Chiral Hexahalogenated 4,4′-Bipyridines

The
preparation of 27 isomers of chiral hexahalogeno-4,4′-bipyridines
by means of two complementary methods is described. The first one
is convergent and based on the LDA-induced 4,4′-dimerization
of trihalopyridines, whereas the second method is divergent and achieved
through regioselective halogenation reactions of 4,4′-bipyridine-2,2′-diones.
Iodine in 2,2′-positions of the 4,4′-bipyridines was
introduced by a copper-catalyzed Finkelstein reaction (Buchwald procedure)
performed on 2,2′-dibromo derivatives. Selected compounds of
this new family of atropisomeric 4,4′-bipyridines were enantioseparated
by high performance liquid chromatography on chiral stationary phases,
and the absolute configurations of the separated enantiomers were
assigned by using X-ray diffraction analysis. The latter revealed
that various halogen bond types are responsible for crystal cohesion.