Regioselective functionalization of 2,2′-bipyridine and transformations into unsymmetric ligands for coordination chemistry

Novel synthetic strategies for a series of unsymmetrically substituted 2,2'-bipyridines have been developed. These bipyridines have found use in some novel homoleptic and heteroleptic ruthenium(II) complexes. Two methods for regiochemical control of nucleophilic addition to bpy have been explored: (i) mono N-oxidation followed by cyanation and subsequent hydrolysis gave 6-carboxy-2,2'-bipyridine (4); (ii) mono N-methylation followed by the conversion into 6-bromo-2,2'-bipyridine (12) and subsequent nucleophilic addition of lithio-acetonitrile followed by hydrolysis of 6-cyanomethyl-2,2'-bipyridine (8) gave the homologous 2,2'-bipyridine-6-acetic acid (9). An established method of regioselective mono-ring alkylation of bpy using methyllithium yielded 6-methyl-2,2'-bipyridine (14), and the generation of the anion of 14 and subsequent addition to a chloromethyl oxazoline was applied to synthesize a second homologue, methyl 2,2'-bipyridine-6-propanoate (16). Structural determinations using H-1, C-13 and 2D NMR spectroscopy permitted complete assignments of all signals in the H-1 NMR spectra.