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Recent advances in the selective deprotometallation of aromatic reagents using alkali metal cuprates are reported. The ability of these synergic bases to effect deprotonation under the influence of a directing group is explored in the context of achieving new and more efficient organic transformations whilst encouraging greater ancillary group tolerance by the base. Developments in our understanding of the structural chemistry of alkali metal cuprates are reported, with both Gilman cuprates of the type R2CuLi and Lipshutz and related cuprates of the type R2Cu(X)Li2 (X = inorganic anion) elucidated and rationalised in terms of ligand sterics. The generation of new types of cuprate motif are introduced through the development of adducts between different classes of cuprate. The use of DFT methods to interrogate the mechanistic pathways towards deprotonative metallation is described. Theoretical modelling of in situ rearrangements undergone by the cuprate base are discussed, with a view to understanding the relationship between R2CuLi and R2Cu(X)Li2, their interconversion and the implications of this for cuprate reactivity. The advent of a new class of adduct between different cuprate types is developed and interpreted in terms of the options for expelling LiX from R2Cu(X)Li2. Applications in the field of medicinal chemistry and (hetero)arene derivatization are explored.

TMPLi (TMP=2,2,6,6-tetramethylpiperidide) reacts with Cu(I) salts in the presence of Et2O to give the dimers [{(TMP)2Cu(X)Li2 (OEt2)}2] (X=CN, halide). In contrast, the use of DMPLi (DMP=cis-2,6-dimethylpiperidide) gives an unprecedented structural motif; [{(DMP)2CuLi(OEt2)}2LiX] (X=halide). This formulation suggests a hitherto unexplored route to the in situ formation of Gilman-type bases that are of proven reactivity in directed ortho cupration., (© 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.)

An array of copper and copper-zinc based nanoparticles (NPs) have been fabricated employing a variety of polymeric capping agents. Analysis by TEM, XRPD and XPS suggests that by manipulating reagent, reductant and solvent conditions it is possible to achieve materials that are mono-/narrow disperse with mean particle sizes in the ≤10 nm regime. Oxidative stability in air is achieved for monometallic NPs using poly(methyl methacrylate) (PMMA) anti-agglomerant in conjunction with a variety of reducing conditions. In contrast, those encapsulated by either poly(1-vinylpyrrolidin-2-one) (PVP) or poly(4-vinylpyridine) (PVPy) rapidly show Cu(2)O formation, with all data suggesting progressive oxidation from Cu to Cu@Cu(2)O core-shell structure and finally Cu(2)O. Bimetallic copper-zinc systems, reveal metal segregation and the formation of Cu(2)O and ZnO. Catalysts have been screened in the synthesis of 1,2,3-triazoles through multicomponent azide-alkyne 1,3-dipolar cycloaddition. Whereas PMMA- and PVPy-coating results in reduced catalytic activity, those protected by PVP are highly active, with quantitative triazole syntheses achieved at room temperature and with catalyst loadings of 0.03 mol% metal for Cu and CuZn systems prepared using NaH(2)PO(2), N(2)H(4) or NaBH(4) reductants.

Reaction of in situ generated lithium phosphides with 0.5 eq. Cu(I) is employed as a means of targeting lithium phosphidocuprates of either Gilman- or Lipshutz-type formulation--e.g., (R(2)P)(2)CuLi·n(LiX) (n = 0, 1). For R = Ph, X = CN in toluene followed by thf or R = Ph, X = I in thf/toluene an unexpected product results. [(Ph(2)P)(6)Cu(4)][Li·4thf](2)1 reveals an ion-separated structure in the solid state, with solvated lithium cations countering the charge on an adamantyl dianion [(Ph(2)P)(6)Cu(4)](2-). Deployment of R = Ph, X = CN in thf affords a novel network based on the dimer of Ph(2)PCu(CN)Li·2thf 2 with trianions based on 6-membered (PCu)(3) rings acting as nodes in the supramolecular array and solvated alkali metal counter-ions completing the linkers. Cy(2)PLi (Cy = cyclohexyl) has been reacted with CuCN in thf/toluene to yield Gilman-type lithium bis(phosphido)cuprate (Cy(2)P)(2)CuLi·2thf 3 by the exclusion of in situ generated LiCN. A polymer is noted in the solid state.

A modified polyol-based reduction method in ethylene glycol that incorporates poly(N-vinylpyrrolidone) (PVP, M(av) = 10,000; 40,000; 55,000) as polymeric anti-agglomerant alongside a reducing additive (N(2)H(4) x H(2)O, NaBH(4), NaH(2)PO(2) x H(2)O) has been employed to investigate the influence of synthetic parameters on the purity, morphology and stability of an array of polymer-coated copper nanoparticles. While data point to ethylene glycol being capable of acting as a reductant in this system, the use of NaH(2)PO(2) x H(2)O as co-reductant in tandem with the presence of PVP (M(av) 40,000) has rendered nanoparticles with a mean size distribution of 9.6 +/- 1.0 nm that exhibit stability towards oxidation for several months. These data allow us to probe fundamentally how oxidatively stable nano-copper might be achieved.

EU legislation requires a multimedia exposure assessment for substances supplied within the EU. Dietary intake is the main source of exposure for the majority of the population hence an essential component of the human risk assessment. This paper describes the available data for dietary copper and its use in estimating daily intake including variability and determinants of exposure. Typical and reasonable worst-case estimates are derived for the general population from the available peer reviewed literature. Intakes from drinking water are found to exhibit more variability than those from food. Therefore, different exposure scenarios are derived to reflect the range of acute and chronic exposures that may occur. Estimates of typical copper intakes for the EU population are in the range 0.8-1.8 mg/day. Typical copper intakes of men are higher than those of women while the intake among the general adult population is higher than that of the elderly. Intakes of both men and women are generally close to the WHO normative requirements but may be somewhat lower in specific locations where background levels of copper are unusually low. Alcoholic beverages represent minor contribution daily copper intakes. Intakes for children are rather variable ranging broadly from 0.7 to 1.5 mg/day and are somewhat age and sex dependent. Greater uncertainty applies to the assessment of local exposure incorporating food produced on land directly impacted by contemporary copper industry emissions. Specifically, the extent to which soil is enriched in copper in these conditions is unclear. However, effective homeostatic control mechanisms in plants limit uptake and transfer to the human food chain. A best estimate of 0.25 mg/day in addition to regional exposure was derived. Drinking water is estimated to contribute only marginally to total copper intake in most cases. Higher intakes may occur in areas of poor water quality and/or corroded distribution systems. Such elevated exposures appear unusual but their frequency is unknown.

TMPLi (TMP=2,2,6,6-tetramethylpiperidide) reacts with CuI salts in the presence of Et2O to give the dimers [{(TMP)2Cu(X)Li2(OEt2)}2] (X=CN, halide). In contrast, the use of DMPLi (DMP= cis-2,6-dimethylpiperidide) gives an unprecedented structural motif; [{(DMP)2CuLi(OEt2)}2LiX] (X=halide). This formulation suggests a hitherto unexplored route to the in situ formation of Gilman-type bases that are of proven reactivity in directed ortho cupration. [ABSTRACT FROM AUTHOR]

A modified polyol-based reduction method in ethylene glycol that incorporates poly(N-vinylpyrrolidone) (PVP, Mav= 10 000; 40 000; 55 000) as polymeric anti-agglomerant alongside a reducing additive (N2H4·H2O, NaBH4, NaH2PO2·H2O) has been employed to investigate the influence of synthetic parameters on the purity, morphology and stability of an array of polymer-coated copper nanoparticles. While data point to ethylene glycol being capable of acting as a reductant in this system, the use of NaH2PO2·H2O as co-reductant in tandem with the presence of PVP (Mav40 000) has rendered nanoparticles with a mean size distribution of 9.6 ± 1.0 nm that exhibit stability towards oxidation for several months. These data allow us to probe fundamentally how oxidatively stable nano-copper might be achieved. [ABSTRACT FROM AUTHOR]

Abstract: The efficiency of the deprotocupration–aroylation of 2-chloropyridine using lithiocuprates prepared from CuX (X=Cl, Br) and LiTMP (TMP=2,2,6,6-tetramethylpiperidido, 2 equiv) was investigated. CuCl was identified as a more suitable copper source than CuBr for this purpose. Different diaryl ketones bearing a halogen at the 2 position of one of the aryl groups were synthesized in this way from azines and thiophenes. These were then involved in palladium-catalyzed ring closure: substrates underwent expected CH-activation-type arylation to afford fluorenone-type compounds, and were also subjected to cyclization reactions leading to xanthones, notably in the presence of oxygen-containing substituents or reagents. [Copyright &y& Elsevier]

Abstract: Crystals of a lithiocuprate prepared from copper(I) chloride and lithium 2,2,6,6-tetramethylpiperidide (2equiv) were isolated and analyzed by X-ray diffraction as (TMP)2Cu(Cl)Li2·THF. The observation of this species is consistent with its having a role in deprotocupration–aroylation. Phenyl pyridyl ketones, phenyl quinolyl ketones, and phenyl thienyl ketones were prepared in tetrahydrofuran using the lithiocuprate and aroyl chorides as electrophiles. Diaryl ketones bearing a chloro group at the 2 position (of a pyridyl or phenyl group) thus synthesized were next converted through palladium-catalyzed ring closure to polycycles of the 5H-indeno[1,2-b]pyridin-5-one, 11H-indeno[1,2-b]quinolin-11-one, 9H-indeno[2,1-c]pyridin-9-one, and 8H-indeno[2,1-b]thiophen-8-one families. [Copyright &y& Elsevier]