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 (pK(a)) for all new derivatives have been determined by capillary electrophoresis, and these experimental values show excellent agreement with pK(a)s 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.

Automated summary

Highly selective radical chlorination of 2,2-difluorobicyclo[1.1.1]pentane-1,3-dicarboxylic acid was reported, resulting in new bicyclo[1.1.1]pentane cages carrying fluorine and chlorine atoms. The positions of halogen atoms and acidity constants were confirmed by X-ray diffraction and capillary electrophoresis, respectively, with experimental values in agreement with those predicted by DFT methods. Extensive DFT calculations were used to rationalize the selective formation of isomers and determine relative strain energies.