Deprotonative Metalation of Functionalized Aromatics Using Mixed Lithium-Cadmium, Lithium-Indium, and Lithium-Zinc Species

In situ mixtures of CdCl2 center dot TMEDA (0.5 equiv; TMEDA - N,N,N',N'-tetrarrethylethylenediamine) or InCl; (0.33 equiv) with (Li(tmp), (trop=2,2,6,6-tetramethylpiperidino; 1.5 or 1 3 equiv. respectively) were compared with the previously described mixture of ZnCl2 center dot TMEDA. (0.5 equiv) and [Li(tmp)] (1.5 equiv) for their ability to deprotonate anisole. benzothiazole, and pyrimidine. [(tmp)(3)CdL1] proved to he the base, base when used to tetrahydrofuran at room temperature. its demonstrated by subsequent trapping with iodine. The Cd-Li base then proved suitable for the metalation of a large range of aromatics including benzenes bearing reactive functional groups (CONFt(2), CO2Me, CN, COPh) or heavy halogens (Br, I), and heterocycles (from the furan, thiophene, pyrrole. oxazole, thiazole, pyridine. and diazine series). Five membered heterocycles benefiting from doubly activated positions were similarly dideprotonated at room temperature. The aromatic lithium cadmates thus obtained were involved in palladium-catalyzed cross-coupling reactions or simply quenched with acid chlorides.