1- Arylpyrrole derivatives

The 1-arylpyrrole derivative (319) reacts normally with cyanide ions to give the 2-cyanomethylpyrrole (320), which subsequently undergoes an intramolecular cyclization to yield (321) (77FES339). The 2-cyanomethylpyrrole (322) also cyclizes, when treated with ammonia, to give the 17/-pyrrolo[3,2-c]pyridin-4-one (323) (80TL3135). 

These workers have also used 3-iodopyrrole 103 to prepare the corresponding tin derivative 104 for Stille couplings to furnish 3-arylpyrroles 105 [78], These pyrrole derivatives are important for the synthesis of (i-aryl-substituted porphyrins for studies of heme catabolism. Also synthesized in this study were compounds 106 and 107 [78]. 

Another entry into the preparation of 3-arylpyrroles starts with the reaction of the 3-iodopyrrole derivative shown in 6.28. with hexabutyl-distannane in the presence of a palladium catalyst. The formed intermediate was reacted, in the presence of a similar catalyst system, with different aryl iodides to give the desired products in good to excellent yield38 It is worth mentioning that the presence of a formyl group in the 2-position of he pyrrole had no adverse effect on the efficiency of the couplings. 

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%. 

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). 

The phosphorylated derivatives 92 [87] and N-arylpyrroles 93, having biological activity [88], were synthesized from 2-formylpyrroles ... 

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>... 

The dialkylamino group of a 2-dialkylaminomethyl pyrrole can also be displaced by various nucleophiles. In a typical example, displacement of trimethylamine from the quaternary salt derived from the Mannich base of a 1-arylpyrrole gives an azide which can be reduced to give the aminomethylpyrrole (Scheme 129). 

Facile synthesis of simple 3-arylpyrroles from pyrroline by tandem Suzuki dehydrogenation reaction is depicted in Scheme 229. Thus, treatment of l-benzyl-2,5-dihydro-l//-pyrrol-3-yl trifluoromethanesulfonate 1195 (prepared in 55% yield from l-benzyl-3-pyrrolidinone 1194 by trapping the enolate with a triflating reagent), with boronic acid derivatives leads to the formation of 3-arylpyrroles 1196 in good yields (65-74%) <2000TL3423>. 

Arylpyrroles, substituted or unsubstituted at the nitrogen, undergo a much more drastic oxidation than alkyl derivatives by the action of hydrogen peroxide. In most cases opening of the heterocyclic ring occurs, both at the bond between the heteroatom and the a-carbon and between the a- and )8-carbon atoms. From 2,5-diphenylpyrrole in acetic medium benzoic acid and acetophenone are formed.51 From 2,3,5-triphenyl-pyrrole (58, R = H) the product is 59,61 while from 58 (R = benzyl) the compounds 60 (R = benzyl) and 61 are produced.62 Other pyrroles that were found to behave similarly are listed below. 

Dehydrogenation. Aromatization of 3,4-diaryl-2,5-dihydro derivatives of furan, thiophene, and A-arylpyrrole is accomphshed in 80-91% yield by heating with CuBry (3 equiv.) in EtOAc. ... 

Pyrrole itself tends to give tars under radical conditions, probably by way of initial N-hydrogen abstraction, but some A -substituted derivatives will undergo preparatively useful arylations, with attack taking place predominantly at an a-position. More efficient routes to arylpyrroles depend on transition metal-mediated coupling processes (see section 2.7.2.2). A -Methylpyrrole is attacked by electrophilic benzoyloxy radicals at its a-positions. ... 

Attempts to resolve the atropisomers of the free acid form were unsuccessful probably due to a too low barrier. 3-Arylpyrrole 210 was used to construct the verdin derivative 211 that showed syn (meso) and anti (d,l) forms in their NMR. The ratio was strongly dependent on the solvent. Variable temperature NMR experiments of verdin 211 showed coalescence at 413K the barrier to interconversion was equal to 89.5 kj mol (02T7411). 

Addition to arylidene derivatives of cyanoacetate esters leads to adducts which can be aromatized and decarboxylated to 4-arylpyrrole-3-carbonitriles (Scheme 78) <92Mi 203-03>. 

---