The First α-Fluoroallenylphosphonate, the Synthesis of Conjugated Fluoroenynes, and the Stereoselective Synthesis of Vinylfluorophosphonates Using a New Multifunctional Fluorine-Containing Building Block

Limitations on current methodologies for the introduction of CF2 and CFH in complex α-fluorophosphonates led to the synthesis of a fluorine-containing building block TIPS-C⋮CCFXP(O)(OEt)2, where X = H or F. This multifunctional fluorine synthon reacts with carbonyl compounds under WHE conditions to give high yields of fluorinated conjugated enynes and enediyne. When X = F, trapping of the desilylated anion with an electrophile after TIPS removal provided exclusive access to γ-substituted derivatives of α-fluorophosphonates. When X = H, TBAF deprotection of the silyl group yields H2CCCFP(O)(OEt)2 through an allenyl−propargyl resonance stabilized anion. The allene moiety has been used as template in the stereoselective synthesis of α-fluoro-β,γ-diiodopropenyl phosphonate, via electrophilic iodination, and α-fluoro-γ-amino-α,β-unsaturated phosphonates, including unsaturated phosphononucleosides, by nucleophilic displacement of an allylic iodide. Hydroamination of H2CCCFP(O)(OEt)2 using secondary amines produced (Z)-α-fluoroenaminophosphonates, whereas Diels−Alder cycloaddition with cyclopentadiene provides the corresponding exocyclic vinylfluorophosphonate.