TMP-cadmiate: A Base for Efficient and Chemoselective Deprotonative Metallation Reactions of Aromatic Compounds

Efficient deprotonative cadmiation reactions of functionalized aromatics including heterocycles have been realized using TMP-cadmiate, (TMP)3CdLi (TMP = 2,2,6,6-tetramethylpiperidino). The reagent is compatible with reactive functional groups (amide, ester, nitrile and even ketone functions), heavy halogens (Br, I), five-membered aromatic heterocycles (furan, thiophene, oxazole, thiazole, and pyrrole derivatives) and even aromatic aza-heterocycles (pyridine, diazine compounds). Some heterocycles benefiting from doubly activated positions can be dimetallated at room temperature. The deprotonative cadmiation pathways/mechanisms have been studied using computational/theoretical techniques. Such generated lithium arylcadmiates have been evidenced using iodine. Alternative trappings of the species are palladium-catalyzed cross-coupling reactions or simple quench with acid chlorides.