Synthetic and mechanistic aspects of halo-F-methylphosphonates

The synthesis of a variety of new halo-F-methylphosphonates has been achieved by a Michaelis–Arbuzov type reaction between a halo-F-methane and a trialkyl phosphite. This synthesis has proved to be of wide scope and utility for the high yield preparation of a number of heretofore unknown compounds. The 1H, 19F, 13C and 31P NMR spectroscopic properties are reported in detail. The mechanism for the formation of bromodifluoromethylphosphonates has been shown to proceed through the intermediacy of difluorocarbene:CF2. The phosphonate products have been shown to react with a wide variety of reagents. Fluoride and alkoxide ions react by attack at phosphorus with cleavage of the carbon–phosphorus bond and formation of [:CF2] from the bromodifluoromethylphosphonates and the CFBr2− anion from the dibromofluoromethylphosphonates. Iodide ion and tertiary phosphines react by attack at the ester carbon to give stable phosphonate salts. Hydrolysis of the phosphonate esters with 50% aqueous HCl gives the expected phosphonic acids. Trimethylsilyl bromide attacks phosphoryl oxygen to afford the bis(trimethylsilyl) esters.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Trialkylphosphites react with halo-F-methanes to afford halo-F-methylphosphonates. ► Mechanistically, the reaction involves halophilic attack on the halo-F-methane. ► Difluorocarbene is the reaction intermediate with CF2Br2, CF2BrI, and CF2BrCl. ► CFBr2− ion is the reaction intermediate with CFBr3. ► Various reagents attack all sites of the phosphonate except the CF2 group.