前一段时间发布过利用DPPA通过Mitsunobu反应取代羟基合成叠氮化物的文章（点击： Mitsunobu反应合成叠氮化合物 ），但 Mitsunobu反应会生成大量的副产物，不易纯化。下面介绍一种可以得到相同产物的方法，利用DPPA和DBU，可以取代羟基得到构型翻转的叠氮化物，此反应生成副产物磷酸二苯酯和DBU盐都可以用水洗掉，可以很好的避免消除产物。但此反应，只对于活性醇（苄醇或羧酸α位羟基）效果较好。

反应机理

在DBU碱性条件下醇和DPPA反应得到磷酸酯，取代下来的DBU叠氮盐对磷酸酯进行SN2反应，构型翻转。

General Procedure:A mixture of the alcohol (10 mmol) and diphenylphosphoryl azide (3.3 g, 12 mmol) were dissolved in dry solvent (18 ml). To the mixture at 0°C, under N2 was added neat l,8-diazabicyclo[5.4.0]undec-7-ene (1.8 ml, 12 mmol). The reaction was warmed to room temperature and stirred until complete. The resulting two phase mixture was washed with H2O (2 x 10 ml) and 5% HC1 (10 ml). The organic phase was concentrated in vacuo and purified by silica gel chromatography using 95:5

展开全文

(v:v) hexane: ethyl acetate.

(S)-(+)-ethyl lactate(2.54 g, 21.5 mmol) and DPPA (7 g, 25.4 mmol) were reacted with DBU (3.1 ml, 20.7 mmol) in THF (35 ml) at 20°C for 48 h. The batch was diluted with 5:1 hexane:ethyl acetate (120 ml) and washed with H2 O (2 x 40 ml) and 5% HC1 (40 ml). The yield by HPLC assay was 87%. HPLC conditions [CH3CN:H2 0 gradient elution from 50:50 to 70:30 in 15 min,

flow =1.5 ml/min, U.V.detection at 210 nm] tR 4„5 min. The batch was concentrated and distilled to afford 2.2 gm (72%) of the volatile azide.

参考文献

J. Org. Chem., 1993, 58(22), pp 5886–5888

其他应用

DPPA为缩合剂合成酰胺示例

To solution of this free amine 30(0.270 g, 0.96 mmol) was added DMF (5 mL),(2-phthalimidoethoxy)acetic acid 29(0.237 g, 0.96 mmol), DPPA (0.25 mL, 1.15mmol) and Et 3 N (0.29 mL, 2.11 mmol) at 0 ℃while stirring. The ice bath was removed after two hours and the reaction was stirred at R.T. overnight. EtOAc (70 mL) was added and the solution wasextracted successively with 10% citric acid, H2O, saturated NaHCO 3 solution, H 2 O, and saturated NaCl solution (20 mL each), dried(anhydrous MgSO 4 ) and finnaly evaporated in vacuo. The oily residue was purified by columnchromatography on silica gel, eluting with 7:1 CHCl 3 -MeOH to givethe desired product 31as a white solid. Yield: 81% (two steps)。