烷基鋰化合物和帶有鄰位導(dǎo)向基團(tuán) (Directed Metalation Group--DMG)的芳烴反應(yīng)得到鄰位金屬中間體。好的鄰位導(dǎo)向基團(tuán)有很強的配位或螯合效應(yīng)，導(dǎo)致鄰位氫的酸性增強。
鄰位金屬中間體可以和各種親電試劑反應(yīng)，得到的產(chǎn)物的DMG可以復(fù)原，轉(zhuǎn)化為其他基團(tuán)，或直接除去。
一般情況下此類反應(yīng)都是低溫，強堿性條件，幾乎完全的鄰位選擇性是此反應(yīng)的特點。
反應(yīng)機理
電子密度大的取代基與鋰的相互作用，使得相鄰的位置被選擇性鋰化。
DMG沒必要必須是惰性基團(tuán):
強 DMGs: | -CON-R, -CONR2, | -N-COR, -N-CO2R |
| -OCONR2, -OMOM | |
-SO3R | ||
-CH=NR | -SO2NR2 | |
-CN | -SO2tBu | |
中等強度 | -CF3 | -NR2 |
-NC | ||
-OMe | ||
-F | ||
-Cl | ||
弱導(dǎo)向基團(tuán) | -CH2O- | -O- |
-C三C- | -S- | |
Ph |
反應(yīng)實例
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
C. E. Houlden, G. C. Lloyd-Jones, K. I. Brooker-Milburn, Org. Lett., 2010, 12, 3090-3092.
Selective Ortho and Benzylic Functionalization of Secondary and Tertiary p-Tolylsulfonamides. Ipso-Bromo Desilylation and Suzuki Cross Coupling Reactions
S. L. MacNeil, O. B. Familoni, V. Snieckus, J. Org. Chem, 2001, 66, 3662-3670.
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
S. Wunderlich, P. Knochel, Org. Lett., 2008, 10, 4705-4707.
One-Pot Synthesis of Phthalazines and Pyridazino-aromatics: A Novel Strategy for Substituted Naphthalenes
S. N. Kessler, H. A. Wegner, Org. Lett., 2012, 14, 3268-3271.
【 J. Am. Chem. Soc. 1988, 110, 7178】
【J. Org. Chem. 1984, 49, 1078】
【J. Am. Chem. Soc. 1992, 114, 10971】
