تفاعل #166163

معادلة التفاعل

(trimethylsilyl)diazomethane

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

Boron trifluoride diethyl etherate

phosphine

→

title compound

المردود 62.0%

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

المردود 62.0%

المذيبات

hydrochloric acid

ظروف التفاعل

المعالجة

1. 1
   أخرىTo a 40-mL scintillation vial equipped with a magnetic stir bar
2. 2
   أخرىThe vial was sealed with
3. 3
   أخرىa septa-top cap
4. 4
   أخرىpurged with nitrogen gas for 10 minutes
5. 5
   workup.DISSOLUTIONThe solid was then dissolved with anhydrous,
6. 6
   أخرىdegassed dichloromethane (9 mL)
7. 7
   workup.ADDITIONIn a separate 250-mL round bottom flask was added anhydrous
8. 8
   أخرىdegassed dichloromethane (31 mL) which
9. 9
   أخرىwas 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
    درجة الحرارةThe slurry was warmed to room temperature overnight
12. 12
    workup.ADDITIONThe solution was charged into a separatory funnel
13. 13
    أخرىthe phases were partitioned
14. 14
    أخرىThe dichloromethane layer was collected
15. 15
    غسيلthe aqueous layer was washed with dichloromethane (3×20 mL)
16. 16
    غسيلThe combined organic layers were then washed with aqueous saturated sodium bicarbonate (50 mL)
17. 17
    تجفيفdried over sodium sulfate
18. 18
    ترشيحfiltered
19. 19
    تركيزconcentrated in a rotary evaporator
20. 20
    أخرىPurification of the crude product oil by silica gel column chromatography on an Isco CombiFlash system (120-g column

الإجراء التجريبي

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.

المصدر