反应详情

The zinc/copper couple was freshly prepared by quickly washing zinc dust with 1N HCl (4×100 mL), then washing with distilled water (4×120 mL), 2 mol % CuSO4 solution (2×200 mL), water (4×120 mL), EtOH (4×120 mL) and Et2O (5×100 mL). The washings were done in a flask with decanting of the liquid. The Et2O washes were poured onto a funnel and dried by vacuum filtration. The resulting solid was added to a 2 L flask and dried under vacuum at 115° C. for 30 min, then cooled to RT. The flask was fitted with an addition funnel and reflux condenser, then purged with nitrogen and kept under N2 throughout the reaction. Next, 400 mL of Et2O was added followed by I2 (0.551 g, 2.172 mmol), and the solution was stirred and heated to reflux. Once at reflux, heating was stopped and diiodomethane (87 mL, 1086 mmol) was slowly added making sure to not allow the reaction to reflux out of control. (2R,3R)-2,3-diphenyl-1,4-dioxaspiro[4.5]dec-6-ene (127 g, 434 mmol) was then added in 350 mL ether, followed by an additional 0.5 eq of diiodomethane. The reaction was heated to reflux and the reaction monitored by LCMS. After 1.5 h the reaction was cooled to RT and quenched with saturated aq Na2CO3 (230 g in 900 mL water). The mixture was stirred for 30 min, then filtered through celite. The inorganics were washed with Et2O (2 L), then the combined organics were washed with saturated aq NH4Cl (1 L), saturated aq NaHCO3 (1 L), brine (1 L). The organic layers were dried over MgSO4, filtered and concentrated to afford the crude product (176.45 g). To the residue was added Et2O (250 mL) and the suspension was heated to reflux, then allowed to cool to RT to crystallize the product. The suspension was put in the freezer for 3 days, then the ether decanted off. Drying of the solids gave (1S,4′R,5′R,6R)-4′,5′-diphenylspiro[bicyclo[4.1.0]heptane-2,2′-[1,3]dioxolane] (112.5 g, 85% yield). The material was used as an intermediate without further purification.

1. washwashing with distilled water (4×120 mL), 2 mol % CuSO4 solution (2×200 mL), water (4×120 mL), EtOH (4×120 mL) and Et2O (5×100 mL)
2. customThe washings were done in a flask
3. customwith decanting of the liquid
4. additionThe Et2O washes were poured onto a funnel
5. customdried by vacuum filtration
6. additionThe resulting solid was added to a 2 L flask
7. customdried under vacuum at 115° C. for 30 min
8. customThe flask was fitted with an addition funnel
9. temperaturereflux condenser
10. custompurged with nitrogen
11. customkept under N2 throughout the reaction
12. temperatureheated to reflux
13. temperatureOnce at reflux
14. temperatureheating
15. customthe reaction
16. temperatureto reflux out of control
17. temperatureThe reaction was heated
18. temperatureto reflux
19. temperatureAfter 1.5 h the reaction was cooled to RT
20. customquenched with saturated aq Na2CO3 (230 g in 900 mL water)
21. stirringThe mixture was stirred for 30 min
22. filtrationfiltered through celite
23. washThe inorganics were washed with Et2O (2 L)
24. washthe combined organics were washed with saturated aq NH4Cl (1 L), saturated aq NaHCO3 (1 L), brine (1 L)
25. dry with materialThe organic layers were dried over MgSO4
26. filtrationfiltered
27. concentrationconcentrated
28. customto afford the crude product (176.45 g)
29. temperaturethe suspension was heated
30. temperatureto reflux
31. temperatureto cool to RT
32. customto crystallize the product
33. customthe ether decanted off
34. customDrying of the solids