NEW SYMMETRICAL AND UNSYMMETRIC POLYFUNCTIONALIZED 2,2'-BIPYRIDINES

Recently, a large number of biheterocycles have been synthesized in order to build macrobicyclic cryptates. To pursue investigations in this field, we prepared new symmetric and unsymmetric functionalized bipyridines and we describe here two synthetic strategies leading to new tetrasubstituted 3 to 15 and trisubstituted 17 to 29 bipyridines. Modification at the alpha,alpha'-methyl groups and introduction of functionalities in the 4,4'-positions have been performed after N-O activation of the starting 6,6'-dimethyl-2,2'-bipyridine unit. In the case of cyano and hydroxymethyl groups, alkylation of the N-O function followed by a nucleophilic attack with the CN anion or an hydroxymethyl radical allowed us to obtain the dissymmetric species. To understand observed differencies between cyanation and hydroxymethylation processes, the unstable and hygroscopic N-methoxybipyridinium salt 30 has been isolated and characterized by nmr. Dibromomethyl compounds 8, 15, 29 were finally obtained in good to moderate yields by the Boekelheide rearrangement followed by a pseudohalogen exchange.