Arylation of pyridine

Carbonylation at the 3-position of a pyridine is illustrated in Scheme 130.197 In these processes the intermediate carbanion from arylation of pyridine can be trapped by iron pentacarbonyl and the ensuing acyliron... 

The homolytic arylation of pyridine has been studied somewhat more systematically but by no means exhaustively. Quantitative analysis of the phenylation products using various sources of phenyl radicals has been achieved by ultraviolet spectroscopic or gas chromatographic methods. The results of some recent determinations are given in Table XV. 

Relative Rates op Arylation of Pyridine at 40° and Partial Rate Factors0... 

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. 

Free Radical Processes. Homolytic alkylation and arylation of pyridines has been studied extensively and reviewed (U ). The products are almost invariably mixtures of several Isomers depending on the nature of the pyridine substrate, the free radical (audits method of generation) and the type of medium in which the reaction is carried out. Tho gh early reports suggested 2-, and -substitution exclusively, more sensitive analytical techniques have shown the earlier claims to be erroneous 6ind studies into the various factors affecting product formation have been reported (1 6-62). 

A catalytic system comprising [RuCl2(rf-CJI6) 2 (11) and PPh3 was disclosed by Oi, Inoue and coworkers for direct arylations of pyridine derivatives using aryl bromides as electrophiles (Scheme 18) [72],... 

Scheme 20 Proposed catalytic cycle for the C-H arylation of pyridines through iV-heterocyclic carbene formation [176]...

Campeau L-C, Rousseaux S, Fagnou K (2005) A solution to the 2-pyridyl organometallic cross-coupling problem regioselective catalytic direct arylation of pyridine V-oxides. J Am Chem Soc 127 18020-18021... 

Berman AM, Lewis JC, Bergman RG, Ellman JA (2008) Rh(I)-catalyzed direct arylation of pyridines and quinolines. J Am Chem Soc 130 14926-14927... 

Scheme 9.36 Palladium-catalyzed direct arylation of pyridine N-oxide (115).

Regioselective functionalization of unreactive carbon-hydrogen bonds, in particular, arylation of pyridines by using aryl iodide, silver acetate, and catalytic palladium acetate 06SL3382. 

Scheme 3 Palladium-catalyzed arylation of pyridine iV-oxides...

Scheme 5 Arylation of pyridine Al-oxides using aryl triflates...

A new approach for direct arylation of pyridine W-oxides with arylboronic acids through C-H functionalization has been developed (Scheme 45) [99]. This reaction can be performed at room temperature using catalytic silver (I) nitrate in the presence of potassium persulfate, thus giving 2-aryl derivatives of pyridine W-oxides. 

Scheme 9 C—H arylation of pyridines containing electron-withdrawing substituents at C3 or C4.

Scheme 11 Proposed catalytic cycle for the Pd-catalyzed C2-arylation of pyridine...

Scheme 9.5 Rhodium-catalyzed direct arylation of pyridine 1 with boronic acid 10.

Scheme 9.26 Ruthenium-catalyzed phosphine ligand-free direct arylation of pyridine 1.

Many examples exist of synthetically useful intermolecular paUadium-catalyzed arylations of Jt-excessive heterocycles [4, 7, 50-56]. The reaction has also been extended to the direct arylation of pyridine, diazine and azole N-oxides with aryl halides [57]. Interestingly, tuning the ligand and base allows selective sp or sp activation of alkyl pyridine or pyrazine N-oxides [58], Palladium-catalyzed sp activation of alkylanines [59] and benzyUc arylation of benzoxazoles has also been described [60]. 

---