Cuprous chloride promoted coupling reaction of diethoxyphosphinyldifluoromethylcadmium reagent with aryl iodides: A practical and convenient preparation of α,α-difluoro benzylic phosphonates

Diethylbromodifluoromethylphosphonate reacts with cadmium powder in situ in DMF to form diethoxyphosphinyldifluoromethylcadmium, which is then treated with CuCl to give the corresponding copper reagent. The copper reagent is then reacted in situ with substituted aryl iodides to give excellent yields of α,α-difluoro benzylic phosphonates. This method is also applicable to the synthesis of bis α,α-difluoro benzylic phosphonates. All the reactions are conducted at room temperature, and all intermediates are formed in situ. No low temperature reactions are involved; no prior formation of a hydrocarbon phosphonate is required and no expensive electrophilic fluorinating agents are required. Many functional groups such as NO2, hydrogen, chlorine, OMe carboxylic acid esters, phenyl, CF3, CH3 are tolerated in reaction sequence. Substituted pyridine, thiophene and pentafluoro phenyl derivatives also react well.