Tetrahydrofuran → (Z)-Methyl 5-(1-(3-phenoxyphenyl)-2-oxabicyclo[2.2.2]octan-4-yl)pent-2-enoate

Participants

Reaction Conditions

Reaction Steps

To a solution of bis (2,2,2-trifluoroethyl)(methoxycarbonylmethyl) phosphonate (0.113 mL, 0.535 mmol) and 18-crown-6 (471 mg, 1.78 mmol) in THF (10 mL) at −78° C. was added KHMDS (1.07 mL of a 0.5 M solution in toluene; 0.535 mmol) dropwise. The reaction mixture was stirred at −78° C. for 15 min, and then a solution of 2-(1-(3-phenoxyphenyl)-2-oxabicyclo[2.2.2]octan-4-yl)acetaldehyde (11B compound; 120 mg, 0.357 mmol) in THF (4 mL) was added slowly over 15 min. The reaction mixture was stirred at −78° C. for 30 min and then was quenched with sat. aq. NH4Cl (1 mL), warmed to rt and extracted with EtOAc (3×5 mL). The combined organic extracts were dried (MgSO4) and concentrated in vacuo. The crude oil was purified by flash chromatography on SiO2 (0 to 20% gradient EtOAc:hexanes) to give the title compound (130 mg, 0.331 mmol, 93% yield) as a clear, light yellowish oil. LCMS, [M+H]+=393.2. 1H NMR (CDCl3) δ: 7.38-7.31 (m, 2H), 7.31-7.26 (m, 1H), 7.19-7.13 (m, 2H), 7.12-7.07 (tt, J=7.4, 1.1 Hz, 1H), 7.04-6.98 (m, 2H), 6.89-6.84 (ddd, J=8.0, 2.5, 1.0 Hz, 1H), 6.28-6.20 (dt, J=11.4, 7.5 Hz, 1H), 5.82-5.77 (dt, J=11.3, 1.6 Hz, 1H), 3.85 (s, 2H), 3.74 (s, 3H), 2.69-2.60 (m, 2H), 2.12-1.97 (m, 4H), 1.79-1.65 (m, 4H), 1.35-1.27 (m, 2H);

Provenance & Evidence