Regio- and atropselective synthesis of selected ortho-phenyl substituted arylpyridine derivatives

The SuzukieMiyaura cross-coupling reactions between 2,3,5-tribromo-4,6-dimethylpyridine and orthomethoxyphenyl or ortho-chlorophenyl boronic acids were studied. The use of limited amount of the boronic acid resulted in the regioselective formation of biarylated products. In the case of orthomethoxy-and ortho-chloro substituted series, the complete arylation furnished stable at room temperature atropisomers of different stereochemistry. This result may be attributed to the presence of additional transition state stabilisation caused by the complexation of the palladium atom with orthomethoxy group and this observation may be helpful in the stereoselective synthesis of analogous compounds. The structure of all obtained pyridine derivatives was unambiguously determined by NMR spectroscopy, as well as the single-crystal X-ray analysis. All compounds described are chiral entities and the presence of individual enantiomers were visualized by the NMR spectra with chiral solvating agent.