反应详情

温度

-78 °C

To a 40-mL scintillation vial equipped with a magnetic stir bar was added 1-(biphenyl-2-yl)-2,2,6,6-tetramethylphosphinan-4-one (900 mg, 2.77 mmol, 1 equiv). The vial was sealed with a septa-top cap and then purged with nitrogen gas for 10 minutes. The solid was then dissolved with anhydrous, degassed dichloromethane (9 mL). In a separate 250-mL round bottom flask was added anhydrous, degassed dichloromethane (31 mL) which was cooled to −78° C. Boron trifluoride diethyl etherate (527 μL, 4.16 mmol, 1.5 equiv) was then added to the flask. The phosphine solution was transferred by cannula to the reaction flask over the course of 3 minutes using a positive pressure of nitrogen gas. After stirring the solution for 5 minutes, (trimethylsilyl)diazomethane (2.1 mL, 4.16 mmol, 1.5 equiv, 2 M in hexane) was added slowly over 3 minutes The bright yellow solution was stirred at −78° C. for an hour, and then diluted with 1 M aqueous hydrochloric acid (50 mL). The slurry was warmed to room temperature overnight. The solution was charged into a separatory funnel and the phases were partitioned. The dichloromethane layer was collected, and the aqueous layer was washed with dichloromethane (3×20 mL). The combined organic layers were then washed with aqueous saturated sodium bicarbonate (50 mL), dried over sodium sulfate, filtered, and concentrated in a rotary evaporator. Purification of the crude product oil by silica gel column chromatography on an Isco CombiFlash system (120-g column; gradient: 1.5 column volumes heptane, ramp up to 98:2 heptane:methyl tert-butyl ether over 0.5 column volumes, hold at 98:2 for 2 column volumes, ramp up to 75:25 heptane:methyl tert-butyl ether over 8 column volumes, hold at 75:25 for 2 column volumes) afforded the title compound as a white solid (578 mg, 98 area % by HPLC, 62% yield). 1H NMR (400 MHz, CDCl3) δ ppm 7.88 (dt, J=7.8, 1.5 Hz, 1H), 7.47-7.32 (m, 5H), 7.32-7.27 (m, 1H), 7.26-7.20 (m, 2H), 2.91 (dd, J=12.2, 7.6 Hz, 1H), 2.67-2.46 (m, 3H), 2.17-2.04 (m, 1H), 1.91 (dddd, J=21.9, 15.4, 6.4, 4.7 Hz, 1H), 1.20 (d, J=5.0 Hz, 3H), 1.16 (d, J=5.5 Hz, 3H), 1.02 (d, J=13.6 Hz, 3H), 0.98 (d, J=13.6 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ ppm 211.3, 151.5 (d, J=34 Hz), 143.2, 134.6 (d, J=3 Hz), 133.1 (d, J=29 Hz), 130.5 (d, J=6 Hz), 130.0 (d, J=4 Hz), 128.7, 126.9, 126.3, 125.7, 55.7 (d, J=17 Hz), 41.5, 37.0 (d, J=18 Hz), 35.2, 35.0, 33.2, 32.9, 32.6, 32.3, 31.9, 31.6, 27.3, 26.3. 31P NMR (CDCl3, 202 MHz) δ ppm 15.1 (s). HRMS (TOF-ESI+) calcd for [M, C22H27OP]+ 338.1800. found 338.1805.

1. customTo a 40-mL scintillation vial equipped with a magnetic stir bar
2. customThe vial was sealed with
3. customa septa-top cap
4. custompurged with nitrogen gas for 10 minutes
5. dissolutionThe solid was then dissolved with anhydrous,
6. customdegassed dichloromethane (9 mL)
7. additionIn a separate 250-mL round bottom flask was added anhydrous
8. customdegassed dichloromethane (31 mL) which
9. customwas transferred by cannula to the reaction flask over the course of 3 minutes
10. stirringwas stirred at −78° C. for an hour
11. temperatureThe slurry was warmed to room temperature overnight
12. additionThe solution was charged into a separatory funnel
13. customthe phases were partitioned
14. customThe dichloromethane layer was collected
15. washthe aqueous layer was washed with dichloromethane (3×20 mL)
16. washThe combined organic layers were then washed with aqueous saturated sodium bicarbonate (50 mL)
17. dry with materialdried over sodium sulfate
18. filtrationfiltered
19. concentrationconcentrated in a rotary evaporator
20. customPurification of the crude product oil by silica gel column chromatography on an Isco CombiFlash system (120-g column