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

Abstract

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_as predicted by DFT methods. Extensive DFT calculations have been used to rationalize the selective formation of four out of nine possible F₂Cl_1-4 isomers of bridge-halogenated bicyclo[1.1.1]pentanes and to obtain relative strain energies for all possible isomers.