Structural effects in lithiocuprate chemistry: the elucidation of reactive pentametallic complexes.

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.

Prehabilitation before general surgery: Worth the effort?

Prehabilitation, or interventions before surgery aimed at improving preoperative health and postoperative outcomes, has various forms. Although it may confer benefit to patients undergoing general surgery, this is not certain. Furthermore, although it may yield a net monetary gain, it is also likely to require substantial monetary and non-monetary investment. The impact of prehabilitation is highly variable and dependent on multiple factors. Physical function and pulmonary outcomes are likely to be improved by most forms of prehabilitation involving physical and multimodal exercise programmes. However, other surgical outcomes have demonstrated mixed results from prehabilitation. Within this issue, the measures used for evaluating baseline patient biopsychosocial health are important, and collecting sufficient data to accurately inform patient-centred prehabilitation programmes is only possible through thorough clinical and laboratory investigation and synthesised metrics such as cardiopulmonary exercise testing. Although a multimodal approach to prehabilitation is the current gold standard, societal factors may affect engagement with programmes that require a significant in-person activity. However, this is weighed against the substantial financial and non-financial investment that accompanies many programmes. The overall effectiveness and optimal mode of intervention across the discipline of general surgery remains unclear, and further research is needed to prove prehabilitation's full worth.

Lithiated tertiary carbanions display variable coordination modes: evidence from DFT and NMR studies.

Density functional calculations reveal that, whereas the reaction of 2-propyl-N,N-diisopropylbenzamide (6) with tBuLi in the presence of potentially tridentate donor ligands may result in lateral deprotonation of 6, the behavior of the Lewis base is non-trivial. The ability of N and O donor centers in the co-solvent to resist Li(+) coordination is found to be synonymous with interaction of lithium with the formally deprotonated carbanion center. Low-energy structures have been identified whose predicted (1)H and (13)C NMR spectroscopic shifts are in excellent agreement with experiment. Reaction of 2-isopropyl-N,N-diisopropylbenzamide (5) with tBuLi in the presence of bidentate Lewis base N,N,N',N'-tetramethylethylenediamine (TMEDA) yields material that is suggested by NMR spectroscopy to be laterally deprotonated and to have the formulation 5-Li(l)·TMEDA. In spite of the tertiary aliphatic group at the 2-position in 5, X-ray crystallography reveals that the crystalline material isolated from the treatment of 5/(-)-sparteine with tBuLi is a lateral lithiate in which amide coordination and solvation by bidentate Lewis base results in the Li(+) ion interacting with the deprotonated α-C of the 2-iPr group (2.483(8) Å). The tertiary carbanion center remains essentially flat and the adjacent aromatic system is highly distorted. The use of a chiral co-solvent results in two diastereomeric conformers, and their direct observation in solution suggests that interconversion is slow on the NMR timescale.

Deprotonative metalation of chloro- and bromopyridines using amido-based bimetallic species and regioselectivity-computed CH acidity relationships.

A series of chloro- and bromopyridines have been deprotometalated by using a range of 2,2,6,6-tetramethylpiperidino-based mixed lithium-metal combinations. Whereas lithium-zinc and lithium-cadmium bases afforded different mono- and diiodides after subsequent interception with iodine, complete regioselectivities were observed with the corresponding lithium-copper combination, as demonstrated by subsequent trapping with benzoyl chlorides. The obtained selectivities have been discussed in light of the CH acidities of the substrates, determined both in the gas phase and as a solution in THF by using the DFT B3LYP method.

New avenues in the directed deprotometallation of aromatics: recent advances in directed cupration.

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.

The redox effect of the [1,2-(NH)2C6H4]2- ligand in the formation of transition metal compounds.

Reactions of the [1,2-(NH)(2)C(6)H(4)](2-) dianion (LH(2)(2-)) with Cp(2)M(II) (M = V, Mn) lead to complete or partial oxidation of the metals (M), giving the V(III) compound [(η(5)-Cp)(LH(2))(2)VV(LH(2))](-)[Li(THF)(4)](+) (1) and Mn(II)(4)Mn(III)(2) oxo cage [Mn(6)(LH(2))(6)(µ(6)-O)(THF)(4)] (2).

Expanding the tools available for direct ortho cupration--targeting lithium phosphidocuprates.

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.