Preparation and ring-opening reactions of N-diphenylphosphinyl vinyl aziridines

Summary Predominantly (E)-N-diphenylphosphinyl vinyl aziridines are prepared by a reaction of N-diphenylphosphinyl imines with α-bromoallyllithium in the presence of freshly fused ZnCl2. These aziridines undergo a ring-opening reaction with a variety of carbon and heteronucleophiles, in good yield, and generally with good regioselectivity.

Analytical data corresponded exactly with those obtained using Method A.

With lower-order cuprate reagents
To dry CuI (5 equiv) in a flame-dried flask, under N 2 , was added diethyl ether (10 mL) and the suspension degassed. For the preparation of Me 2 CuLi the suspension was then cooled to 0 °C and MeLi (0.25 mL, 1.4 M in diethyl ether, 0.35 mmol, 1.7 equiv) added dropwise. The solution becomes yellow after addition of the first equivalent of MeLi and colourless after the addition of the second equivalent. For the preparation S7 of Et 2 CuLi, n-Bu 2 CuLi, sec-Bu 2 CuLi and tert-Bu 2 CuLi the suspension was cooled to −20 °C, and the alkyl lithium (3.5 equiv) was added dropwise affording a dark brown or black suspension. In all cases the solution was stirred for 20 min prior to further cooling to −78 °C. A degassed solution of the vinylaziridine (1 equiv), in ether (4 mL)/THF (1 mL), was added dropwise. The solution was stirred at −78 °C for 1 h and then at room temperature for 6 h, and then quenched by the addition of a saturated, aqueous solution of ammonium chloride (15 mL). The solution was partitioned between ammonium chloride and ethyl acetate, the aqueous layer extracted with ethyl acetate (3 × 15 mL), the organic layers combined and washed with brine (15 mL), dried (MgSO 4 ), filtered and the solvent removed in vacuo to give a yellow oil.
The oil was purified by flash column chromatography on silica gel with ethyl acetate/light petroleum (1:1) as an eluent.

With malonate
To diethyl malonate (typically 0.3-0.6 mmol, 1.1 equiv) in THF (1.5 mL), at room temperature, under argon, was added sodium hydride (1.1 equiv), and the colourless solution was left to stir for thirty minutes. Pd(PPh 3 ) 4 (3 mol %) was added to the reaction mixture and the dark orange suspension was further stirred for twenty five minutes. A solution of vinylaziridine (1 equiv) in THF (2.5 mL) was added dropwise, and the orange suspension was stirred at room temperature for four hours. The reaction mixture was quenched by the addition of a saturated aqueous solution of ammonium chloride (15 ml). The solution was partitioned between ammonium chloride and ethyl acetate, the aqueous layer extracted with ethyl acetate (3 × 15 mL), the organic layers combined and washed with brine (15 mL), dried (MgSO 4 ), S12 and filtered, and the solvent removed in vacuo to give a yellow oil. The oil was purified by flash column chromatography on silica gel (ethyl acetate/light petroleum (1:4); gradient elution to ethyl acetate).

With Grignard reagents
To magnesium (5 equiv) in diethyl ether (5 mL), under nitrogen, at 0 °C, was added MeI (5.4 equiv) in diethyl ether (1 mL), and the resulting mixture was stirred for thirty minutes, creating a grey suspension. A solution of the vinylaziridine (1 equiv) in THF (10 mL) was cooled to −78 °C and the ethereal suspension added dropwise.
Immediately, magnesium iodide precipitated as a colourless solid and the suspension was left to stir at −78 °C for one hour and then at room temperature for 6-8 hours.
The reaction mixture was quenched by the addition of a saturated aqueous solution of ammonium chloride (15 mL). The solution was partitioned between ammonium chloride and ethyl acetate, the aqueous layer extracted with ethyl acetate (3 × 15 mL), the organic layers combined and washed with brine (15 mL), dried (MgSO 4 ), and filtered, and the solvent removed in vacuo to give a yellow oil. The oil was purified by flash column chromatography on silica gel with ethyl acetate/light petroleum (1:1) as an eluent. S15

With stannyl cuprates
To freshly distilled diisopropylamine typically (0.4-0.8 mmol, 1 equiv) in THF (5 mL) at 0 °C, under nitrogen, was added n-butyllithium (2.5 M in hexanes, 1 equiv), S16 dropwise. The resulting pale yellow solution was then stirred at 0 °C for fifteen minutes and tri-n-butyltin hydride (1 equiv) was added dropwise and the reaction mixture left to stir for a further 15 minutes. The resulting n-Bu 3 SnLi solution was cooled to −20 °C and CuBr·Me 2 S (0.5 equiv) added in one portion. The brown reaction mixture was left to stir for thirty minutes and subsequently cooled to −78 °C.
A solution of the vinylaziridine (1 equiv) in THF (5 mL) was added dropwise. The solution was stirred at −78 °C for one hour and left to warm to room temperature overnight, after which time it was quenched by the addition of a saturated aqueous solution of ammonium chloride (15 mL). The solution was partitioned between ammonium chloride and light petroleum, the aqueous layer extracted with light petroleum (3 × 15 mL), the organic layers combined and washed with brine (15 mL), dried (MgSO 4 ), and filtered, and the solvent removed in vacuo to give a yellow solid.
This was purified by flash column chromatography on silica gel with ethyl acetate/light petroleum (1:1) as an eluent.