Isolation and Characterization of intermediate in the Synthesis of α-Fluorodiesters

The anion [(EtO)₂P(O)CFCO₂Et]^?Li⁺, pregenerated from its precursor diethyl (carboethoxyfluoromethyl)phosphonate (EtO)₂P(O)CFHCO₂Et and n-butyllithium, was added via syringe to a THF solution of ethyl oxaiyl chloride to yield an acylated phosphonate (EtO)₂P(O)CF(COCO₂Et)CO₂Et. In situ reaction with Grignard reagents RMgX produces the α-fluorodiesters (E,Z)-R(CO₂Et)C=CFCO₂Et in good yields. In contrast, addition of ethyl oxalyl chloride to a THF solution of diethyl (carboethoxyfluoromethyl)phosphonate anion gives an isolated intermediate (EtO)₂P(O)CFCO₂Et(CO₂Et)C=CFCO₂Et. Subsequent reaction of this isolated intermediate with Grignard reagents also affords a one-pot synthesis of the α-fluorodiesters with high E-stereoselectivity. The E-stereoselectivity increases when HMPT or DMPU is used as a cosolvent in the preparation of diethyl 2-fluoro-3-phenylfumarate (E,Z)-Ph(CO₂Et)C=CFCO₂Et.