2-Phenylpyridine, arylation

The activation of inert bonds provides a final indication of the further scope offered by Ru-NHC complexes. During the studies on phenylpyridine arylation, 43 was also shown to catalyze the regioselective H/D exchange in pyridines... 

Different primary, secondary aryl or heteroaryl manganese bromides 519 were prepared by reaction of activated manganese [prepared form manganese dichloride, lithium and a catalytic amount (15%) of 2-phenylpyridine as electron carrier, in THF] with the corresponding brominated compounds 516. These intermediates react with different electrophiles in THF at 0°C with or without copper chloride, to yield the corresponding products 20 (Scheme 144). ... 

The chemistry of aryl groups attached to the 7r-deficient heterocycles is unexceptional and much as might be expected. Thus, electrophilic substitution of phenylpyridines occurs exclusively in the phenyl ring. 4-Phenylpyridine gives mononitration products in the ratio o m p, 20 33 47 (68JCS(B)862, 71JCS(B)712). The oxidation of phenylpyridines can lead to either a pyridinecarboxylic acid or benzoic acid. 

In sharp contrast, homolytic arylation is unselective and gives low yields. Phenyl radicals attack pyridine unselectively to form a mixture of 2-, 3- and 4-phenylpyridines in proportions of ca. 53, 33 and 14%, respectively. The phenyl radicals may be prepared from the normal precursors PhN(NO)COMe, Pb(OCOPh)4, (PhC02)2 or PhI(OCOPh)2. Substituted phenyl radicals react similarly. 

Photolysis of aryl or pyridyl oxime esters in pyridine provides a-phenylpyridines as the major products together with bipyridyls (84TL3887). Rate constants for the addition of phenyl radical to protonated and non-protonated 4-substituted pyridines have been determined by studing the competition between phenyl radical addition and chlorine abstraction from carbon. The 4-arylpyridines were the major products, and no 3-substituted pyridines were observed. Among the solvents studied (MeCN, DMF, DMSO, and HMPA), MeCN gave the highest yields and selectivity (910PP438). 

Both diethyl (3-pyridyl)borane and diethyl (4-pyridyl)borane are readily accessible from 3-bromopyridine and 4-bromopyridine, respectively, via halogen-metal exchange and reaction with triethylborane [29-32], The two pyridylboranes have been coupled with a variety of aryl and heteroaryl halides, as exemplified by the coupling of diethyl (3-pyridyl)borane and 2-nitrophenylbromide to form phenylpyridine 39 [30, 31]. 

An electrophilic palladation by a phenyl palladium intermediate at C(3) and a C(3) to C(2) migration of a palladium species, followed by reductive elimination, is indicated. 2-Phenylpyridine has been formed by the reaction of pyridine and iodobenzene at 150 °C in the presence of phosphido-bridged ruthenium dimer complexes.49 A catalytic cycle involving one of the complexes in the system was proposed. Optimum conditions for the efficient and regioselective palladium-catalysed C(2) arylation of ethyl 4-oxazolecarboxylate (47) with iodobenzene have been presented.50... 

Benzylidene anilines formed from benzaldehydes and anilines have been found to undergo ortho arylation effectively when a ruthenium catalyst such as [RuC12(/ 6-C6H6)]2 is used in the presence of K2C03 as base (Eqs. 11 and 12) [17]. A polar solvent such as NMP is used. In this reaction the substrates have no acidic hydrogen and thus ortho metalation seems to occur via coordination of the neutral nitrogen to the metal center, as in the reaction of phosphinite (Scheme 3). Similarly, 2-phenylpyridine [18] (Eq. 13) and 2-phenyl-lH-imidazole (Eq. 14) [19] are arylated. 

Phenylpyridine is arylated by using aryltin reagents such as Ph4Sn in the presence of a rhodium catalyst (Eq. 15) [21]. The use of a halogenated solvent is important for obtaining a satisfactory yield. Although the precise mechanism is not yet clear, it is likely that a cyclometalated intermediate participates. 

The Hiyama cross-coupling of organosilanes is attractive as the intermediates are often easy to prepare and the silicon by-products are environmentally benign. A one-pot synthesis of 2-aryl-3-methylpyridines from 2-bromo-3-methylpyridine was developed (Scheme 25) <2003JOM58>. Both 2- and 3-bromopyridine cross-couple with phenyltrimethoxysilane to afford the corresponding phenylpyridines in good yield <19990L2137>. 

These palladacycles also undergo addition to iodobenzenes. 2-Phenylpyridine is arylated at the ortho-position with /vzra-substituted iodobenzenes in good yield in the presence of 5mol% Pd(OAc)2 and stoichiometric amounts of AgOAc <2005OL3657>. 

The reaction of a lithium alkyl or aryl with dry pyridine involves the formation of a dihydro derivative (103) which, on heating or on being oxidized with molecular oxygen in the cold, furnishes the 2-substituted pyridine 104. Alternatively, 103 may be treated with water to give the 1,2-dihydro derivative which is converted to 104 by oxidation with picric acid (in which case the picrate of 104 is the product isolated) or with chloranil.229 No 4-phenylpyridine could be detected by gas chromatography in the reaction with phenyllithium.230 Support for... 

The free-radical arylation of pyridine N-oxides has not been studied systematically, alkylation not at all. When pyridine A-oxide was treated with benzene- and p-chlorobenzenediazonium salts only the 2-arylpyridine jV-oxides were isolated.393 No mention was made of the formation of the 3- and 4-aryl derivatives expected to be produced as well. The phenylation of pyridine N-oxide (diazoaminobenzene at 131° or 181° was found to be the most convenient source of phenyl radicals) was reinvestigated,394 and the reactivities of the nuclear positions found to be in the order 2 > 4 > 3, which is also that predicted6 on the basis of atom localization energy calculations. 2-Phenyl-pyridine N-oxide formed 71-81% of the total phenylation products, whereas the 3-isomer comprised only 5.6-9.6% of that total. The phenylpyridines were found among the by-products of the reaction. 

The first aryl to aryl migrations were observed between the o-position and the o -position in a biphenyl system [51] and an analogous phenylpyridine system [52] (Table 1). While studying the Heck reaction of o-iodobiphenyls and analogues,... 

The scope of this reaction with respect to the 2-arylpyridine includes substrates with ortho substituents such as 3-methyl-2-phenylpyridine, 2-(2-methylphenyl) pyridine, and 2-(l-naphthyl)pyridine that result in singly arylated C-H/C-M coupling products. The sensitivity of this reaction to sterics is further evidenced by the selective phenylation of 2-(2-naphthyl)pyridine at the 3-naphthyl position while the more sterically hindered 8-naphthyl position is unreactive. Both electron-neutral (Ph4Sn) and electron-rich ((4-MeOC6H4)4Sn) tetraarylstannanes have been shown to participate in this reaction, but the reaction with ortho substituted and/or sterically hindered stannanes has not been demonstrated. Functional group tolerance for groups other than aryl ethers has not been reported. 

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