Chiral Hexahalogenated 4,4'-Bipyridines

Area of Science:

• Organic Chemistry
• Stereochemistry
• Crystallography

Background:

• Chiral 4,4′-bipyridines are valuable ligands and building blocks.
• Developing efficient synthetic routes to diverse isomers is crucial for exploring their properties.

Purpose of the Study:

• To synthesize a library of 27 chiral hexahalogeno-4,4′-bipyridine isomers.
• To develop and compare two complementary synthetic strategies.
• To characterize the synthesized compounds and determine their absolute configurations.

Main Methods:

• Convergent synthesis via LDA-induced dimerization of trihalopyridines.
• Divergent synthesis through regioselective halogenation of 4,4′-bipyridine-2,2′-diones.
• Copper-catalyzed Finkelstein reaction for iodine introduction.
• High-performance liquid chromatography (HPLC) on chiral stationary phases for enantioseparation.
• X-ray diffraction analysis for absolute configuration determination.

Main Results:

• Successful preparation of 27 hexahalogeno-4,4′-bipyridine isomers.
• Demonstration of two distinct synthetic pathways (convergent and divergent).
• Enantioseparation of selected compounds.
• Assignment of absolute configurations and identification of halogen bonding in crystal structures.

Conclusions:

• The developed methods provide access to a diverse range of chiral atropisomeric 4,4′-bipyridines.
• Halogen bonding plays a significant role in the crystal packing of these compounds.
• This work expands the toolkit for synthesizing complex chiral bipyridine derivatives.