Chemoselective halogenation of 2-hydroperfluoroalkyl aldehydes

2-Hydroaldehydes, RfCH(R)CHO, where Rf = CF3, C2F5, n-C3F7 and R = CF3, C2F5, n-C3F7, Ph, H, were prepared via acid hydrolysis of the corresponding vinyl ethers, RfC(R) = CHOCH3, which can be readily prepared by reaction of [Ph3P+C¯HOCH3] with the corresponding ketone. The 2-hydroaldehydes can be chemoselectively converted to the acyl halide, RfCH(R)C(O)X (X = Cl, Br), via free-radical halogenation. The perfluoroalkyl group deactivates the 2-position toward radical abstraction of the 2-hydrogen, and halogenation occurs exclusively at the formyl hydrogen. However, halogenations of the 2-hydroaldehydes in glacial acetic acid chemoselectively gives the 2-haloaldehydes, RfCX(R)CHO, X = Cl, Br. Hydrolysis of the 2-hydroperfluoroacyl halides provides a useful route to 2-hydroperfluoroalkyl branched carboxylic acids, useful ketene precursors. This route avoids the use of toxic fluoroolefins, such as perfluoroisobutylene.

Graphical abstractFree-radical chlorination or bromination of 2-hydroperfluoroalkyl aldehydes chemoselectively affords the corresponding acyl halide. Only the formyl hydrogen is replaced by halogen. However, in a polar solvent, such as acetic acid, chlorination or bromination of 2-hydroperfluoroalkyl aldehydes affords only the 2-haloperfluoroalkyl aldehydes. Hydrolysis of the 2-hydroperfluoacyl halides provides a useful, convenient, non-toxic entry to the corresponding 2-hydroperfluoroalkyl branched carboxylic acids. The requisite 2-hydroperfluoroalkyl aldehydes are conveniently prepared via   reaction of a perfluoroalkyl ketone with Ph3P+C¯HOCH3, followed by acid hydrolysis of the perfluoroalkyl vinyl ethers.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Chemoselective free-radical halogenation of 2-hydroperfluoro aldehydes. ► Direct conversion of 2-hydroperfluoroalkyl aldehydes to acyl halides. ► Conversion of 2-hydroperfluoroalkyl aldehydes to 2-haloperfluoroalkyl aldehydes. ► Preparation of 2-hydroperfluoroalkyl branched carboxylic acids. ► Preparation of 2-hydroperfluoroalkyl aldehydes from perfluoroalkyl ketones.