One-Pot Reaction of (β-Amino-α,α-difluoroethyl)phosphonates with Trifluoromethylated Ketones via Aza-Wittig Reagents

We report a one-pot reaction of (beta-amino-alpha,alpha-difluoroethyl)phosphonates involving aza-Wittig reagents, in which, difluoromethylphosphonate-containing diazo and trifluoromethylated ketones assemble to furnish azo-containing alpha-fluorovinylphosphonates. Mechanism studies disclose a pathway, which contains an aza-Wittig reaction, water addition to hydrazone, and C-F bond cleavage with an aza-Wittig reagent as a key intermediate. This reaction is conducted at 60 degrees C affording a series of alpha-fluorovinylphosphonate compounds in 42-94% yields and Z-stereoselectivity. This work opens a vision for the difluoroalkyl-substituted diazos, and provides a strategy for the synthesis of alpha-fluorovinylphosphonate derivatives.