Polyhalogenated Bicyclo[1.1.1]pentane-1,3-dicarboxylic Acids

Herein we report the highly selective
radical chlorination of 2,2-difluorobicyclo[1.1.1]­pentane-1,3-dicarboxylic
acid. Together with radical hydrodechlorination by TMS3SiH, four new bicyclo[1.1.1]­pentane cages carrying two fluorine and
one to three chlorine atoms in bridge positions have been obtained.
The exact positions of all halogen atoms have been confirmed by X-ray
diffraction. The acidity constants (pKa) for all new derivatives have been determined by capillary electrophoresis,
and these experimental values show excellent agreement with pKas predicted by DFT methods. Extensive DFT calculations
have been used to rationalize the selective formation of four out
of nine possible F2Cl1–4 isomers of bridge-halogenated
bicyclo[1.1.1]­pentanes and to obtain relative strain energies for
all possible isomers.