| Summary: | Building on recent advances in zincate chemistry, but going beyond the state-of-the-art, this project sought to advance the understanding of the mechanisms involved in alkali metalmediated zincation (AMMZn), as well as design a new type of mixed-metal reagent, magnesium-zinc hybrids, focussing on their applications in nucleophilic additions to ketones and direct zinc-iodine exchange reactions. Unveiling two new applications of the alkali metal TMP-zincates [(THF)Li(TMP)ZntBu₂] (1) and [(TMEDA)Na(TMP)ZntBu₂] (3), reaction with trimethyl(phenoxy)silane (12) allowed the isolation of the first intermediates of direct lateral zincation (DlZn) of an aromatic substrate, while the reaction of 3 with benzoylferrocene (17) has shown that two competing pathways are available: (i) remote 1,6-nucleophilic addition of a tert-butyl group to the phenyl ring of 17 and (ii) simultaneous α-deprotonation of the substituted cyclopentadienyl ring and 1,2-addition of a tert-butyl anion to the carbonyl group of the ketone. Shedding new light on the mechanism by which these alkali metal TMP-zincates react, the proposed intermediate species of the two-step mechanism (previously proposed by theoretical studies) [(THF)₂Li(o-C₆H₄OMe)ZnMe₂] (26) and [(THF)₃Li(o-C₆H₄OMe)ZntBu₂] (29) were prepared. Reactivity studies of 26 and 29 with TMP(H) provided the first tangible experimental evidence that the AMMZn of anisole by 1 proceeds via a two-step mechanism, which is greatly influenced by both the nature of the alkyl groups of the zincate (Me vs. tBu) and the polarity of the solvent in which the reaction is performed (hexane/benzene vs. THF). In addition, investigations into the seemingly simple stoichiometric salt metathesis reactions of Grignard reagents with ZnCl₂ led to the isolation of a series of magnesium-zinc hybrid species [(THF)Mg(μ-Cl)₂Zn(tBu)(Cl)] (34) and [(THF)Mg(μ-Cl)₃ZnR}₂] (R = tBu (36), nBu (37), Et (38), o-C₆H₄OMe (39)), formed via metathetical co-complexation. Altering the stoichiometry of these reactions (from 1:1 to 3:1) to mimic the conditions employed in ZnCl₂ catalysed reactions of Grignard reagents led to the formation of the alkyl-rich Mg-Zn hybrids [{Mg₂Cl₃(THF)₆}⁺{ZntBu₃}⁻] (40) and [{Mg₂Cl₃(THF)₆}+{Zn₂Et₅}⁻] (41). Probing the possible applications of these Mg-Zn hybrid species in various key synthetic methodologies revealed that 41 can be employed both stoichiometrically, and catalytically in the presence of an excess of EtMgCl, to perform the chemoselective alkylation of ketones. In contrast, the analogous 1st generation Mg-Zn hybrid 38 displayed diminished reactivity even towards activated ketones, although the addition of LiCl resulted in improved reactivity, hinting at the existence of trimetallic Li-Mg-Zn hybrid species in solution. Furthermore, 40 can readily undergo direct Zn-I exchange reactions with a wide range of functionalised aryl iodide substrates, demonstrating high atom economy, with the subsequent aryl-zincate species proving to be valuable precursors for Pd-catalysed Negishi cross-coupling reactions.
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