We report defluorinative and deoxygenative functionalization reactions of trifluoromethyl ketones mediated by the phospha-Brook rearrangement, offering a streamlined approach to selectively modifying fluorinated compounds. Trifluoromethyl ketones react with phosphine oxides to undergo a phospha-Brook rearrangement followed by β-fluoride elimination, providing difluoromethyl ketones in good yields. By tuning the reaction conditions, we achieved the selective one-pot synthesis of monofluoromethyl ketones and methyl ketones, demonstrating the method’s versatility across a range of fluorine-containing derivatives. Furthermore, we successfully demonstrated a range of deoxygenative transformations of key intermediates, such as difluoroenol phosphinates, showcasing their potential as building blocks for diverse functionalizations. These findings not only expand the synthetic toolbox for fluorine-containing molecules but also highlight the utility of phosphonate intermediates in developing novel reaction pathway.
