反应详情

To an ice water cooled stirred suspension of (methoxymethyl)triphenylphosphonium chloride (17 g, 49.57 mmol) in anhydrous THF (100 mL) under nitrogen was added lithium bis(trimethylsilyl)amide (1M solution in THF; 50 mL, 50 mmol), and the reaction mixture was allowed to stir at 0° C. for 30 mins. 1-Phenylbicyclo[2.2.2]octane-4-carbaldehyde (Intermediate 6; 10.52 g, 49.08 mmol) in THF (20 mL) was added dropwise and the reaction mixture was allowed to stir at 0° C. for one hour and then at ambient temperature overnight. Water (100 mL) was added and the reaction mixture was partitioned between EtOAc (200 mL) and brine (100 mL), the organic phase was washed with an additional 100 mL of brine then separated, dried (MgSO4) and concentrated to leave a pale yellow gum. The residue was purified on a 330 g Presearch silica cartridge, loading in isohexane/DCM and eluting 0-20% EtOAc-isohexane to provide the title compound as a pale yellow oil (12.6 g, 50.19 mmol, 100%) as a 1:2 mixture of E:Z isomers; E isomer 1H NMR (CDCl3) δ 1.60-1.65 (2H, m), 1.82-1.88 (10H, m), 3.49 (3H, s), 4.74 (1H, d), 6.18 (1H, d), 7.12-7.18 (1H, m), 7.25-7.34 (4H, m); Z isomer: 1H NMR (CDCl3) δ 1.60-1.65 (2H, m), 1.82-1.88 (10H, m), 3.54 (3H, s), 4.09 (1H, d), 5.71 (1H, d), 7.12-7.18 (1H, m), 7.25-7.34 (4H, m); MS (same for both individual isomers): GC-MS EI+ m/e 242 (M+).

1. stirringto stir at 0° C. for 30 mins
2. stirringto stir at 0° C. for one hour
3. customat ambient temperature
4. customovernight
5. customthe reaction mixture was partitioned between EtOAc (200 mL) and brine (100 mL)
6. washthe organic phase was washed with an additional 100 mL of brine
7. customthen separated
8. dry with materialdried (MgSO4)
9. concentrationconcentrated
10. customto leave a pale yellow gum
11. customThe residue was purified on a 330 g Presearch silica cartridge, loading in isohexane/DCM
12. washeluting 0-20% EtOAc-isohexane