The pivalates RZnOPiv⋅Mg(OPiv)X⋅n LiCl (OPiv=pivalate; R=aryl; X=Cl, Br, I) stand out amongst salt-supported organometallic reagents, because apart from their effectiveness in Negishi cross-coupling reactions, they show more resistance to attack by moist air than conventional organometallic compounds. Herein a combination of synthesis, coupling applications, X-ray crystallographic studies, NMR (including DOSY) studies, and ESI mass spectrometric studies provide details of these pivalate reagents in their own right. A p-tolyl case system shows that in [D8]THF solution these reagents exist as separated Me(p-C6H4)ZnCl and Mg(OPiv)2 species. Air exposure tests and X-ray crystallographic studies indicate that Mg(OPiv)2 enhances the air stability of aryl zinc species by sequestering H2O contaminants. Coupling reactions of Me(p-C6H4)ZnX (where X=different salts) with 4-bromoanisole highlight the importance of the presence of Mg(OPiv)2. Insight into the role of LiCl in these multicomponent mixtures is provided by the molecular structure of [(THF)2Li2(Cl)2(OPiv)2Zn].

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Quinine, nicotine, and related electron-rich amino-substituted pyridines were readily metalated using LiCl-solubilized TMP (2,2,6,6-tetramethylpiperidyl) bases in the presence of BF(3)·OEt(2). A full pyridine functionalization of all five positions of the pyridine ring can be realized by using an appropriate combination of TMP bases in the presence or absence of BF(3)·OEt(2).

The reactivity of a representative set of 17 organozinc pivalates with 18 polyfunctional druglike electrophiles (informers) in Negishi cross-coupling reactions was evaluated by high-throughput experimentation protocols. The high-fidelity scaleup of successful reactions in parallel enabled the isolation of sufficient material for biological testing, thus demonstrating the high value of these new solid zinc reagents in a drug-discovery setting and potentially for many other applications in chemistry. Principal component analysis (PCA) clearly defined the independent roles of the zincates and the informers toward druggable-space coverage.

A wide range of air-stable, solid, polyfunctional aryl and heteroarylzinc pivalates were efficiently prepared by either magnesium insertion or Hal/Mg exchange followed by transmetalation with Zn(OPiv)2 (OPiv = pivalate). By reducing the amount of LiCl the air stability could be significantly enhanced compared with previously prepared reagents. An alternative route is directed magnesiation using TMPMgCl⋅LiCl (TMP = 2,2,6,6-tetramethylpiperidyl) followed by transmetalation with Zn(OPiv)2 or, for very sensitive substrates, direct zincation by using TMPZnOPiv. These zinc reagents not only show excellent stability towards air, but they also undergo a broad range of C-C bond-formation reactions, such as allylation and carbocupration reactions, as well as addition to aldehydes and 1,4-addition reactions. Acylation reactions can be performed by using an excess of TMSCl to overcome side reactions of the omnipresent pivalate anion.

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A wide range of aryl and heteroaryl zinc pivalates bearing sensitive functionalities were prepared by selective metalation using TMPZnOPiv•LiCl, a new hindered zinc amide base. The new zinc reagents are easy-to-handle solids, which maintain their activity almost entirely (>95%) after 4 h of air exposure and smoothly undergo Negishi cross-couplings and reactions with various electrophiles such as Cu(I)-catalyzed acylations and allylations.

Treatment of pyridines, quinoline and methylthiopyrazine with the frustrated Lewis pair TMPMgClÁBF 3 (1) leads to organotrifluoro borates which react readily with a variety of aromatic aldehydes in the absence of a transition metal catalyst.