfer and locally excited states <2005NJC1258>. 

Reactions of dialkyl or diaryl chlorophosphines with pyrroles 274 give l-(phosphino)-l//-pyrroles 275... 

A synthesis of a set of 2-pyridylpyrroles has been described, involving annulation of 1,3-dicarbonyl compounds with 2-(aminomethyl)pyridine under acidic conditions, as illustrated by the construction of compound 437 (Equation 121) <20020L435>. Likewise, pyrroles have also been obtained from reactions between 1,3-diaryl-l,3-dicarbonyl compounds and imines or oximes promoted by the TiCU/Zn-system <2004SL2239>. Yet another approach involves rhodium-catalyzed reactions of isonitriles with 1,3-dicarbonyl synthons, which enables for instance preparation of fluorinated pyrroles <20010L421>. 

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