Indole 3-bromo-, reaction with pyrrole

Pyridinium bromide perbromide efficiently brominates pyrroles already substituted by electron-withdrawing substituents and also gives a high yield of 3-bromoindole in its reaction with indole. In conjunction with sulfuryl chloride, it has been used in the synthesis of 3-bromo-2-chloro-, 2-bromo-3-chloro- and 2,3-dibromo-indole (81SC253). 3-Methylindole reacts with A-bromosuccinimide in acetic acid to give the 2-bromo derivative which reacts further with an excess of A-bromosuccinimide to yield 2,6-dibromo-3-methylindole (B-70MI30500, 72HC(25-2)127) whilst in aqueous or alcoholic media, 3-bromo-3-methylox-indole is produced (cf. Scheme 15). All of these reactions proceed via the 3-bromo-3A-indolium cation, but the course of the reaction depends not only upon the orientation or... 

Pyrroles and indoles also appear to behave as 2 7r-electron systems in their reactions with with the a-bromo oxime (276) and with the a-bromo semicarbazone (277) under basic... 

Pyrrole, indole, and carbazole give a color reaction with 2-bromo-2-nitroindandione-1,3 in glacial acetic acid (129, 130),... 

Such a reversible blocking of the 2-position by sulfenylation was of particular interest in the synthesis of bromo-derivatives of indolyl-3-propionic acid. Specific bromination or nitration of the benzene ring of an indole is normally difficult to achieve, since the pyrrole ring also will react with electrophilic reagents. As an example, 5-bromoindole-3-propionic acid has been prepared using this reversible protection, that is by bromination of the 2-sulfenylated compound and removal of the arylthio group by the two consecutive reactions with NBS and NaBKi (727). 

Under conditions more similar to those of the Reimer-Tiemann reaction 3-bromopyridine was obtained from pyrrole and bromo-form. Treatment of pyrrole with chloroform and aqueous alkali gave pyrrole-2-aldehyde curiously, the formation of 3-chloropyridine under these conditions does not appear to have been reported, in spite of being frequently quoted. However, indole gave both indole-3-aldehyde and 3-chloroquinoline under these conditions [Eq. (10)]. 

Among early reported Pd-catalyzed reactions, the Mori-Ban indole synthesis has proven to be very useful for pyrrole annulation. In 1977, based on their success of nickel-catalyzed indole synthesis from 2-chloro-fV-allylaniline, the group led by Mori and Ban disclosed Pd-catalyzed intramolecular reactions of aryl halides with pendant olefins [122]. Compound 102, easily prepared from 2-bromo-lV-acetylaniline and methyl bromocrotonate, was adopted as the cyclization precursor. Treatment of 102 with Pd(OAc)2 (2 mol%), Ph3P (4 mol%) and NaHCQ3... 

Substituted nitrosoalkenes, prepared in situ from corresponding a-bromo oximes, can be added to furan , pyrrole or indole to afford fused oxazine derivatives. Recently, there was reported a preparation of novel heterocyclic oxazinotetrahydroquinoline 355 and 356 or oxazinotetrahydroisoquinoline 357 derivatives by reaction of the corresponding dihydroquinolines or dihydroisoquinolines with a-bromo oximes 354 in the presence of NajCOj in CH2CI2 (equation... 

Examples of related photochemical (hetero)arylations are the pentafluoralkyla-tion of pyrroles and indoles by irradiation in the presence of pentafluoroiodo-benzene or of pentafluorophenyl perfluoroalkanesulfonates [97], and presumably also the acetone-sensitized photocoupling of 5-bromo-l,3-dimethyluracil (47) with indoles. The latter reactions apparently follow an ET path, rather than the homo-lytic debromination which occurs on direct irradiation (Scheme 32) [98]. A different arylation leads to 2,5-dihydro-2-(4 cyanophenyl)-5-methoxyfuran on irradiation with 1,4-dicyanobenzene in methanol [99]. 

The first reports of palladium-catalyzed arylation (equation 39) of azoles occurred with catalysts bearing DPPF as the ligand125. These reactions of indole, pyrrole and carbazole with activated aryl halides were carried out at 80-100°C. The reactions of indole and pyrrole with unactivated aryl halides such as bromobenzene, 4-bromo-r -butylbenzene and 3-bromoanisole occurred in high yields. However, the conditions of these reactions were more severe than those typically necessary to conduct palladium-catalyzed coupling of aryl halides with amines (equation 40). 

Indeed, a variety of heterocyclic compounds, such as thiophenes, dithiophenes, pyrroles, indoles, or carbazoles can be involved as carbon-centered nucleophiles in these reactions to modify the pyrimidine ring (Scheme 31) [120-122]. For instance, it has been shown that 5-bromopyrimidine reacts with dithiophene into the corresponding 5-substituted pyrimidine due to palladium-catalyzed aryl-aryl C-C cross-coupling reaction. On the other hand, 5-bromo-4-dithiophenyl-substituted pyrimidine was prepared from the same starting material through the SH (addition-oxidation) reaction catalyzed by a Lewis acid in the presence of potassium... 

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