Stage #1: at 0 - 20℃; for 2.33333 h; Inert atmosphere
Stage #2: With hydrogenchloride In tetrahydrofuran; tert-butyl methyl ether; water at 0℃; for 0.416667 h;
|General procedure: Symmetric secondary phosphine oxides were prepared by the method of Hays by adding 1 eq. of diethylphosphite to 3.3 eq. of the corresponding Grignard reagent at 0 °C and warming to ambient temperature. A 100-mL round-bottom flask equipped with an addition funnel was evacuated/Ar filled, then charged with 33 mL of 1 M 4-methoxyphenylmagnesium bromide/THF (33 mmol, 3.3 eq.), and the solution cooled to 0 °C under Ar. A solution of 1.38 g of diethylphosphite (10 mmol, 1.0 eq.) in 10 mL of THF was then added dropwise over 10 min. The mixture was aged 10 min at 0 °C, then the bath was removed, and the mixture stirred 2 h at ambient temperature, then cooled again to 0 °C. 25 mL 0.1 N HCl (deoxygenated water) was then added dropwise over 20 min, then 25 mL methyl tert-butyl ether (MTBE) was added, and the mixture agitated well for 5 min. The upper organic phase was decanted from the separator and saved. To the lower phase was then added 20 mL of 1 N HCl (deoxygenated water) again, and it was extracted with CH2Cl2 (2 9 30 mL). The organic phase was combined with the first organic phase, then filtered through a celite pad, washing the pad with CH2Cl2, dried magnesium sulfate (MgSO4), and the solvents removed in vacuo. The crude material was chromatographed on silica gel eluting with 2percent MeOH/CH2Cl2, then recrystallized from hot ethyl acetate (EtOAc) to give 2.41 g of product (92percent) as a colorless solid. Colorless solid; YIELD = 92percent; 1H NMR (400 MHz, CDCl3) d: 8.01 (d, 1JHP = 473 Hz, 1H), 7.60 (dd, J = 13.8, 8.2 Hz, 4H), 6.97 (dd, J = 7.8, 2.4 Hz, 4H), 3.83 (s, 6H); 31P NMR (162 MHz, CDCl3) d: 21.0.