邻位金属化反应（Directed ortho Metalation）

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

Efficient Two-Step Synthesis of Salicylaldehydes via Directed ortho-Lithiation of in situ N-Silylated O-Aryl N-Isopropylcarbamates

M. Kauch, D. Hoppe, Synthesis, 2006, 1575-1577.

Directed Ortho-Metalation of Unprotected Benzoic Acids. Methodology and Regioselective Synthesis of Useful Contiguously 3- and 6-Substituted 2-Methoxybenzoic Acid Building Blocks

T.-H. Nguyen, A.-S. Castanet, J. Mortier, Org. Lett., 2006, 8, 765-768.

Facile Double-Lithiation of a Transient Urea: Vicarious ortho-Metalation of Aniline Derivatives

Selective Ortho and Benzylic Functionalization of Secondary and Tertiary p-Tolylsulfonamides. Ipso-Bromo Desilylation and Suzuki Cross Coupling Reactions

Palladium-Catalyzed Aryl-Aryl Cross-Coupling Reaction Using ortho-Substituted Arylindium Reagents

M. A. Pena, J. P. Sestelo, L. A. Sarandeses, J. Org. Chem., 2007, 72, 1271-1275.

High Temperature Metalation of Functionalized Aromatics and Heteroaromatics using (tmp)2Zn·2MgCl2·2LiCl and Microwave Irradiation

One-Pot Synthesis of Phthalazines and Pyridazino-aromatics: A Novel Strategy for Substituted Naphthalenes

【 J. Am. Chem. Soc. 1988, 110, 7178】

【J. Org. Chem. 1984, 49, 1078】

【J. Am. Chem. Soc. 1992, 114, 10971】

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】

参考文献

一、Organic Chemistry Portal：http://www.organic-chemistry.org/namedreactions/directed-ortho-metalation.shtm

二、化学空间：https://cn.chem-station.com/reactions/%e5%8f%96%e4%bb%a3%e5%8f%8d%e5%ba%94/2014/06/%e9%82%bb%e4%bd%8d%e9%87%91%e5%b1%9e%e5%8c%96-directed-ortho-metalation.html

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