反应详情

To a stirred suspension of Zn (0.59 g, 9.00 mmol) in THF (10 mL) was added TiCl4 (0.50 mL, 4.50 mmol) dropwise. The mixture was refluxed under nitrogen for 2.5 h. After cooling to room temperature, a solution of 61 (0.34 g, 1.12 mmol) and 3,3,5,5-tetramethylcyclohexanone (0.53 g, 3.37 mmol) in THF (15 mL) was added and the reaction mixture refluxed for an additional 2.5 h. Cooled to room temperature, the reaction was quenched with 10% K2CO3 (20 mL). The quenched reaction mixture was filtered through a pad of Celite and the pad was washed with EtOAc (100 mL). The filtrate was transferred to a separatory funnel, the layers were separated, and the aqueous phase was extracted with EtOAc (50 mL). The combined organic extracts were washed with brine, dried (Na2SO4) and concentrated to give a pale yellow oil. The residue was further purified by chromatography on a silica gel column eluted with a gradient from hexanes to 55% EtOAc:hexanes to give 62 as a white solid (0.36 g, 75%). mp 122-124° C. 1H NMR (400 MHz, CD3OD): δ 0.91 (s, 6H), 0.92 (s, 6H), 1.28 (s, 2H), 1.96 (s, 2H), 1.98 (s, 2H), 3.60-3.65 (m, 2H), 3.65-3.70 (m, 2H), 3.80-3.85 (m, 2H), 4.05-4.15 (m, 2H), 6.67 (d, J=8.4 Hz, 2H), 6.83 (d, J=8.6 Hz, 2H), 6.94 (d, J=8.6 Hz, 2H), 7.03 (d, J=8.6 Hz, 2H). LRMS (APCI): m/z 425 (M+H)+, 423 (M−H)−. Anal. Calcd for C27H36O4: C, 76.38; H, 8.55; Found: C, 76.17; H, 8.65.

1. temperatureThe mixture was refluxed under nitrogen for 2.5 h
2. temperaturethe reaction mixture refluxed for an additional 2.5 h
3. temperatureCooled to room temperature
4. customthe reaction was quenched with 10% K2CO3 (20 mL)
5. customThe quenched reaction mixture
6. filtrationwas filtered through a pad of Celite
7. washthe pad was washed with EtOAc (100 mL)
8. customThe filtrate was transferred to a separatory funnel
9. customthe layers were separated
10. extractionthe aqueous phase was extracted with EtOAc (50 mL)
11. washThe combined organic extracts were washed with brine
12. dry with materialdried (Na2SO4)
13. concentrationconcentrated
14. customto give a pale yellow oil
15. customThe residue was further purified by chromatography on a silica gel column
16. washeluted with a gradient from hexanes to 55% EtOAc