Synthetic and mechanistic aspects of the reactions between bromodifluoromethyltriphenylphosphonium bromide and dibromofluoromethyltriphenylphosphonium bromide and trialkylphosphites

Bromofluoromethyltriphenylphosphonium bromides react with trialkylphosphites in two distinct ways. Bromodifluoromethyltriphenylphosphonium bromide undergoes a rapid exchange reaction with trialkylphosphites to give the corresponding bromodifluoromethylphosphonates in good to excellent yields. A similar exchange reaction also occurred with an analogous diethoxyphenylphosphonite to give the corresponding ethoxyphenylphosphinate. Mechanistically, the exchange process involves the formation of difluorocarbene via   dissociation of the intermediate difluoromethylene ylide, capture of the difluorocarbene by the trialkylphosphite to give [(RO)3P+CF2−], which captures bromine followed by dealkylation to the product, bromodifluoromethylphosphonate. The equilibria involved in the multi-step mechanism are all shifted to the phosphonate product by the final dealkylation step. In contrast, the dibromofluoromethyltriphenylphosphonium bromide does not under exchange reactions with trialkylphosphite. The phosphite serves as a halophilic reagent to abstract Br from the dibromofluoromethylphosphonium salt to generate the bromofluoromethylene ylide, which can easily be trapped in situ with aldehydes or ketones to give good yields of the E/Z-bromofluoroalkenes. No dissociation of the bromofluoromethylene ylide was observed.

Bromofluoromethylphenylphosphonium halides react with trialkylphosphites in two distinct ways. Bromodifluoromethyltriphenylphosphonium halides undergo a rapid exchange reaction with trialkylphosphites to give the corresponding bromodifluoromethylphosphonates. A similar exchange reaction also occurred with an analogous dialkoxyphenylphosphonite. Mechanistically, the exchange process involves formation of difluorocarbene via   dissociation of the intermediate difluoromethylene ylide, capture of the difluorocarbene by the trialkylphosphite to give [(RO)3P+CF2−], which captures bromine followed by dealkylation to produce the bromodifluoromethylphosphonate. The equilibria involved in the multi-step mechanism are all shifted to the phosphonate product by the final dealkylation step. This method provides a rapid clean entry to bromodifluoromethylphosphonates or phosphinates from a common intermediate. The yields are equal or better than the Michaelis–Arbuzov methodology [R.W. Vander Haar, D.J. Burton, D.G. Naae, J. Fluorine Chem. 1 (1971/1972) 381–383] and the reaction is especially useful for volatile phosphites due to the mild reaction conditions (RT). In contrast to the bromodifluoromethylphosphonium salt, dibromofluoromethyltriphenylphosphonium bromide does not undergo exchange reactions with trialkylphosphites. The phosphite serves as a halophilic reagent to abstract Br from the dibromofluoromethylphosphonium salt to generate the bromofluoromethylene ylide, which can easily be trapped with aldehhydes or ketones in situ to give E/Z-bromofluoroalkenes. This approach gives yields as good or better than those from R3P/CFBr3 or metal dehalogenation of dibromofluoromethylphosphonium salts [D.J. Burton, Z.-Y. Yang, W. Qiu, Chem. Rev. 96 (1996) 1641–1715; R.W. Vander Haar, D.J. Burton, D.G. Naae, J. Fluorine Chem. 1 (1971/1972) 381–383; R.W. Vander Haar, Ph.D. Thesis, University of Iowa, 1973]. It also avoids the formation of R3PBr2 as a by-product, which can react with aldehyde substrates to decrease the yield of the bromofluoroolefin. It also works well with ketones, such as C6H5C(O)CF2Cl, which reacts readily with Zn or Zn/Cu, again lowering the yield of the olefinic product.Figure optionsDownload as PowerPoint slide