Direct arylation, of 2-phenylpyridine

Scheme 9.20 Rhodium-catalyzed direct arylation of 2-phenylpyridine (58).

In 1998, Oi etal. [18] reported the oxidative direct arylation of 2-phenylpyridine using tetraphenyl-stannane and Wilkinson s catalyst. A mixture of mono- and diphenylated products was obtained, with the major regio isomer the ortfio-substituted product. It was presumed that the solvent - 1,1,2,2-... 

Another ruthenium catalytic system based on [RuCl2(q -benzene)MOTPP] (5 mol%) [MOTPP = tris(4-methoxyphenyl)phosphane] and acetamide (20 mol %) as additive was applied in direct arylation of 2-phenylpyridine with arylchlorides in the presence of K2CO3 (3 equiv.) in 1,4-dioxane at 101 °C... 

Direct arylation can be very efficiently catalyzed also by other metal centers besides paUadium(II), in particular rhodium(III) and ruthenium(II). In 2009, the groups of Ozdemir and Bruneau jointly reported on the catalytic activity of ruthenium(II) compounds with o-xylylene-bridged, chelating dicarbene ligands for the direct arylation of 2-phenylpyridine. Good catalytic efficiencies were observed even with aryl chlorides as substrates, so that the process resulted in the predominant formation ofbis-o-arylated products (Fig. 20). ... 

Figure 20 Direct arylation of 2-phenylpyridine catalyzed by Ru(ll) complexes.

Secondly, there is the problem of orientation. In a reaction between pyridine and phenyl lithium which produced 69 per cent of 2-phenylpyridine, no trace of 4-phenylpyridine was formed sa 3-substituent usually directs arylation preferentially to the 2-position [Table 5,25) only the steric factor... 

The first example of Rh-catalyzed C-H coupling of 2-phenylpyridines with 7-azabenzonorbornadienes to provide czs-fused dihydrocarbazoles 39 was reported by Li and coworkers (Eq. (5.38)) [23]. The C-N bond forms via a double C-H activation, in which a seven-membered rhodacyclic complex is a key intermediate as a result of stereoselective insertion of the olefin into the Rh-C(aryl) bond. This strategy has also been employed for the synthesis of dihydrocarbazoles by using various directing groups. 

In 2001, Oi and Inoue [10a] reported a ruthenium-catalyzed C-H arylation with aryl halides, which utilized a 2-pyridyl group as directing group. For example, they found that 2-phenylpyridine can be reacted with an equimolar amount of... 

Copper has been demonstrated to mediate cyanation of aryl bromides and iodides through the activation of C-CN bonds (Scheme 20). Phenylacetonitrile [64], malononitrUe [65], and even acetonitrile as a reaction solvent [66] have been reported to serve as cyanating agents. 2-Phenylpyridines [67] and indoles [68] are directly cyanated by copper-mediated cyanation reaction using phenylacetonitrile, which is supposedly oxidized first at its benzylic position to give benzoyl cyanide, which further reacts with copper complexes to generate a cyanocopper species responsible for the cyanation event. Nevertheless, detailed mechanisms of these cyanation reactions remain elusive. 

It was especially observed that the second arylation or heteroaiylation can be performed only in water as the use of Ru(OAc)2(p-cymene) in NMP for 20 h leads only to 20% of conversiim of the monoaiylated product into the mixed diarylated product, whereas the direct homodiaiylation of the same 2-phenylpyridine with thienylchloride with the same catalyst in NMP needed only 12 h at 120°C to reach complete diheteroarylation [65]. These results show that in NMP the second direct... 

In later work, it was discovered that the use of heteroatom-substituted phosphine oxide (HASPO) combined with [RuCl2(p-cymene)]2 was even more competent than R2P(0)H. The direct o/t/jo-arylation was achieved with the less reactive aryl tosylates and aryl chlorides using substrates such as oxazolines, phenylpyridine and phenylpyrazole in the presence of K2CO3 in NMP at 120 °C. Interestingly, the selectivity of the product was tuned by changing the electrophile. Aryl chlorides produced the diatylated products while aryl tosylates generated monoaiylated products (Scheme 4). 

The iminophosphoranes (63), that are readily synthesized from 2-chloro-5-cyano-6-ethoxy-4-phenylpyridine-3-carboxaldehyde, were reacted with aromatic isocyanates to obtain directly several new 1,8-naphthyridines in an aza-Wittig/electrocyclic ring-closure process." Phosphazene (64) was reacted with phenyl isocyanate (or 4-chlorophenyl isocyanate) to give a carbodiimide which was cyclized to afford a series of new, 2-substituted 3-aryl-8,9,10,ll-tetrahydro-5-methyl[l]benzothieno[3,2 5,6]-pyrido[4,3-d]pyrimidin-4(3//)-ones." ... 

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