New Selective Haloform-type Reaction Yielding 3-Hydroxy-2,2-difluoroacids:Theoretical Study of the Mechanism

摘要

Experimental results of an unprecedented haloform-type reaction in which 4-alkyl-4-hydroxy-3,3-difluoromethyl trifluoromethyl ketones undergo base-promoted selective cleavage of the CO-CF_3 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-CF_3 bond cleavage in INT leads to a hydrogen-bonded [CH_3CHOHCF_2CO_2H...CF_3]~- complex by passage through a transition structure (TS1) with a DELTAG(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 [CH_3CHOHCF_2CO_2...CHF_3]~- complex.This process has associated with it a DELTAG(298 K) of only 3.1 kcal/ mol and a DELTAG_r(298 K) of -43.3 kcal/mol.The CO-CF_2 bond cleavage in INT leads to a hydrogen-bonded [CH_3CHOHCF_2...CF_3CO_2H]~- complex by passage through a transition structure (TS3) with a DELTAG(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-CF_3 bond cleavage in INT is ascribed to the larger number of fluorine atoms stabilizing the negative charge accumulated on the CF_3 moiety of TS1,as compared to the number of fluorine atoms stabilizing the negative charge on the CH_3CHOHCF_2 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-CF_3 over the CO-CF_2 bond cleavage of R in the gas phase.