Chelating biaryls

These materials can be broadly classified as three types, viz. phenyl, heteroaromatic and chelating biaryl. 

In 1956 it was found that when pyridine is refluxed with a modified Raney-nickel catalyst, 2,2 -bipyridine (1) is formed in satisfactory yield. The isomeric bipyridines could not be detected, and the product was readily purified. Similar heterocyclic biaryls have been formed in the same way from substituted pyridines and from some related compounds, the yield being dependent on the nature of the compound. The reaction has become the method of choice for the preparation of 2,2 -bipyridine, and it is now used on an industrial scale. Bipyridyls are of particular importance as chelating agents. 

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. 

The chiral center most frequently encountered is the asymmetric carbon atom, a tetrahedral C atom, bonded to four different substituents. Chiral centers of this type are known for many other elements (4). However, chiral centers are also found in other polyhedra, e.g., the metal atoms in octahedral compounds containing three bidendate chelate ligands. Chirality axes, present in the atrop isomers of ortho-substituted biaryls, occur in coordination chemistry in appropriately substituted aryl, pyridyl, and carbene metal complexes. Well known examples of planar chirality in organometallic chemistry are ferrocenes, cymantrenes, and benchrotrenes containing two different substituents in 1,2- or 1,3-positions relative to each other (5-5). 

The presence of chelating groups in those complexes is necessary to stabilize the intermediate aryl-palladium complex for isolation but it does not seem necessary to cause palladation. The chelating group does, however, tremendously accelerate the palladation. Aromatic compounds reactive to electrophilic substitution apparently undergo palladation with palladium acetate in acetic acid solution fairly readily at 100 °C or above. Of course, the arylpalladium acetates presumably formed, are not stable under these conditions, and they decompose very rapidly into biaryls and palladium metal 34,35,36) ag do aryl palladium salts prepared by the exchange route 24>. If the direct palladation is carried out in the presence of suitable olefins, arylation can be achieved, so far, however, only in poor yields, arid with concurrent loss of stereospecificity and formation of isomers and other side products 37.38). 

Chelation-assisted C-H/olefin coupling can be applied to the atroposelective alkylation of biaryl compounds. The reaction of 2-(l-naphthyl)-3-methylpyri-dine with ethylene using [RhCl(coe)2]2 where coe is cyclooctene, and PCy3 results in the formation of an ethylation product in 92% yield (Eq. 21) [20]. In place of the PCy3 ligand, the use of (R) - (1 - [ (S) - 2- diphenylphosphino ] ferro-cenyl)ethyl methyl ether [(R),(S)-PPFOMe] leads to the atropselective alkyla-... 

Rajanbabu and coworkers [75] and Hoveyda and coworkers [6,7,78] have used the 1,1 -biaryl scaffold to mount the NHC unit on it (as well as the additional functional group to complete the necessary chelate motif). Another possibility is presented by starting from the... 

The other primary application of asymmetric Grignard coupling reactions has been in the synthesis of axially chiral binaphthyl and biphenyl derivatives. Hayashi performed a binaphthyl synthesis (equation 6) in 95% ee using a nickel catalyst and ligand (7), a P-O chelating analog to (3). For a similar synthesis of chiral biaryls (equation 7) ligand, (8) was found to yield the most successful results (93% ee). ... 

When the alkylation of 2-atylpyridines with olefins via a C-H bond cleavage was carried out with the aid of Ru(COD)(COT) (COD = 1,5-cydooctadiene COT = 1,3,5-cyclooctatriene) and the chiral phosphine (R),(S)-PPFOMe ((R),(S)-PPFOMe = (R)-T [(S)-2-(diphenylphosphino)ferrocenyl]ethyl methyl ether), the alkylation product 5 was obtained in 15% yield with 15% e.e. (Eq. 9.7) [22]. Although the chemical and optical yields are inadequate, this result suggests that the atropselective alkylation of a biaryl compound is possible by means of a chelation-assisted C-H/olefin coupling. 

Cis-trans isomerism around single bonds has been widely used in supramolecular chemistry, in particular with bulky biaryl compounds such as the metal-chelating agents bipyridines and sterically hindered binaphthyl motifs. In these compounds, a moderate barrier to rotation exists due to the resonance of the two con-... 

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