Phenyl pyrrole derivatives

Pyrrolnitrin - A unique, substituted 3"Phenyl pyrrole derivative was reported by Arima and co-workers in 19614-. This compound, produced in Jhe fermentation of several species of the genus Pseudomonas,42 found to have structure III. 

While phenyl pyrrole derivatives have not been isolated from higher plants, a number of plant alkaloids have been shown to be derived from tryptophan (Manske, 1965). Several of these plants, such as the calabar bean (Physostigma venenosum Balf.) and the family Calycanthaceae [Calycanthus L. and Chimonanthus Lindl.), yield compounds, e.g. physostigmine (VIII) and folicanthine (IX) whose biosynthesis may follow a pathway similar to that of pyrrolnitrin. 

The formation of 2H-pyrroles (21) and a pyrrole derivative (22) from the reaction of 3-phenyl-2//-azirines and acetylenic esters in the presence of molybdenum hexacarbonyl is intriguing mechanistically (Schemes 24, 25).53 Carbon-nitrogen bond cleavage must occur perhaps via a molybdenum complex (cf. 23 in Scheme 26) but intermediate organometallic species have not yet been isolated.53 Despite the relatively poor yields of 2H-pyrrole products, the process is synthetically valuable since the equivalent uncatalyzed photochemical process produces isomeric 2H-pyrroles from a primary reaction of azirine C—C cleavage54 (Scheme 24). 

Pyrrolizin-3-ones may also be obtained by FVP of 3-(pyrrol-2-yl)propenoate esters such as 62, 69, and 74. Also, benzo-annulated pyrrolizinone 17 was obtained by FVP of 2-(tf-methoxycarbonyl phenyl (pyrrole <1999J(P1)2047>. FVP of alcohols 77, 78, and 79 led to 3//-pyrrolyzine derivatives 1, 192, and 193, respectively, in good yields (66-95%). These transformations proceed by elimination of water and subsequent electrocyclization of the in situ-generated cumulene (Scheme 44) <1999J(P1)2049>. 

Thieno[2,3- ]pyrrole derivatives 462 were easily synthesized in two different ways using phenyl isothiocyanate and activated methylene compounds (Scheme 55) <2001SL1731>. The relative order of thiophene or pyrrole ring formation was investigated <2003T1557>. 

Scheme 2.27. Pyrrole derivatives from phenyl isocyanide and 2-isocyanopyridine.

There are few studies on the metal triflate-catalyzed addition of pyrroles to a, 1-unsaturated compounds <2001 AGE 160, 2001TL8063>. The Friedel-Crafts reaction of homochiral pyrrole derivatives 450 with a,P-unsatu-rated esters catalyzed by metal triflates furnished conjugated addition products 451 in good yields without racemiza-tion (Equation 107) <2004S2574>. The addition worked regioselectively at C-5 of pyrrole. The best yields were obtained by using yttrium triflate and methyl 4-phenyl-2-oxobut-3-enoate. The diastereoisomers were separated by column chromatography. 

Starting from the l-[(trifluoromethyl)phenyl]pyrroles 753, 756, and 760, the mono- 754, 758, 759, 762, and 763 and the dicarboxylated 755, 757, and 761 derivatives were selectively prepared as shown (Equation 178, Schemes 149 and 150) <1999T7881>. The regioselective formation of the monocarboxylic acids could be rationalized in light of the data... 

Inclusion of bismuth atoms in heterocyclic ring complexes has been actively investigated for a number of years. Complexes of the type (17), for example, l-phenyl-2,5-dimethylbismole, have been sought for comparison with pyrrole derivatives and for information about the degree of aromaticity in its heavier analogs. Compound (17) is prepared via the addition of 2(Z),5(Z)-dilithio-3,4-dimethylhexa-2,4-diene to PhBil2 in 28% yield. This heterocycle is converted to the dibismuthine in the standard fashion treatment of (17) with Na in liquid NH3 followed by addition of 1,2-dichloroethane. 

The thermocatalytic Rh(ll) decomposition of diazo malonate in the presence of 3-phenyl-2/7-azirine 772d was proposed to give rise to an azirinium ylide 803 <2004TL6003>. This reactive ylide is preferentially transformed into 2-azabuta-l,3-diene derivative 804 or, with excess diazo compound, via reaction with the Rh-carbenoid, forms the 3,4-dihydro-2/7-pyrrole derivative 806 via intermediate 805 (Scheme 196). 

Addition of a-aminonitriles to an a,p-unsaturated ketone affords 1,4-diketones. High yields are also observed in 1,4-additions to ethyl acrylate or acrylonitrile. o-Phenyl-a-(A -morpholino)acetonitrile gives good yields of 1,4-adducts with methyl crotonate, methyl methacrylate, diethyl maleate and ethyl propiolate under catalysis of sodium methoxide in THF. Reaction of the lithium salt of (41) with methyl acrylate is reported to give pyrrole derivatives (Scheme 18). 

Using diazoalkanes results in the formation of isomeric mixtures of cycloadducts.Unlike some reactants (phenyl azide, tosyl azide and diphenylnitrilimine), benzonitrile oxide, diazomethane, and A-phenylbenzylideneamine A-oxide underwent [3 4- 2] cycloaddition on mixing with lumisantonin using A -phenylbenzylideneamine A-oxide, however, gave the product cycloadduct in 8% yield.Dihydropyrazoles were obtained in some cases.Furthermore, pyrrole derivatives were obtained in low yield by intramolecular addition of an azomethine ylide to an a- and / -monocyclopropyl acrylate moiety. 

Unlike the bis[4-(dimethylamino)phenyl]squaraine derivatives, the pyrrole derivative 25 (Structure 7) is relatively nonfluorescent (cjif = 0.08) with an extremely short excited singlet state lifetime (tf = 222 ps) [70]. The intersystem... 

The cycloaddition of 223 with diazoethane in 1,4-dioxane gave the nitro-pyrazoline 227, whose aromatization was effected with HCl to give pyrazole 228 (91MI7). 3-Methyl-2-(4-nitrophenyl)-4-phenyl-l,3-oxazolium-5-olate (226) reacted regioselectively with 223 to give the respective pyrrole derivatives 225, which could be deacetylated with sodium methoxide (89MI4). 

In one of the rare examples of the use of pyrrolyl radicals, Merz (99AGE1442) achieved dimerisation of 2-iodo-3,4-dimethoxy-5-phenyl pyrrole using high temperatures in the presence of copper. D Auria (97H(45)1775) studied the photochemical behaviour of 2-iodopyrrole derivative 237 in benzene (Scheme 65). 

The related cycloaddition of the more reactive 7-dimethylamino-l-methyl-l//-azepin-3(2//)-one with 2 mol of methyl propiolate <93CC1417) gives the trisubstituted pyrrole derivative (46). In this example, the initially formed phenyl derivative (45) reacts with a further molecule of ester which is then followed by a cyclocondensation reaction to give (46) (Scheme 8). 

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