Pablo García-Álvarez

Unmasking Representative Structures of TMP-Active Hauser and Turbo-Hauser Bases†

The molecular engines that drive enhanced magnesiations are unveiled through structural elucidation of a 2,2,6,6-tetramethylpiperidide (TMP) Hauser base and its turbo model (see structure; Mg green, Li violet, C purple, O red, N blue, Cl yellow).

Exposing the hidden complexity of stoichiometric and catalytic metathesis reactions by elucidation of Mg-Zn hybrids

Studying seemingly simple metathesis reactions between ZnCl2 and tBuMgCl has, surprisingly, revealed a much more complex chemistry involving mixed magnesium-zinc compounds that could be regarded as Mg-Zn hybrids. Thus, the reaction of equimolar amounts of ZnCl2 and tBuMgCl reveals the formation of the unprecedented mixed Mg-Zn complex [(THF)4Mg(μ-Cl)2Zn(tBu)(Cl)] (1), as a result of the co-complexation of the two anticipated exchange products of the metathesis. This magnesium zincate adopts a contacted ion-pair structure, closely related to Knochel’s pioneering “Turbo” Grignard reagents. Furthermore, a second coproduct identified in this reaction is the solvent-separated mixed magnesium-zinc chloride complex [{Mg(THF)6}2+{Zn2Cl6}2-] (3) that critically diminishes the amount of ZnCl2 available for the intended metathesis reaction to take place. In another surprising result, when the reaction is carried out by using an excess of 3 M equivalents of the Grignard reagent (closer to the catalytic conditions employed by synthetic chemists), solvent-separated magnesium trialkyl zincate [{Mg2Cl3(THF)6}+{Zn(tBu)3}-] (4) is obtained that can be viewed as a model for the active species involved in the increasingly important organic transformations of Grignard reagents catalysed by ZnCl2. Furthermore, preliminary reactivity studies reveal that complex 4 can be used as an effective new reagent for direct Zn-I exchange reactions that allow the preparation and structural identification of the magnesium tris(aryl) zincate [{Mg2Cl3(THF)6}+{Zn(p-Tol)3}-] (5) that represents the first example of complete 3-fold activation of a zincate in a Zn-I exchange reaction which, in turn, can efficiently be used as a precursor for Negishi cross-coupling reactions.

The N-heterocyclic carbene chemistry of transition-metal carbonyl clusters.

In the last decade, chemists have dedicated many efforts to investigate the coordination chemistry of N-heterocyclic carbenes (NHCs). Although most of that research activity has been devoted to mononuclear complexes, transition-metal carbonyl clusters have not escaped from these investigations. This critical review, which is focussed on the reactivity of NHCs (or their precursors) with transition-metal carbonyl clusters (mostly are of ruthenium and osmium) and on the transformations underwent by the NHC-containing species initially formed in those reactions, shows that the polynuclear character of these metallic compounds or, more precisely, the close proximity of one or more metal atoms to that which is or can be attached to the NHC ligand, is responsible for reactivity patterns that have no parallel in the NHC chemistry of mononuclear complexes (74 references).

“LiZn(TMP)3”, a Zincate or a Turbo‐Lithium Amide Reagent? DOSY NMR Spectroscopic Evidence

DOSY NMR studies (see picture; TMP=2,2,6,6-tetramethylpiperidide; TMEDA=N,N,N′,N′-tetramethylethylenediamine) reveal the true nature of the synthetically useful basic mixture formed by reacting three equivalents of LiTMP with one of (TMEDA)⋅ZnCl2 in THF. Surprisingly, Zn(TMP)2 is just a spectator of the mutual interactions shown between LiTMP and the LiCl coproduct released from the transmetalation/“salt elimination” reaction.

Structurally engineered deprotonation/alumination of THF and THTP with retention of their cycloanionic structures

Metalation has served well for over 80 years as a vehicle for transforming inert C[BOND]H bonds in organic compounds to reactive C[BOND]metal bonds.1 Progress in metalation was accelerated greatly by the development of DoM (directed ortho-metalation),2 pioneered by Snieckus, Beak, and others, a special type of lithiation (aromatic C[BOND]H to Cδ−[BOND]Liδ+) reliant on the high polarity of carbon–lithium bonds in organolithium reagents. Many other metals could not engage in metalation due to the lower polarity/lower reactivity of their corresponding carbon–metal bonds. However, this obstacle has now been cleared by the recognition that when part of a mixed-metal system or other multicomponent mixture, these metals (for example, magnesium, zinc, aluminum or manganese) can exhibit greatly enhanced metalating properties often superior in terms of functional-group compatibility or reaction conditions to that of lithium. Interest in these new “low polarity” metalating agents is widespread with coverage in fundamental chemistry journals,3 process chemistry journals,4 interdisciplinary science journals,5 and in news items in scientific media.6 Knochel’s turbo-Grignard reagents (e.g., (iPr)MgCl⋅LiCl) 7 are examples that have been commercialized. A spectacular demonstration of the special reactivity of bimetallic bases came with the α-zincation of tetrahydrofuran (THF) by the sodium dialkyl(amido)zincate [(TMEDA)Na(μ-TMP)(μ-CH2SiMe3)Zn(CH2SiMe3)] (TMEDA=N,N,N′,N′-tetramethylethylenediamine; TMP=2,2,6,6-tetramethylpiperidine) to produce [(TMEDA)Na(μ-TMP)(μ-OC4H7)Zn(CH2SiMe3)].5 Conventional metalation of THF invariably initiates decomposition by ring opening,8 but in this low-polarity zincation the 5-atom ring of the sensitive α-deprotonated THF anion remains intact. However, this reaction is extremely slow (best yield was 52.7 % after 2 weeks) and requires a massive stoichiometric excess of the cyclic ether (i.e., carried out in neat THF solvent). Here we report a vastly superior methodology to the cyclic THF α-anion, mediated by a lithium aluminate base with a higher amido content than the alkyl-rich zincate reagent. An analogous reaction with the sulfur analogue, tetrahydrothiophene (THTP), is also reported.

Molecular Structures of THF‐Solvated Alkali‐Metal 2,2,6,6‐Tetramethylpiperidides Finally Revealed: X‐ray Crystallographic, DFT, and NMR (including DOSY) Spectroscopic Studies

The often studied THF solvates of the utility alkali-metal amides lithium and sodium 2,2,6,6-tetramethylpiperidide are shown to exist in the solid state as asymmetric cyclic dimers containing a central M(2)N(2) ring and one molecule of donor per metal to give a distorted trigonal planar metal coordination. DFT studies support these structures and confirm the asymmetry in the ring. In C(6)D(12) solution, the lithium amide displays a concentration-dependent equilibrium between a solvated and unsolvated species which have been shown by diffusion-ordered NMR spectroscopy (DOSY) to be a dimer and larger oligomer, respectively. A third species, a solvated monomer, is also present in very low concentration, as proven by spiking the NMR sample with THF. In contrast, the sodium amide displays a far simpler C(6)D(12) solution chemistry, consistent with the solid-state dimeric arrangement but with labile THF ligands.

Direct C-H metalation with chromium(ii) and iron(ii) : transition-metal host/benzenediide guest magnetic inverse-crown complexes

Abstract Check M(etal)ate: The chessboard and the figures represent a special reaction in which different low-polarity metals can metalate arenes directly when they are brought into the right position. In a combination of queen (sodium) and knight (chromium or iron), it is possible for the knight (usually the weaker piece) to make a direct deadly hit on the king (benzene) in this game of elemental chess.

Expanding Mg–Zn Hybrid Chemistry: Inorganic Salt Effects in Addition Reactions of Organozinc Reagents to Trifluoroacetophenone and the Implications for a Synergistic Lithium–Magnesium–Zinc Activation

Numerous organic transformations rely on organozinc compounds made through salt-metathesis (exchange) reactions from organolithium or Grignard reagents with a suitable zinc precursor. By combining X-ray crystallography, NMR spectroscopy and DFT calculations, this study sheds new light on the constitution of the organometallic species involved in this important synthetic tool. Investigations into the metathesis reactions of equimolar amounts of Grignard reagents (RMgX) and ZnCl(2) in THF led to the isolation of novel magnesium-zinc hybrids, [{(thf)(2)Mg(μ-Cl)(3)ZnR}(2)] (R=Et, tBu, nBu or o-OMe-C(6)H(4)), which exhibit an unprecedented structural motif in mixed magnesium-zinc chemistry. Furthermore, theoretical modelling of the reaction of EtMgCl with ZnCl(2) reveals that formation of the mixed-metal compound is thermodynamically preferred to that of the expected homometallic products, RZnCl and MgCl(2). This study also assesses the alkylating ability of hybrid 3 towards the sensitive ketone trifluoroacetophenone, revealing a dramatic increase in the chemoselectivity of the reaction when LiCl is introduced as an additive. This observation, combined with recent related breakthroughs in synthesis, points towards the existence of a trilateral Li/Mg/Zn synergistic effect.

Diaminogermylene and diaminostannylene derivatives of gold(I): novel AuM and AuM2 (M = Ge, Sn) complexes.

The reactions of [AuCl(THT)] (THT = tetrahydrothiophene) with 1 equiv of the group 14 diaminometalenes M(HMDS)(2) [M = Ge, Sn; HMDS = N(SiMe(3))(2)] lead to [Au{MCl(HMDS)(2)}(THT)] [M = Ge (1), Sn (2)], which contain a metalate(II) ligand that arises from insertion of the corresponding M(HMDS)(2) reagent into the Au-Cl bond of the gold(I) reagent. While compound 1 reacts with more Ge(HMDS)(2) to give the germanate-germylene derivative [Au{GeCl(HMDS)(2)}{Ge(HMDS)(2)}] (3), which results from substitution of Ge(HMDS)(2) for the THT ligand of 1, an analogous treatment of compound 2 with Sn(HMDS)(2) gives the stannate-stannylene derivative [Au{SnCl(HMDS)(2)}{Sn(HMDS)(2)(THT)}] (4), which has a THT ligand attached to the stannylene tin atom and which, in solution at room temperature, participates in a dynamic process that makes its two Sn(HMDS)(2) fragments equivalent (on the NMR time scale). A similar dynamic process has not been observed for the AuGe(2) compound 3 or for the AuSn(2) derivatives [Au{SnR(HMDS)(2)}{Sn(HMDS)(2)(THT)}] [R = Bu (5), HMDS (6)], which have been prepared by treating complex 4 with LiR. The structures of compounds 1 and 3-6 have been determined by X-ray diffraction.

Structural tracking of the potassium-mediated magnesiation of anisole.

The potassium-mediated magnesiation of anisole has been monitored by a combination of X-ray crystallographic and NMR spectroscopic studies. Departing from a heteroleptic alkyl-amido base and anisole, the reaction first stops at an ortho-magnesiated anisole intermediate, but the final destination is an ortho-magnesiated anisole complex with reincorporation of the amine ligand and elimination of alkane (see picture).