ISOLATION AND CHARACTERIZATION OF INTERMEDIATE IN THE SYNTHESIS OF ALPHA-FLUORODIESTERS

The anion [(EtO)(2)P(O)CFCO2Et]Li--(+), pregenerated :from its precurs or diethyl (carboethoxy-fluoromethyl)phosphonate (EtO)(2)P(O)CFHCO2Et and n-butyllithium, was added via syringe to a THF solution of ethyl o xalyl chloride to yield an acylated phosphonate ( EtO)(2)P(O) CF(COCO2 Et)CO2Et. In situ reaction with Grignard reagents RMgX produces the al pha-fluorodiesters (E,Z)-R(CO2Et)C=CFCO2Et in good yields. In contrast , addition of ethyl oxalyl chloride to a THF solution of diethyl (carb oethoxy-fluoromethyl)phosphonate anion gives an isolated intermediate (EtO)(2)P(O)CFCO2Et(CO2Et)C=CFCO2Et. Subsequent reaction of this isola ted intermediate with Grignard reagents also affords a one-pot synthes is of the a-fluorodiesters with high E-stereoselectivity. The E-stereo selectivity increases when HMPT or DMPU is used as a cosolvent in the preparation of diethyl 2-fluoro-3-phenylfumarate (E, Z)-Ph(CO2Et)C=CFC O2Et.