BBr3裂解醚反应

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BBr₃是一种温和、优良的醚的去甲基化试剂，并且不影响分子中的酯基和双键，在许多天然产物的全合成中常使用它。一般使用CH₂Cl₂, benzene,  pentane作为溶剂，在-78 ℃到室温下进行。有一点需注意，当底物分子中杂原子数多时，应增加BBr₃量。使用BBr₃有一个最大的缺点是BBr₃对空气敏感，使用时会冒出大量气雾；并在加水后处理时常出现大量的络合物，此时最好使用其它的方法，否则后处理艰难并导致收率下降。BI₃, BCl₃的使用如同BBr_{3。反应后处理可以在低温下加入甲醇淬灭反应，生成的硼酸三甲酯可以减压蒸除。另外如果底物稳定性好的化，体系可以直接旋掉剩余的三溴化硼，然后再用甲醇淬灭，避免生成大量的酸气。}

   反应机理

反应实例

一、三溴化硼

Table 1.Cleavage of Ethers by Boron Tribromide

General Procedure forCleavage of Ether with BBr₃.  A weighed quantity of the ether (usually 15 to 20 g) is introduced into the reactionflask and cooled in an ice-bath. The calculated quantity of boron tribromide is slowly introduced through a dropping funnel. In all cases boron tribromide and ether are allowed to react in the ratio of 1 mol of boron tribromide to 3 mol of ether. After addition of boron tribromide, the reaction mixture is heated on a water bath for 40 min. The alkyl bromide is distilled directly from the reaction mixture. After removal of the alkyl bromide by distillation, the residure remaining in the flask is hydrolyzed with a minimum amount of 10% sodium hydroxide solution. The resulting solution is acidified with hydrochloric acid and extracted with ether.

【 F. L. Benton and T. E. Dillon, J. Am. Chem. Soc. 1942,64, 1128】

二、BX3和Me2S的络合物

其为BBr₃的改良方法。BBr₃或BCl₃和Me₂S的络合物是固体物，容易制备并在惰性气体中能长期保存。一般使用2到4倍量即可。

Table2.Cleavage of Ethers with BBr₃.S(CH3)₂ Complex

 a) Reaction run at 83°C. b) GLC yield. C) Isoated yield.

General Procedure for the Cleavage of Ethers with Boron Trihalide-Methyl sulfide Complex. To a flame-dried 100 mL flask under an atmosphere of nitrogen is added 1,2-dichloroethane (30 mL) and an amount of boron trihalide-methyl sulfide complex as indicated in Table 3. To this solution is added the desired number of equivalents of the aryl ether. The reaction mixture is stirred at reflux and monitored by either TLC or GLC whereconvenient. When the starting material disappears, the reaction mixture is hydrolyzed by adding water (30 mL), stirring for 20 min and diluting with ether. The organic phase is separated and washed with 1 M NaHCO₃ and the phenol is subsequentlytaken up with 1 N NaOH (3×20 mL). The combined NaOH washings are acidified and the product issubsequently extracted into ether, dried (MgSO₄) and the solvent isremoved in vacuum.

 【 H.Niwa, T. Hida and K. Yamada, Tetrahedron Lett.,1981, 22, 4239】

三、BBr₃/NaI/15-crown-5

这种体系为比BBr₃更强的去甲基化方法。也可用于脱除烷基甲基醚。

Table3.Dealkylation of Alkyl Methyl Ethers with BBr₃-NaI-15-crown-5

a) Yield of isoated alcohol.

Typical Procedure. Cleavage of3-Phenylpropanol Methyl Ether. To a stirred solution of 3-phenylpropanol methyl ether (103 mg, 0.687 mmol) in dry methylene chloride(0.5 mL) is added 0.3 M solution of 15-crown-5 (13.7 mL, 6 equiv.) with NaI in methylene chloride followed by addition of 1 M solution of BBr₃ (2.1 mL, 3 equiv.) in methylene chloride at -30°C under argon. The reaction mixtureis stirred at the same temperature for 3 hrs, quenched by the addition of saturated aqueous NaHCO₃ solution (2 mL) and worked up in the usualmanner. Chromatographic purification of the crude product gives the pure alcohol (93 mg, 100%), identical in all respects with an authentic sample.

 【 H.Niwa, T. Hida and K. Yamada, Tetrahedron Lett.,1981, 22, 4239】

四、Me₂BBr

文献报道，这个试剂去甲基化经由SN2机理，因此，非常有效的只是断裂C-O键，从而形成酚或醇，不易产生溴代副产物。

Table4.Cleavage of Ethers with (CH₃)₂BBr

Typical Procedure. Cleavageof 1-Methoxydecane. To a cold (0°C),stirred solution of 1-methoxydodecane (1.03 mmol) and triethylamine (0.21 mmol, to neutralize traces of free acid) in dry methylene chloride (4.1 mL) underargon, is added a solution of dimethylboron bromide (1.34 M, 0.99 mL) in methylene chloride. The coolingbath is then removed and the resultant solution is then stirred at roomtemperature for 3 hrs. The reaction mixture is then cooled to 0°C, quenched with saturated aqueoussodium bicarbonate (2 mL) and diluted with ether (30 mL). The organic layer isseparated, washed with saturated sodium bicarbonate (2 mL), water (2 mL) andbrine (2 mL). The aqueous washings are extracted with ether and the organiclayers are combined. After drying the resultant solution is concentrated andsubjected to flash chromatography to provide pure 1-dodecanol (89%).a) Yield of isoated Product.

【Y. Guindon, C. Yoakim and H. E. Morton, Tetrahedron Lett.,1983, 24, 2969】

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三溴化硼如何后处理？有个你没用过却很高效的方法。