反应详情

温度

210 °C

A round bottom flask was charged with 2,2,6,6-tetramethyl-1-(2′,4′,6′-triisopropyl-3,6-dimethoxybiphenyl-2-yl)phosphinan-4-one (1.03 g, 2.02 mmol, 1.0 equiv) and purged with nitrogen for 15 minutes. Then nitrogen-sparged diethylene glycol (10.6 mL, 111 mmol, 55 equiv) was added and the flask was equipped with a Claisen adapter and a Dean-Stark trap. The flask was charged with hydrazine hydrate (0.892 mL, 10.1 mmol, 5 equiv, 55 wt % hydrazine) and potassium hydroxide (918 mg, 10.1 mmol, 5 equiv). The mixture was immersed in an oil bath at 170° C. The temperature of the bath was gradually increased to 210° C. over 1 hour and kept at that temperature for 7 hours. The reaction mixture was cooled to room temperature under a positive pressure of nitrogen. Reaction material that had condensed on the Claisen adapter was washed down into the reaction flask with ethyl acetate (5 mL). The phases were partitioned, and the organic layer was collected. The aqueous layer was washed with ethyl acetate (2×20 mL). The combined organic fractions were washed once with aqueous saturated sodium chloride, dried over sodium sulfate, filtered, and concentrated on a rotary evaporator. Purification of the crude material by silica gel column chromatography on an Isco CombiFlash system (40-g column; gradient: 2 column volumes heptane, ramp up to 85:15 heptane:ethyl acetate over 8 column volumes, hold at 85:15 for 4 column volumes) afforded the title compound as a white solid (266 mg, >99 area % by HPLC, 27% yield). 1H NMR (400 MHz, CDCl3) δ ppm 6.95 (s, 2H), 6.85 (d, J=8.8 Hz, 1H), 6.79 (d, J=8.8 Hz, 1H), 3.82 (s, 3H), 3.56 (s, 3H), 2.95 (hept, J=6.9 Hz, 1H), 2.49 (hept, J=6.7 Hz, 2H), 2.10-1.89 (m, 2H), 1.71-1.51 (m, 2H), 1.45-1.26 (m, 8H), 1.21 (d, J=6.8 Hz, 6H), 1.14 (s, 3H), 1.08 (s, 3H), 0.93 (d, J=6.7 Hz, 6H), 0.80 (d, J=8.6 Hz, 6H). 13C NMR (100 MHz, CDCl3) δ ppm 154.3, 151.9 (d, J=11 Hz), 146.3, 145.5 (d, J=2 Hz), 140.1 (d, J=42 Hz), 132.5 (d, J=9 Hz), 127.7 (d, J=46 Hz), 119.7, 110.6, 107.1, 54.3 (d, J=62 Hz), 40.8 (d, J=4 Hz), 34.0 (d, J=5 Hz), 33.4, 30.7, 30.3 (d, J=24 Hz), 30.1 (d, J=3 Hz), 25.5, 24.2 (d, J=13 Hz), 20.8. 31P NMR (CDCl3, 202 MHz) δ ppm −6.0 (br s). HRMS (TOF-ESI+) calcd for [M, C32H49O2P]+ 496.3470. Found 496.3465.

1. custompurged with nitrogen for 15 minutes
2. additionwas added
3. customthe flask was equipped with a Claisen adapter
4. customThe mixture was immersed in an oil bath at 170° C
5. temperatureThe reaction mixture was cooled to room temperature under a positive pressure of nitrogen
6. customReaction material that
7. customcondensed on the Claisen adapter
8. washwas washed down into the reaction flask with ethyl acetate (5 mL)
9. customThe phases were partitioned
10. customthe organic layer was collected
11. washThe aqueous layer was washed with ethyl acetate (2×20 mL)
12. washThe combined organic fractions were washed once with aqueous saturated sodium chloride
13. dry with materialdried over sodium sulfate
14. filtrationfiltered
15. concentrationconcentrated on a rotary evaporator
16. customPurification of the crude material by silica gel column chromatography on an Isco CombiFlash system (40-g column