A keystone methodology in synthetic chemistry, metalation (metal-hydrogen exchange) reactions of aromatic compounds are usually the domain of highly reactive polar organometallics such as alkyllithium compounds, LICKOR (alkyllithium compounds cocomplexed with potassium tertbutoxide) superbases, or lithium amides. Strictly these reactions are lithiations (or potassiations) as the incoming lithium atom (or potassium atom) takes the place of the outgoing hydrogen atom. The lower-polarity metals magnesium, zinc, and aluminum generally form slow-reacting metalating agents which are ineffective towards aromatic compounds. Therefore, to attach these less reactive metals directly to an aromatic scaffold, the lithiated aromatic compound must be synthesized beforehand and then an additional metathetical reaction often involving a metal halide (for example, RMgX, ZnX2, or R2AlX) has to be carried out. The presence of the ionic halide often limits the range of solvents available for such reactions with hydrocarbons and arenes, which are generally ruled out in favor of polar substitutes (commonly ether or THF). Recently, however, it has been shown that pairing lithium (or another alkali metal) with one of these inferior multivalent metals in the same organometallic molecule (an '-ate' formulation), can generate 'synergic', mixed-metal reagents capable of directly magnesiating,[2,3] zincating, or aluminating aromatic substrates, thus circumventing the need for a subsequent metathesis. In addition to this new inorganic (metal) perspective, these synergic reagents can open up new organic horizons by promoting unusual regioselective deprotonations (for example, meta-orientated in the cases of toluene and N,Ndimethylaniline[ 6]) or special polydeprotonations (for example, 2,6-twofold in the case of naphthalene and 1,1',3,3'- fourfold in the cases of ferrocene and its Group 8 homologues[ 8]).
- alkali metals
Mulvey, R. E., Garcia-Alvarez, J., Kennedy, A. R., & Klett, J. (2007). Alkali-metal-mediated manganation: a method for directly attaching manganese(II) centers to aromatic frameworks. Angewandte Chemie, 46(7), 1105-1108. https://doi.org/10.1002/anie.200604542