A new approach to the synthesis of (Z)-2-fluoro-2-alkenals via Wittig-type carbonyl condensation reactions of 2-(fluoromethyl)-4,4,6-trimethyl-1,3-oxazine phosphonium bromide

We report here the transformation of aldehydes to their (Z)-α-fluoro-α,β-unsaturated aldehyde homologs by condensation with the phosphonium salt of the Meyer’s oxazine obtained from bromofluoroacetonitrile. After methylation with trimethyloxonium tetrafluoroborate the quaternized oxazine is cleanly reduced to mostly Z 2-fluoro-2-alkenals by sodium borohydride at room temperature. This methodology is compatible with usual protecting groups and affords an efficient access to functionalized mostly Z 2-fluoro-2-alkenals derived from natural products and their corresponding (Z)-2-fluoro-2-alkenols.