Propanoic acid, 2-[bis(2,2,2-trifluoroethoxy)phosphinyl]-, methyl ester

The Uses of Propanoic acid, 2-[bis(2,2,2-trifluoroethoxy)phosphinyl]-, methyl ester

Methyl 2-[Bis(2,2,2-trifluoroethoxy)phosphinyl]propionate is synthetic reagent used in Z-selective HWE reactions (a.k.a. Still-Genari modification) to make alpha,β-unsaturated esters. Methyl 2-[Bis(2,2,2-trifluoroethoxy)phosphinyl]propionate is used as reagent/reactant for preparation of (±)-(Z)-2β-hydroxy-14-hydro-β-santalol via tandem radical cyclization.

Synthesis

KHMDS (8.0 mL, 4.00 mmol, 0.5M in toluene) was added by syringe to a solution of dried 18-crown-6 (4.20 g, 15.89 mmol), THF (20 mL), and Bis (2,2,2-trifluoroethyl) phosphite  (0.55 mL, 3.75 mmol) at -78 ℃. Following 15 min, methyl 2-bromopropionate (0.35 mL, 3.14 mmol) was added to the reaction flask. The reaction mixture was allowed to warm to room temperature for 4hr. The standard workup protocol was followed, then the crude product was purified by flash column chromatography (9:1-3:2 hexanes:EtOAc, Rf = 0.22 in 1:1 hexanes:EtOAc) yielding Propanoic acid, 2-[bis(2,2,2-trifluoroethoxy)phosphinyl]-, methyl ester (103 mg, 31 mmol, 9.9%) as a yellow syrup.