Synthetic application of fluorinated vinamidinium salts: Synthesis of fluorinated 1,3-butadienylphosphonates by the reaction with Horner–Wadsworth–Emmons reagents

The reaction of β-fluoro vinamidinium salt 1 with Horner–Wadsworth–Emmons reagents (HWE) such as diethyl(ethoxycarbonyl)methylphosphonate (2a), diethyl(methoxycarbonyl)methylphosphonate (2b), diethyl-2-oxopropylphosphonate (2c), diethyl benzylphosphonate (2d), tetraethyl methylenediphosphonate (2e) and diethyl cyanomethylphosphonate (2f) under basic conditions gave the fluorinated 1,3-butadienylphosphonates 3 in moderate to good yields. The phosphonates 3 could be hydrolyzed with a 10% HCl aqueous solution to afford the corresponding γ-(diethylphosphono)-α-fluoro-α,β-unsaturated aldehydes 7 in good yields. The treatment of the phosphonate 3c with an NH3 aqueous solution at 70 °C produced the pyridine derivative 8 in 60% yield.

Graphical abstractThe reaction of β-fluoro vinamidinium salt with Horner–Wadsworth–Emmons reagents gave the fluorinated 1,3-butadienylphosphonates in moderate to good yields, which could be hydrolyzed with a 10% HCl aqueous solution to afford the corresponding γ-(diethylphosphono)-α-fluoro-α,β-unsaturated aldehydes in good yields. The treatment of the phosphonate, derived from the reaction of vinamidinium salt with diethyl-2-oxopropylphosphonate, with an NH3 aqueous solution at 70 °C produced the pyridine derivative in 60% yield.Figure optionsDownload full-size imageDownload as PowerPoint slide