3-arylpyrrole

Photochemical [2 + 2] cycloaddition is a powerful way to produce cyclobutanes, which, in turn, are reactive synthesis intermediates. N-Methylpyrrole adds aldehydes via [2 -I- 2] photocycloaddition to give transient oxetanes with high regioselectivity Ring-opening produces 3-(oi-hydroxyalkyl)pyrroles which are oxidized easily to 3-arylpyrroles, such as 3-BUTYROYL-l-METHYL-PYRROLE. With a special apparatus, ethylene is conveniently added to 3-methyl-... 

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. 

The introduction of substituents at the 3-position of pyrrole has been actively pursued in recent years due to the importance of this class of compound in natural product synthesis. In contrast to the significant number of preparations of polysubstituted 3-arylpyrroles, there have been relatively few syntheses of simple 3-arylpyrroles. A literature survey on the preparation of 3-arylpyrroles showed that the methods reported include the reductive cycliza-tion of 2-arylsuccinonitriles, the base-induced ring-closure of arylvinamidinium salts, and... 

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>. 

The coupling of 3-pyrrolin-3-yl triflates with arylboronic acids leads to 3-arylpyrroles because of concurrent dehydrogenation. A caveat of the coupling involving haloanilines is that deamination also occurs to some extent. 

Font and co-workers (87JOC521) measured for 56 a barrier of 69 kj mol, very close to that of 50H2. The barrier about the C-C bond of the chiral 3-arylpyrrole 57 has been determined to be 96 kJ mol (93BSF779). In an hexakis(pyrazol-l-yl)benzene, 58, with two kinds of pyrazole rings, the experimental barrier, 94 kJ mol (97JCS(P2)2173), corresponds to the transition state connecting the ududud isomer to the uduudd one. 

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). 

Arylpyrroles are available from 3-iodopyrroles (Scheme 10). Lithiation in the 3-position in l-(triisopropylsilyl)-3-iodopyrrole followed by reaction of the lithio species with trimethyl borate and hydrolysis of the product gives the boronic acid. Coupling of the crude boronic acid with aryl halides under Suzuki conditions leads to the formation of... 

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