Bis(2,2,2-trifluoroethyl) (Methoxycarbonylmethyl)phosphonate

Used Chemicals

• p-Tolualdehyde [T1073]
• Bis(2,2,2-trifluoroethyl) (Methoxycarbonylmethyl)phosphonate [B1714]
• Potassium tert-Butoxide [P1008]
• 18-Crown 6-Ether [C0860]
• THF

Procedure

Potassium tert-butoxide (236 mg, 2.1 mmol, 2.1 eq.) in dry THF (5 mL) was added dropwise to the solution of p-tolualdehyde (120 mg, 1.0 mmol), bis(2,2,2-trifluoroethyl) (methoxycarbonylmethyl)phosphonate (636 mg, 2.0 mmol, 2.0 eq.) and 18-crown-6-ether (793 mg, 3.0 mmol, 3.0 eq.) in dry THF (5 mL) at -78 °C. The mixture was stirred for 2 hours. Then the mixture was stirred at r.t. for overnight and quenched with water (15 mL). The aqueous layer was extracted with ethyl acetate (15 mL x 3) and the combined organic layer was washed with 2 mol/L HCl aq. (10 mL), sat. NaHCO₃ aq. (10 mL), and brine (10 mL), dried over sodium sulfate and filtered. The solvent was removed under reduced pressure and the residue was purified by column chromatography (on silica gel, toluene:diethyl ether = 40:1) to give 1 as a pale yellow liquid (138 mg, 78% yield, E:Z = 1:15.5).

Experimenter’s Comments

The reaction mixture was monitored by UPLC.
The ratio of E form and Z form was estimated from NMR.

Analytical Data

Compound 1

¹H NMR (400 MHz, CDCl₃);
1-Z: δ 7.53 (d, J = 7.6 Hz, 2H), 7.17 (d, J = 7.6 Hz, 2H), 6.91 (d, J = 12.8 Hz, 1H), 5.90 (d, J = 12.8 Hz, 1H), 3.72 (s, 3H), 2.36 (s, 3H).
1-E: δ 7.67 (d, J = 16.0 Hz, 1H), 7.42 (d, J = 8.4 Hz, 2H), 7.20 (d, J = 8.4 Hz, 2H), 6.40 (d, J = 16.0 Hz, 1H), 3.80 (s, 3H), 2.37 (s, 3H).

Lead Reference

• Direct synthesis of Z-unsaturated esters. A useful modification of the horner-emmons olefination.
• W. C. Still, C. Gennari, Tetrahedron Lett. 1983, 24, 4405.

Direct synthesis of Z-unsaturated esters

W. C. Still, C. Gennari, Tetrahedron Lett. 1983, 24, 4405.S. J. Danishefsky, M. P. DeNinno, J. Org. Chem. 1986, 51, 2615.W. R. Roush, A. D. Palkowitz, ibid. 1989, 54, 3009.

S. J. Danishefsky, M. P. DeNinno, J. Org. Chem. 1986, 51, 2615.

W. R. Roush, A. D. Palkowitz, ibid. 1989, 54, 3009.

α-Alkylation of reagent B1714 and olefination

J. C. Medina, R. Guajardo, K. S. Kyler, J. Am. Chem. Soc. 1989, 111, 2310.