Experimental results of an unprecedented haloform-type reaction in which 4-alkyl-4-hydroxy3,3-difluoromethyl trifluoromethyl ketones undergo base-promoted selective cleavage of the CO-CF3 bond, yielding 3-hydroxy-2,2-difluoroacids and fluoroform, are rationalized using DFT (B3LYP) calculations. The gas-phase addition of hydroxide ion to 1,1,1,3,3-pentafluoro-4-hydroxypentan-2-one (R) is found to be a barrierless process, yielding a tetrahedral intermediate (INT), involving a DeltaG(r)(298 K) of -61.4 kcal/mol. The CO-CF3 bond cleavage in INT leads to a hydrogen-bonded [CH3CHOHCF2CO2H...CF3](-) complex by passage through a transition structure (TS1) with a DeltaG(double dagger)(298 K) of 20.8 kcal/mol and a DeltaG(r)(298 K) of 9.8 kcal/mol. This complex undergoes a proton transfer between its components, yielding a hydrogen-bonded [CH3CHOHCF2CO2...CHF3](-) complex. This process has associated with it a DeltaG(double dagger)(298 K) of only 3.1 kcal/mol and a DeltaG(r)(298 K) of -43.3 kcal/mol. The CO-CF2 bond cleavage in INT leads to a hydrogen-bonded [CH3CHOHCF2...CF3CO2H](-) complex by passage through a transition structure (TS3) with a DeltaG(double dagger)(298 K) of 29.2 kcal/mol and a DeltaG(r)(298 K) of 25.1 kcal/mol. The lower energy barrier found for CO-CF3 bond cleavage in INT is ascribed to the larger number of fluorine atoms stabilizing the negative charge accumulated on the CF3 moiety of TS1, as compared to the number of fluorine atoms stabilizing the negative charge on the CH3CHOHCF2 moiety of TS3. The solvent-induced effects on the two pathways, introduced within the SCRF formalism through PCM calculations, do not reverse the predicted preference of the CO-CF3 over the CO-CF2 bond cleavage of R in the gas phase.