Direct cross-coupling between an arylzinc reagent and an aryl halide was accomplished without any external catalyst, enabling efficient and selective formation of the corresponding biaryl compound with broad functional group compatibility.

Different homoleptic and heteroleptic lithium–zinc combinations were prepared, and structural elements obtained on the basis of NMR spectroscopic experiments and DFT calculations. In light of their ability to metalate anisole, pathways were proposed to justify the synergy observed for some mixtures. The best basic mixtures were obtained either by combining ZnCl₂⋅TMEDA (TMEDA=N,N,N′,N′-tetramethylethylenediamine) with [Li(tmp)] (tmp=2,2,6,6-tetramethylpiperidino; 3 equiv) or by replacing one of the tmp in the precedent mixture with an alkyl group. The reactivity of the aromatic lithium zincates supposedly formed was next studied, and proved to be substrate-, base-, and electrophile-dependent. The aromatic lithium zincates were finally involved in palladium-catalyzed cross-coupling reactions with aromatic chlorides and bromides.

1,4-Addition of bis(iodozincio)methane to simple α,β-unsaturated ketones does not proceed well; the reaction is slightly endothermic according to DFT calculations. In the presence of chlorotrimethylsilane, the reaction proceeded efficiently to afford a silyl enol ether of β-zinciomethyl ketone. The CZn bond of the silyl enol ether could be used in a cross-coupling reaction to form another CC bond in a one-pot reaction. In contrast, 1,4-addition of the dizinc reagent to enones carrying an acyloxy group proceeded very efficiently without any additive. In this case, the product was a 1,3-diketone, which was generated in a novel tandem reaction. A theoretical/computational study indicates that the whole reaction pathway is exothermic, and that two zinc atoms of bis(iodozincio)methane accelerate each step cooperatively as effective Lewis acids.

In situ mixtures of CdCl₂⋅TMEDA (0.5 equiv; TMEDA=N,N,N′,N′-tetramethylethylenediamine) or InCl₃ (0.33 equiv) with [Li(tmp)] (tmp=2,2,6,6-tetramethylpiperidino; 1.5 or 1.3 equiv, respectively) were compared with the previously described mixture of ZnCl₂⋅TMEDA (0.5 equiv) and [Li(tmp)] (1.5 equiv) for their ability to deprotonate anisole, benzothiazole, and pyrimidine. [(tmp)₃CdLi] proved to be the best base when used in tetrahydrofuran at room temperature, as 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 (CONEt₂, 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.

In the presence of organolithium bases phenyl dialkylcarbamates have previously been shown to undergo facile rearrangement to yield the corresponding salicylamides. However, heterometallic lithium diethyl(2,2,6,6-tetramethylpiperidido)zincate achieves the clean directed ortho-metallation (DoM) of phenyl dialkylcarbamates, with [C₆H₄{OC(O)NMe₂}{Zn(-TMP)Et}Li]₂ having been structurally characterized. DFT studies point to a stepwise deprotonative mechanism in which the zincate reagent exhibits kinetic amido basicity. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)