Some mechanistic aspects regarding the Suzuki-Miyaura reaction between selected ortho -substituted phenylboronic acids and 3,4,5-tribromo-2,6-dimethylpyridine

Atropisomers are very interesting stereoisomers having axial chirality resulting from restricted rotation around single bonds and are found in various classes of compounds. Substituted arylpyridines are an important group of them. A regio- and atropselective Suzuki-Miyaura cross-coupling reaction on 3,4,5-tribromo-2,6-dimethylpyridine was studied. Reactions with various amounts of -substituted phenylboronic acids with 3,4,5-tribromo-2,6-dimethylpyridine gave a series of mono- di- and triarylpyridine derivatives which allowed to draw conclusions about the order of substitution. Also, the observed selectivity in the case of -methoxyphenylboronic acid suggested an additional metal -chelation effect in the transition state, apparently not present in the -chloro analogues. The rotational barrier in selected atropisomers was determined on the basis of HT NMR and thermal epimerisation experiments. The structure of most presented atropisomeric derivatives of 2,6-dimethylpyridine was confirmed by single-crystal X-ray analysis. Racemic chiral, differently substituted atropisomers were also examined by H NMR spectroscopy in the presence of a chiral solvating agent. This regio- and atropselectivity may be generally applicable to other arylpyridine systems. A regio- and atropselective Suzuki-Miyaura cross-coupling process has been observed, giving an efficient access to a class of atropisomeric compounds. An opposite selectivity using a differently -substituted phenylbornic acid was observed.