反応 #166163

反応方程式

(trimethylsilyl)diazomethane

1-(biphenyl-2-yl)-2,2,6,6-tetramethylphosphinan-4-one

Boron trifluoride diethyl etherate

phosphine

→

title compound

収率 62.0%

1-(Biphenyl-2-yl)-2,2,7,7-tetramethylphosphepan-4-one

収率 62.0%

溶媒

hydrochloric acid

反応条件

後処理

1. 1
   その他To a 40-mL scintillation vial equipped with a magnetic stir bar
2. 2
   その他The vial was sealed with
3. 3
   その他a septa-top cap
4. 4
   その他purged with nitrogen gas for 10 minutes
5. 5
   workup.DISSOLUTIONThe solid was then dissolved with anhydrous,
6. 6
   その他degassed dichloromethane (9 mL)
7. 7
   workup.ADDITIONIn a separate 250-mL round bottom flask was added anhydrous
8. 8
   その他degassed dichloromethane (31 mL) which
9. 9
   その他was transferred by cannula to the reaction flask over the course of 3 minutes
10. 10
    workup.STIRRINGwas stirred at −78° C. for an hour
11. 11
    温度The slurry was warmed to room temperature overnight
12. 12
    workup.ADDITIONThe solution was charged into a separatory funnel
13. 13
    その他the phases were partitioned
14. 14
    その他The dichloromethane layer was collected
15. 15
    洗浄the aqueous layer was washed with dichloromethane (3×20 mL)
16. 16
    洗浄The combined organic layers were then washed with aqueous saturated sodium bicarbonate (50 mL)
17. 17
    乾燥dried over sodium sulfate
18. 18
    ろ過filtered
19. 19
    濃縮concentrated in a rotary evaporator
20. 20
    その他Purification of the crude product oil by silica gel column chromatography on an Isco CombiFlash system (120-g column

実験手順

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 Min 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.

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