Arylpyrroles

Two unique type Had syntheses of pyrroles that were reported both involved cyclopropane fragmentations. The first allowed for a synthesis of 2-arylpyrroles <06SL2339>. In the event, treatment of stannylcyclopropane 25 with -BuLi followed by benzonitrile produced 2-phenylpyrrole 26 via tin-lithium exchange, addition to the nitrile, ring fragmentation of ketimine intermediate, intramolecular condensation, and loss of dibenzylamine. 

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. 

The pyrrole-3-boronic acid 67 has been prepared from the 3-iodopyrrole by Muchowski and subjected to a range of Suzuki couplings to afford 2-arylpyrroles 68 [59]. Subsequent fluoride deblocking to give 69 occurs in excellent yield. 

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. 

Condensation of methyl ketones with (3 -dimethylaminonitroethylene gives y-nitro-a,/3-unsaturated enones which can be reductively cyclized to pyrroles. This method was first applied to substituted acetophenones, giving 2-arylpyrroles (equation 84) (74CB1499, 71CB440). 

It was intended (85KGS1501) to find milder synthetic conditions for further simplifying the purification of 3-alkyl-2-phenylpyrroles (5,6) (Scheme 5). It was necessary to increase the DMSO content of the reaction mixture. So, when the synthesis was carried out under pressure in a 10-fold excess (of the total mass of reagents) of DMSO with an equimolar (with respect to ketoxime) amount of KOH, it was possible to decrease considerably the reaction temperature (to 50-60°) and prepare 3-alkyl-2-arylpyrroles (5) and their 1-vinyl derivatives (6) (which more readily undergo purification) in total yield up to 90%. 

The pyrrolization of various alkyl aryl ketoximes (Scheme 6) was also studied [78KGS489 84ZOR1960 90ZOR(ip)], and it was confirmed that the corresponding 2-arylpyrroles (7) could also be obtained successfully in this way (see Table XIII). 

Reaction of aryl methyl ketoximes (118) with vinylchloride in the KOH (5-fold molar excess)/DMSO system at 120°C and atmospheric pressure gave 2-arylpyrroles (119) and their N-vinyl derivatives (120) (Scheme 58) (84KGS1359, 84MI3 87KGS1486). 

In the reaction with 1,2-dichloroethane in KOH/DMSO (100-125°C), aryl methyl ketoximes form 2-arylpyrroles (129) in 70% yield (Scheme 64). The maximum yield of simultaneously formed N-vinylpyrroles (130) and diethers (131) does not exceed 12 and 21%, respectively (86ZOR492). 

The TOSMIC anaiog -(tosyl)benzyl isocyanide readily reacts with simple acceptors (ethyl acrylate, acrylonitrile, etc.) to give 4-substituted 2-arylpyrroles. Extension to 2,3-diaryl derivatives by use of styryl acceptors required the use of n-butyllithium as a base. <95SC795>... 

A general method for the conversion of pyrrole anions 607 to 2-arylpyrroles 609-611 has been developed (Scheme 123) <20040L3981>. 

Arylpyrroles. Reaction with /V-tosylimines at the sp terminus of the pro-pargylbenzotriazole followed by intramolecular substitution (and aromatization-detosylation) represents a new synthetic protocol. 2-Hetarylpyrroles are also available by this method. 

Lu employed a phosphine-catalyzed [3-1-2] cycloaddition of methyl 2,3-butenedioate (8) with aromatic or heteroaromatic N-tosylimines 9 to afford the N-tosyl-3-pyrrolines 10 in good yields <97TL3461>. Aromatization of these substrates to the corresponding 2-arylpyrrole-3-carboxylates 11 is effected by dehydrogenation with DDQ in refluxing benzene. 

S93> The lithium anion adds to N-tosylimines to generate 3-(benzotriazolylmethyl)propargylsulfonamides. In hot ethanolic sodium ethoxide these undergo cyclocondensation to the 2-arylpyrroles. The cyclization evidently occurs via allenic isomers formed under the basic conditions. The synthesis can also be adapted to... 

Condensation of acetophenones and -dimethylaminonitroethene gives y-nitroenones which can be reductively cyclized to 2-arylpyrroles (Scheme 7) <74CB1499>. 

Organocopper intermediates formed by carbocupration of ethyl 4-(bis-trimethylsilylamino)but-2-ynoate undergo cyclization with aroyl chlorides to form 2-arylpyrrole-3-carboxylate esters (Equation (27)) <930M2478>. 

In 2014, the You group reported a highly efficient synthesis of enantio-merically enriched substituted piperidines by CPA (l )-32b catalyzed cascade hydrogenative dearomatization of substituted pyridines and AFC reaction with pyrroles (Table 6.3). The reaction of 3-benzoylpyridine with a wide range of 2-arylpyrroles proceeded smoothly, and high yields and ee were obtained for 3-acylpyridines bearing either an electron-poor or electron-rich aryl group. 

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