Lithiation of Prochiral 2,2′-Dichloro-5,5′-dibromo-4,4′-bipyridine as a Tool for the Synthesis of Chiral Polyhalogenated 4,4′-Bipyridines

Lithiation of the achiral tetrahalogenated
4,4′-bipyridine 1 with alkyllithiums was investigated. n-BuLi
was found to induce either the chlorine-directed deprotolithiation
reaction alone or with a concomitant halogen–lithium exchange
furnishing after iodine trapping chiral 4,4′-bipyridines 2 and 6, respectively. The role of n-BuLi in the deprotolithiation process of 1 was elucidated
on the basis of isolated secondary derivatives. After deprotolithiation,
the lithiated species could be trapped by different electrophiles
such as MeI, TMSCl, MeSSMe, R3SnCl (R = Me or n-Bu), and PPh2Cl. Moreover, 4,4′-bipyridine 2 was submitted to cross-coupling reactions (Suzuki and Sonogashira)
which occurred selectively at the carbon–iodine bond. All compounds
of this new family of atropisomeric 4,4′-bipyridines were separated
by chiral HPLC (high-performance liquid chromatography), and the absolute
configurations of obtained enantiomers were mainly assigned by XRD
(X-ray diffraction) using anomalous dispersion.