Pyrroles arylations

A short and efficient route to enantiopure 3.5-di aryl pyrrol i/,idines using chiral nitrodiols has been reported (Scheme 10.20).123... 

Only 3-diazopyrroles have been prepared by diazotization of the corresponding amino compounds. The reaction is carried out in acetic acid with a stoichiometric amount of nitrite in the case of simple aryl pyrroles. The diazopyrroles were isolated in good yields upon alkalinization with sodium carbonate, and care was taken to control temperature during diazotization and neutralization (61JOC3790). 

UV Absorption of Alkyl and Aryl Pyrroles and Their Conjugate Acids... 

The electrochemically induced S l reaction of aryl chlorides with redox mediators and pyrrole anion gave mainly 2-aryl pyrroles (52-67%) and, in a lower amount, 3-aryl pyrroles... 

Stille and Suzuki cross-coupling reactions failed when the authors tried to obtain the mono-arylated pyrrole under different conditions. As a consequence, these types of coupling reactions would not seem to be useful in providing access to differentially di-arylated pyrrole systems... 

With bulky N-alkylpyrroles, 2,4-dilithiated products can be obtained also . N-Aryl pyrroles provide both o- and a-lithiations " . 

The, V-pyrrolylzinc chloride (75) can be generated and coupled in situ with aryl bromides to give the expected 2-arylated pyrroles 77 in good to excellent yields [62]. Some aryl chlorides and iodides also couple with 75. 

Arylene-bis-(pyrrole dicarboxylic acid anhydrides) were prepared by the condensation of two moles of diethyl diacetyl succinate with one mole of aromatic diamine, followed by hydrolysis and dehydration. Condensation of these novel dianhydrides with various aromatic diamines resulted in the formation of poly (amic acids) which were further condensed to polyimides. If the diethyl diacetyl succinate and aromatic diamine were reacted in equimolar quantities an N-(amino aryl) pyrrole diester was formed which can be further condensed to give polyimide directly. 

The initially prepared poly (amic acids) lose water in the range of 150-230°C to form the polyimide which shows thermal stability up to 400 C. Heating of the N-(amino aryl) pyrrole diester monomer under vacuum at 200-250°C was found to be sufficient for conversion to the polyimide. These pyrrole derivative monomers therefore are easily obtained from relatively inexpensive starting materials and appear to offer promise of being an attractive route to thermally stable polymers at reasonable cost. 

Synthesis of N-(amino aryl) pyrrole dicarboxylate monomer. This type of polyimide precursor was prepared by the method of Knorr, who first described these preparations almost 100 years ago. The preparation proceeds readily by refluxing of ethyl diacetyl succinate with... 

Pyrroles.—Formation. A general synthesis of 2-aryl-pyrroles (112) is by cycliz-ation of the esters (111), which are obtained from unsaturated aldehydes and methyl azidoacetate. Thermolysis of the acetylene (113 Ar = p-MeC6H4) gives Al-(p-tolyl)pyrrole with the elimination of p-thiocresol. The pyrrole derivative (115) is the product of the action of benzylamine on tri-(t-butylthio)cyclopropenylium perchlorate (114). Azoalkenes combine with fi-dicarbonyl compounds or with enamines to yield derivatives of Al-aminopyrrole thus the ester (116) and ethyl acetoacetate form (117). The base-catalysed addition of methyl propiolate to toluene-p-sulphonylmethyl isocyanide, T0SCH2NC, gives the ester (118). The dipolar cyclo-adduct (120) of piperidinocyclopentene to the azo-compound (119) forms the A-(tosyl-amino)pyrrole derivative (121) and piperidine on heating. ... 

Atropisomeric 2-aryl pyrroles (205) have been prepared from N-(S)-phenylethyl imines (204) through an efficient tandem Michael reaction-azacyclization. Diastereomers were obtained in moderate or high de, they were separated into optically pure compounds. These compounds showed high rotational barriers since no diastereomerization was observed at 110 °C (04TA139). 

Table 5. Selected examples of a reported combination of substituents situated in blocking positions in atropisomeric N-aryl pyrroles (10WO42622)...

Figure 3 Proposed mass spectral fragmentations of iV-aryl pyrroles.

In our original article on this work, alternative sequences to pyridinopyrroles were developed, one of which also gave easy access to aryl pyrroles (46) and pyrrolidines (47) from an intermediate keto aldehyde (48) (Scheme 18.14). 

The utility of the Paal-Knorr reaction allows it to stiU remain at the forefront of organic chemistry for the preparation of highly complex substrates and drug-like compounds. The Paal-Knorr reaction was used to synthesize iV-aryl pyrroles 25 with an azide group on the aryl ring. These substrates were subsequently employed in a tandem azide-alkyne 1,3-dipolar cycloaddition reaction to synthesize medicinally important molecules with a diazepine scaffold 27 (14OL560). 

A cyclocondensation reaction between alkynes 29 and amines 28 to give arylated pyrroles 30 was developed using catalytic base to drive the reaction forward. This procedure was altered so that tri-substituted pyrroles can be synthesized by first dimerizing the alkyne under copper catalysis and then subjecting the product to KOH in the presence of amines (14T8252). 

Pyrroles can be synthesized from 3-pyrrolines 39 which can be prepared from a Crabbe reaction of propargyl sulfonamides 38 and selective cycloisomerization of the resulting allene intermediate. Subsequent oxidation of 3-pyrrohnes with 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) lead to 2-alkyl and aryl pyrroles 40 in this domino process (14EJO2305). 

Arylpyrroles have been generated from the reaction of arylketoximines with acetylene. Under standard Trofimov conditions (KOH/DMSO, acetylene), several aryl pyrroles can be prepared in respectable to good yields. Formation of the nonvinylated product was observed in good yields, and similarly for the iV-vinyl pyrroles. The effect of the KOH loading on the reaction yield showed an optimum at 30 wt%, and the effect of temperature... 

Modification of the initial route also allowed the preparation of 2-aryl-substituted pyrroles. The aryl pyrrole motif occurs in various natural products such as in the broad-spectrum antibiotic pyrrolonihin and in the insecticide dioxapyrrolomycin. Therefore, new routes to these structural types are always important. For example, immobilized reagents and scavengers may conveniently be used to prepare a hbrary of 3-aryl-substituted pyrroles as shown in Scheme 6.6. 

Ackermann [23] applied his own catalyst to the directing-group-assisted C-H/C-X coupling of heterocycles such as pyrroles, indoles, and thiazoles. For example, pyridylpyrrole 26 can be coupled with 4-bromoanisole in the presence of their ruthenium catalyst to afford arylated pyrrole 27 with complete C2 selectivity. 

Dlmethyl-Af-alkyl/aryl pyrrole (3) 20 entries (yield 60 - 98%)... 

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