Reaction #166163

Reaction equation

(trimethylsilyl)diazomethane

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

Boron trifluoride diethyl etherate

phosphine

→

title compound

Yield 62.0%

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

Yield 62.0%

Solvents

hydrochloric acid

Conditions

Workup

1. 1
   OtherTo a 40-mL scintillation vial equipped with a magnetic stir bar
2. 2
   OtherThe vial was sealed with
3. 3
   Othera septa-top cap
4. 4
   Otherpurged with nitrogen gas for 10 minutes
5. 5
   workup.DISSOLUTIONThe solid was then dissolved with anhydrous,
6. 6
   Otherdegassed dichloromethane (9 mL)
7. 7
   workup.ADDITIONIn a separate 250-mL round bottom flask was added anhydrous
8. 8
   Otherdegassed dichloromethane (31 mL) which
9. 9
   Otherwas 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
    TemperatureThe slurry was warmed to room temperature overnight
12. 12
    workup.ADDITIONThe solution was charged into a separatory funnel
13. 13
    Otherthe phases were partitioned
14. 14
    OtherThe dichloromethane layer was collected
15. 15
    Washthe aqueous layer was washed with dichloromethane (3×20 mL)
16. 16
    WashThe combined organic layers were then washed with aqueous saturated sodium bicarbonate (50 mL)
17. 17
    Dryingdried over sodium sulfate
18. 18
    Filtrationfiltered
19. 19
    Concentrationconcentrated in a rotary evaporator
20. 20
    OtherPurification of the crude product oil by silica gel column chromatography on an Isco CombiFlash system (120-g column

Procedure

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.

Source