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|
The Tetraethylphosphorodiamidate (OP(O)(NEt2)2) Directed Metalation Group (DMG). Directed ortho and Lateral Metalation and the Phospha Anionic Fries Rearrangement
M. Alessi, J. J. Patel, K. Zumbansen, V. Snieckus, Org. Lett., 2020, 22, 2147-2151.
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.
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.