Directed ortho Metalation in Hydrocarbon Solvents: Opposing Pi-Resonance Effects

Hydrocarbon solvents are known to be unreactive toward organolithium reagents and do not typically support ortho-metalation reactions without the aid of a promoter. An exception would be an arene substrate having the capability to bidentate complex to the reactive alkyllithium dimer, which enables ortho-metalation to occur in high yields. A second, more limiting exception, would be that the arene substrate possesses localized lone pairs of electrons, as is the case when the directed ortho metalating group (DMG) is located in the benzyl position. The work reported here centers upon developing a third and larger class of arene substrates that are exceptions to the general rule that metalation in hydrocarbon solvents requires the use of added promoter. When an arene is either 1,2- or 1,4- disubstituted with electron donating DMGs, the lone pairs of electrons on each of the DMG groups are more localized than is the case for a monosubstituted arene. The effect of localization allows the arene to complex more efficiently and therefore metalate. This localization effect we term the Opposing Pi Resonance Effect