Pyridine biaryls derived from

Several substituted pyridines have been examined using the degassed Raney nickel, and the results are summarized in Table I. As all the biaryls obtained formed colored chelates with either ferrous or cuprous ions, they must be derivatives of 2,2 -bipyridine. Structural ambiguities cannot arise with 2,2 -bipyridines derived from 2- and 4-substituted pyridines but 3-substituted pyridines could conceivably give three isomeric 2,2 -bipyridines (e.g., 3, 4, 5). In fact, however, each 3-substituted pyridine so far examined has given only one 2,2 -bipyridine. 

Reaction of -picoline over degassed Raney nickel was found to give 5,5 -dimethyl-2,2 -bipyridine (5), the structure of which was established by its synthesis from 2-bromo-5-methylpyridine. Oxidation of this dimethyl-2,2 -bipyridine, and similar oxidation of the diethyl-2,2 -bipyridine derived from 3-ethylpyridinc, gave the corresponding dicarboxylic acid and the same acid was produced by the action of degassed Raney nickel on sodium nicotinate (in water) or on ethyl nicotinate. These transformations established the 5,5 -substitution pattern for three 2,2 -bipyridines derived from 3-substituted pyridines but such evidence is not available for the biaryls... 

In the total synthesis of ( )-WS75644B 360, a biaryl endothelin converting enzyme inhibitor, pyrone 357 derived from kojic acid was converted to pyridone 358 by reaction with concentrated ammonium hydroxide in a sealed flask at 90 °C. The resulting pyridine was subsequently converted to 2,4,5-trisubstituted pyridine 359 and ultimately elaborated to complete the total synthesis (Scheme 54) <1997TL1297>. 

Key step of the synthesis of compound 15, a derivative of amino acid 6, is an asymmetric Sharpless aminohydroxylation. The central building block 16 (amino acid 4), however, was built up from 4-aminobenzoic acid by an asymmetric dihydroxylation (AD) in 12 steps. Coupling of the biaryl fragment 19 with the corresponding amino acid derivatives (Scheme 6) gave tripeptide 20. By treatment with CuBr SMc2, K2CO3 and pyridine in acetonitrile under re-... 

Biaryls can also be derived (7(>-90%) from mercury salts, ArHgX, using methodology very similar to a normal Ullmann coupling (copper powder, pyridine, reflux), except that a catalytic amount of PdCh is alsorequired. Less basic solvents do not lead to such good yields, but otherwise the reaction charac-... 

Mechanistic studies supported the evidence that arylcopper compounds are intermediates in the synthesis of biaryls [60, 61]. This observation smoothed the way for the efficient synthesis of unsymmetric biaryls in a two-step procedure consisting, first, in the preparation of an, e.g. thienylcopper derivative followed by the treatment with different aryl halides. 2-Thienylcopper 42, for example, is prepared from the corresponding Li—Ti—H 9 or Grignard derivative and a copper(I)halide and is then reacted with iodo- or bromoarenes in pyridine or quinoline. By this procedure e.g. H-T2-H 2 is formed in 42% yield by the reaction of Cu-Ti-H 42 and 2-iodothiophene 8 [61] [Eq. (14)]. Analogously, 2-(/i-nitro-phenyl)thiophene is obtained in 70% when Cu—Ti—H 42 is treated with />-iodo-nitrobenzene. Note that the formation of undesired symmetric biaryl products is avoided [60, 61, 63]. 

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