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Directed ortho Metalation (DOM)

The reaction of an alkyllithium compound with an arene bearing a "Directed Metalation Group" (DMG) normally leads to an ortho-metalated intermediate. Good DMG's are strong complexing or chelating groups that have the effect of increasing the kinetic acidity of protons in the ortho-position.

The ortho-metalated intermediate can be reacted with a variety of electrophiles, after which the DMG can be retained if desired, converted to a different functional group, or in some cases removed.


Mechanism of Directed Ortho Metalation

The DMG does not necessarily have to be inert:

strong DMGs: -CON-R, -CONR2 -N-COR, -N-CO2R
-OCONR2, -OMOM
-SO3R
-CH=NR -SO2NR2
-CN -SO2tBu
moderate -CF3 -NR2
-NC
-OMe
-F
-Cl
weak -CH2O- -O-
-CC- -S-
Ph

Recent Literature


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)2Zn2MgCl22LiCl 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.