64% |
Stage #1: 3,4,5,6-tetrahydro-2H-pyran-2-one With diisobutylaluminium hydride In tetrahydrofuran; toluene at -78℃; for 1.5h; Sealed tube; Inert atmosphere;
Stage #2: Methyl diethylphosphonoacetate With n-butyllithium In tetrahydrofuran; toluene at -78 - 20℃; for 24h; Sealed tube; Inert atmosphere; |
3 Methyl (E)-7-hydroxyhept-2-enoate (E)-1b
In a round bottom flask, 3.0 g of δ-valerolactone (100.0 g/mol; 30 mmol) was dissolved in 10 mL of dry THF. The flask was sealed, purged with Ar, and cooled to -78 °C in a CO2-acetone bath. Next 24 mL of DIBAL-H (diisobutylaluminum hydride, CAS: 1191-15-7, 142.2 g/mol, 36 mmol, 1.5 M toluene solution) were added and the reaction was magnetically stirred for 90 min. In a pear-shaped flask, 7.56 g of methyl diethylphosphonoacetate (CAS: 1067-74-9, 210.1 g/mol, 0.036 mmol) was dissolved in 24 mL of dry THF. This flask was sealed, purged with Ar and cooled at -78 °C. Next, 22.5 mL of nBuLi (n-butyllithium, CAS: 109-72-8, 64.1 g/mol, 45 mmol) was added, turning the solution yellowish. The solution was stirred 15 min at -78 °C, then warmed to 0 °C in an ice bath for 30 min and finally to -78 °C for 15 min. The yellowish solution was added dropwise over the reaction mixture. Once the addition was finished, the resulting mixture was magnetically stirred for 4 h at -78 °C. Then, the flask was allowed to warm to room temperature and stirred for 20 h more. Finally, the reaction was quenched with a saturated solution of sodium-potassium tartrate. 60 min later, the reaction mixture was extracted with AcOEt (3 times). The organic layers were combined and washed with satd NaHCO3 (3 times) and brine (1 time). The AcOEt washed solution was dried with anhydrous Na2SO4, filtered, and the solvent was removed under reduced pressure. Flash chromatography afforded 1.509 g of ester 1b (Hexanes/AcOEt 98:2, 64% yield). Rf = 0.46 (Hexanes/AcOEt, 1:1); IR (neat): νmax = 3367 (O-H), 2937 (C-H), 1718 (C=O), 1436, 1201 (C-O) cm-1; 1H NMR (200 MHz, CDCl3): δ = 6.95 (dt, J = 15.5 and 6.8 Hz, 1H, H-3), 5.81 (d, J = 15.7 Hz, 1H, H-2), 3.70 (s, 1H, CO2CH3), 3.63 (t, J = 5.7 Hz, 2H, H-7), 2.22 (q, J = 6.7 Hz, 2H, H-4), 1.87 (br s, 1H, OH), 1.60-1.52 (4H, H-5 and H-6) ppm; 13C NMR (50 MHz, CDCl3): δ = 167.3 (s, C-1), 149.5 (d, C-3), 121.2 (d, C-2), 62.4 (t, C-7), 51.6 (s, CO2CH3), 32.2 (t, C-6), 32.0 (t, C-4), 24.4 (t, C-5) ppm; HRMS (ESI): m/z (M+Na) calcd for C8H14O3Na, 181.0835; found, 181.0840, Δ = -2.76 ppm. |