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邻位金属化反应(Directed ortho Metalation)

(2022-07-06 17:21:14) 下一个

烷基锂化合物和带有邻位导向基团 (Directed Metalation Group--DMG)的芳烃反应得到邻位金属中间体。好的邻位导向基团有很强的配位或螯合效应,导致邻位氢的酸性增强。

邻位金属中间体可以和各种亲电试剂反应,得到的产物的DMG可以复原,转化为其他基团,或直接除去。

一般情况下此类反应都是低温,强碱性条件,几乎完全的邻位选择性是此反应的特点。

反应机理

电子密度大的取代基与锂的相互作用,使得相邻的位置被选择性锂化。

DMG没必要必须是惰性基团:

反应实例

To a stirred solution of 3-phenylsydnone (1) (0.25 g, 1.54 mmol) in dry THF (100 ml) at

-78℃ under an atmosphere of dry nitrogen gas was added N, N, N’,

N’-tetramethylethylenediamine (0.29 ml, 1.93 mmol) then n-butyllithium (2.31 ml, 3.47

mmol, 15 M in pentane) dropwise. After 0.5 h, the appropriate

2-chloro-N-methoxy-N-methylacetamide (1.93 mmol) was added to the golden yellow

solution and, after a additional 1h, the mixture was quenched with aqueous hydrochloric acid

(100ml, 10% v/v) then extracted with dichloromethane (3*100 ml). the combined organic

layers were dried (MgSO4) and the solvent removed in vacuo to afford the corresponding

o-acylated sydnone 4as an oil which was puriied by colum chromatography to afford colorless

crystals. Yield 86%.

Tetrahedron Lett.; EN; 39; 12; 1998; 1509-1512】

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