Structural and kinetic considerations for the application of the traceless Staudinger ligation to future 18F radiolabeling using XRD and 19F-NMR

A 4-fluorobenzoate-functionalized phosphane was synthesized and reacted with different azides using the traceless Staudinger ligation as a representative sample reaction for future radiolabeling purposes with short-lived radionuclides like fluorine-18. For this purpose, the reaction rate was evaluated at different temperatures. The effect of starting material concentrations and the influence of the steric effect coming from the applied azides were investigated. 19F NMR was used to determine the reaction half-live (τ1/2) and the reaction rate constant (kobs) of this ligation under mild reaction conditions in a water–acetonitrile mixture. Furthermore, the phosphane key compound 1 (orthorhombic, space group Pna21, a = 18.6363(9), b = 8.3589(4), c = 18.5480(9) Å, V = 2889.4(2) Å3, Z = 8, Dobs = 1.277 g/cm3), which acts as starting material for all subsequent syntheses, and the fluorine-containing phosphane 3 (monoclinic, space group P21/c, a = 8.321(2), b = 16.160(4), c = 14.940(4) Å, β = 99.51(1)°, V = 1981.4(8) Å3, Z = 4, Dobs = 1.342 g/cm3) were analyzed by single-crystal XRD.