Typical procedure for the HWE reaction of bis-(2,2,2-trifluoroethyl)phosphonoacetic acid (4) with i-PrMgBr
A 0.76M solution of i-PrMgBr (1.96 mL, 1.49 mmol) in THF was added to a stirred solution of bis-(2,2,2-trifluoroethyl)phosphonoacetic acid (4) (218 mg, 0.72 mmol) in anhydrous toluene (10 mL) at 0 °C under argon. The mixture was stirred at 0°C for 1 h and then heated at reflux. 3- Phenylpropionaldehyde (7a) (80 µL, 0.60 mmol) was added to the refluxing solution. After being heated at reflux for 1 h, the reaction mixture was treated with 5% HCl and then extracted with AcOEt (70 mL x3). The extract was submitted to the usual workup to afford a crude product 8a (E:Z = 95:5). To the solution of 8a in MeOH (2 mL) and benzene (7 mL) was added an excess amount of TMSCHN2 (2.0M solution in n-hexane, ca. 1 mL, ca. 2 mmol). After being stirred at room temperature for 30 min, the reaction mixture was evaporated in vacuo to afford a crude product, which was purified by chromatography on a silica gel (Kanto Chemical N60) column [n-hexane/AcOEt/acetone (50:2:1)] to afford (E)-9a (89 mg, 78%) and (Z)-9a (4.7 mg, 4%) as colorless oils.
Methyl (E)-5-phenyl-2-pentenoate [(E)-9a].2b,10 Colorless oil; 1H NMR (400 MHz, CDCl3) d 2.48–2.57 (2H, m), 2.77 (2H, t, J = 7.7 Hz), 3.72 (3H, s), 5.85 (1H, td, J = 1.5, 15.6 Hz), 7.01 (1H, td, J = 6.8, 15.6 Hz), 7.16–7.24 (3H, m), 7.24–7.32 (2H, m); 13C NMR (75 MHz, CDCl3) d 33.9, 34.3, 51.4, 121.4, 126.2, 128.3, 128.5, 140.7, 148.4, 167.0.
Methyl (Z)-5-phenyl-2-pentenoate [(Z)-9a].2b,10 Colorless oil; 1H NMR (400 MHz, CDCl3) d 2.77 (2H, t, J = 7.6 Hz), 2.96–3.03 (2H, m), 3.70 (3H, s), 5.79 (1H, td, J = 1.5, 11.5 Hz), 6.25 (1H, td, J = 7.4, 11.5 Hz), 7.16–7.32 (5H, m); 13C NMR (75 MHz, CDCl3) d 30.5, 35.0, 51.1, 119.9, 126.0, 128.4, 128.5, 141.1, 149.4, 166.7.
Methyl (E)-3-phenyl-2-propenoate [(E)-9b].2b,11 Colorless plates (n-hexane), mp 32.5–33 °C (lit.10a 34–34.5 °C); 1H NMR (400 MHz, CDCl3) d 3.81 (3H, s), 6.44 (1H, d, J = 16.0 Hz), 7.36– 7.42 (3H, m), 7.50–7.56 (2H, m), 7.70 (1H, d, J = 16.0 Hz); 13C NMR (75 MHz, CDCl3) d 51.7, 117.8, 128.1, 128.9 130.3, 134.4, 144.9, 167.4.
Methyl (2E,4E)-5-phenyl-2,4-pentadienoate [(E)-9c].12 White powder (Et2O–n-hexane), mp 71 °C (lit.11b 68–70 °C); 1H NMR (400 MHz, CDCl3) d 3.78 (3H, s), 6.00 (1H, d, J = 15.4 Hz), 6.83–6.95 (2H, m), 7.28–7.40 (3H, m), 7.42–7.50 (3H, m); 13C NMR (75 MHz, CDCl3) d 51.6, 120.8, 126.2, 127.2, 128.8, 129.1, 136.0, 140.5, 144.8, 167.5.
Methyl (2Z,4E)-5-phenyl-2,4-pentadienoate [(Z)-9c].12a Colorless oil; 1H NMR (400 MHz, CDCl3) d 3.77 (3H, s), 5.74 (1H, d, J = 11.0 Hz), 6.71–6.80 (1H, m), 6.83 (1H, d, J = 15.6 Hz), 7.27–7.39 (3H, m), 7.50–7.56 (2H, m), 8.14 (1H, dd, J = 11.5, 15.6 Hz); 13C NMR (75 MHz, CDCl3) d 51.2, 116.9, 124.8, 127.5, 128.7, 129.0, 136.3, 141.4, 145.0, 167.0.
Methyl (E)-3-cyclohexyl-2-propenoate [(E)-9d].13a,b Colorless oil; 1H NMR (400 MHz, CDCl3) d 1.07–1.38 (5H, m), 1.62–1.82 (5H, m), 2.08–2.20 (1H, m), 3.73 (3H, s), 5.77 (1H, dd, J = 1.3, 15.9 Hz), 6.92 (1H, dd, J = 6.8, 15.9 Hz); 13C NMR (75 MHz, CDCl3) d 25.7, 25.9, 31.7, 40.4, 51.4, 118.5, 154.7, 167.6.
Methyl (Z)-3-cyclohexyl-2-propenoate [(Z)-9d].13c Colorless oil; 1H NMR (400 MHz, CDCl3) d 1.02–1.42 (5H, m), 1.65–1.76 (5H, m), 3.24–3.36 (1H, m), 3.70 (3H, s), 5.67 (1H, J = 11.4
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