Tuning NaCo(II) Bimetallic Cooperativity to Perform Co-H Exchange / C-F Bond Activation Processes in Polyfluoroarenes.

Recent advances in cooperative chemistry have shown the potential of heterobimetallic complexes combining an alkali-metal with an earth abundant divalent transition metal for the functionalisation of synthetically relevant aromatic molecules via deprotonative metalation. Pairing sodium with cobalt (II), here we provide an overview of the reactivity of bimetallic [NaCo(HMDS)3] [HMDS = N(SiMe3)2] towards C-H and C-F functionalisation of a wide range of perfluorinated molecules. These studies also uncover the enormous potential of this heterobimetallic base to perform Co-H exchanges with excellent selectivity and exceptional stoichiometric control as well as shedding light on the key role played by the alkali-metal.

The coordination of alkali-metal nickelates to organic π-systems: synthetic, structural and spectroscopic insights.

Low-valent nickelates have recently been shown to be key intermediates in challenging cross-coupling reactions using aryl ethers as electrophiles. Key for the success of these transformations is the activation of the substrate through π-coordination to the nickelate intermediate, however there is still limited knowledge about the fundamental structure and coordination chemistry of these heterobimetallic complexes. Herein, we report the synthesis, structures, and spectroscopic analysis of a diverse family of alkali-metal nickelates derived from phenyl-alkali-metal reagents and Ni(ttt-CDT), where ttt-CDT = trans,trans,trans-1,5,9-cyclododecatriene. The co-complexation of PhLi with Ni(ttt-CDT) was found to yield 1 : 1, 2 : 1 or 4 : 2 lithium nickelates depending on the stoichiometry and reaction conditions employed. The high lability of the ttt-CDT ligand enables facile ligand exchange with an assorted series of organic π-acceptors, ranging from polyaromatic hydrocarbons to ketones, imines and nitriles. For anthracene and phenanthrene, a homologous series of Li, Na and K nickelates could be obtained, which lead to different structural motifs or degrees of aggregation in the solid-state spanning solvated monomers to complex polymeric arrangements. For π-extended systems such as perylene or coronene, competing single-electron-transfer to give the corresponding radical anions was observed, illustrating the highly reducing nature of the alkali-metal nickelates. X-ray crystallographic analysis and NMR spectroscopy of the phenyl-alkali-metal nickelates reveal extreme back-bonding from Ni(0) to the organic π-acceptors due to strong σ-donation from the carbanionic ligands.

Unlocking the Metalation Applications of TMP-powered Fe and Co(II) bis(amides): Synthesis, Structure and Mechanistic Insights.

Typified by LiTMP and TMPMgCl.LiCl, (TMP=2,2,6,6-tetramethylpiperidide), s-block metal amides have found widespread applications in arene deprotonative metalation. On the contrary, transition metal amides lack sufficient basicity to activate these substrates. Breaking new ground in this field, here we present the synthesis and full characterisation of earth-abundant transition metals M(TMP)2 (M=Fe, Co). Uncovering a new reactivity profile towards fluoroarenes, these amide complexes can promote direct M-H exchange processes regioselectively using one or two of their basic amide arms. Remarkably, even when using a perfluorinated substrate, selective C-H metalation occurs leaving C-F bonds intact. Their kinetic basicity can be boosted by LiCl or NBu4Cl additives which enables formation of kinetically activated ate species. Combining spectroscopic and structural studies with DFT calculations, mechanistic insights have been gained on how these low polarity metalation processes take place. M(TMP)2 can also be used to access ferrocene and cobaltocene by direct deprotonation of cyclopentadiene and undergo efficient CO2 insertion of both amide groups under mild reaction conditions.

Dual Basicity and Nucleophilicity of Organosodium Reagents in Benzylic C-H Additions of Toluenes to Diarylethenes and Ketones.

Profiting from the dual high basicity and nucleophilicity of organosodium complexes, here we report the stepwise lateral metalation of a wide range of alkyl arenes (MeAr), mediated by hydrocarbon-soluble NaCH2SiMe3.PMDETA (PMDETA = N,N,N',N'',N''-pentamethyldiethylenetriamine), followed by nucleophilic addition to olenfins of the newly generated NaCH2Ar.PMDETA complexes. This method grants access to a range of functionalised hydrocarbons in excellent yields and can be upgraded to catalytic regimes when using trans-stilbene, a 10 mol% of the alkyl sodium base and toluene as a solvent. Extending this approach to aromatic ketones leads to the formation of stilbenes under mild reaction conditions, resulting from the deprotonative coupling of toluenes with ketones. Combining spectroscopic studies with the trapping and characterisation of key reaction intermediates, mechanistic insights have been gained, advancing the understanding of coordination effects in organosodium chemistry, and shedding light on their special reactivity profiles.

Stoichiometric and Catalytic Lithium Nickelate-Mediated C-F Bond Alkynylation of Fluoroarenes.

Low-valent nickelates have recently been shown to be key intermediates that facilitate challenging cross-coupling reactions under mild conditions. Expanding the synthetic potential of these heterobimetallic complexes, herein we report the success of trilithium nickelate Li3(TMEDA)3Ni(C≡C-Ph)3 in promoting stoichiometric C-F activation of assorted aryl fluorides furnishing novel mixed Li/Ni(0) or Li/Ni(II) species depending on the substrate and conditions employed. These stoichiometric successes can be upgraded to catalytic regimes to enable the atom-efficient alkynylation of aryl fluorides and polyfluoroarenes with lithium acetylides and precatalyst Ni(COD)2, which operates without the intervention of external ligands, Cu cocatalysts, or additives.

Synthesis and Modular Reactivity of Low Valent Al/Zn Heterobimetallics Supported by Common Monodentate Amides.

Recent advances on low valent main group metal chemistry have shown the excellent potential of heterobimetallic complexes derived from Al(I) to promote cooperative small molecule activation processes. A signature feature of these complexes is the use of bulky chelating ligands which act as spectators providing kinetic stabilization to their highly reactive Al-M bonds. Here we report the synthesis of novel Al/Zn bimetallics prepared by the selective formal insertion of AlCp* into the Zn-N bond of the utility zinc amides ZnR2 (R=HMDS, hexamethyldisilazide; or TMP, 2,2,6,6-tetramethylpiperidide). By systematically assessing the reactivity of the new [(R)(Cp*)AlZn(R)] bimetallics towards carbodiimides, structural and mechanistic insights have been gained on their ability to undergo insertion in their Zn-Al bond. Disclosing a ligand effect, when R=TMP, an isomerization process can be induced giving [(TMP)2AlZn(Cp*)] which displays a special reactivity towards carbodiimides and carbon dioxide involving both its Al-N bonds, leaving its Al-Zn bond untouched.

New Frontiers in Organosodium Chemistry as Sustainable Alternatives to Organolithium Reagents.

With their highly reactive respective C-Na and N-Na bonds, organosodium and sodium amide reagents could be viewed as obvious replacements or even superior reagents to the popular, widely utilised organolithiums. However, they have seen very limited applications in synthesis due mainly to poor solubility in common solvents and their limited stability. That notwithstanding in recent years there has been a surge of interest in bringing these sustainable metal reagents into the forefront of organometallics in synthesis. Showcasing the growth in utilisation of organosodium complexes within several areas of synthetic chemistry, this Minireview discusses promising new methods that have been recently reported with the goal of taming these powerful reagents. Special emphasis is placed on coordination and aggregation effects in these reagents which can impart profound changes in their solubility and reactivity. Differences in observed reactivity between more nucleophilic aryl and alkyl sodium reagents and the less nucleophilic but highly basic sodium amides are discussed along with current mechanistic understanding of their reactivities. Overall, this review aims to inspire growth in this exciting field of research to allow for the integration of organosodium complexes within common important synthetic transformations.

Uncovering the Untapped Potential of the Use of Sodium Amides for Regioselective Arene Functionalisation.

Alkali-metal amides have become key reagents in synthetic chemistry, with special focus in deprotonation reactions. Despite the higher reactivity found in the heavier sodium and potassium amides, their insolubility and low stability has favoured the use of the more soluble  lithium analogues, converting them into the most used non-nucleophilic bases. Studying the coordination effects of Lewis donor molecules such as tridentate amine PMDETA (N,N,N',N'',N''-pentamethyldiethylenetriamine) in combination with the sodium amide NaTMP (TMP = 2,2',6,6'-tetramethylpiperidide), we have been able to unlock the use of these reagents for the functionalisation of arenes, i.e. the deuterium incorporation by hydrogen isotope exchange and the deprotonative borylation of unactivated arenes. These findings show how sodium amides are not just a simple more sustainable replacement of their lithium counterparts, but also that they can display significantly enhanced reactivities allowing for the development of new transformations.

New Frontiers in Alkali-Metal Nickelates.

Recent advances in heterobimetallic chemistry have revealed the potential for mixed-metal systems to facilitate reactions that are unattainable with their single-metal components. This perspective explores the pairing of nickel(0) complexes with organo-alkali-metal reagents, which yield highly reactive alkali-metal nickelates. These previously underexplored systems have re-emerged as a promising area of research, with recent studies uncovering their unique bonding and structural motifs. Furthermore, the discovery of nickelates as potential intermediates in cross-coupling reactions has provided the foundation for the development and mechanistic understanding of stoichiometric and catalytic transformations.

Alkali-metal bases in catalytic hydrogen isotope exchange processes.

The preparation of compounds labelled with deuterium or tritium has become an essential tool in a range of research fields. Hydrogen isotope exchange (HIE) offers direct access to said compounds, introducing these isotopes in a late stage. Even though the field has rapidly advanced with the use of transition metal catalysis, alkali-metal bases, used as catalysts or under stoichiometric conditions, have also emerged as a viable alternative. In this minireview we describe the latest advances in the use of alkali-metal bases in HIE processes, showcasing their synthetic potential as well as current challenges in the field. It is divided in different sections based on the isotope source used, emphasizing their benefits, disadvantages and limitations. The influence on the choice of alkali-metal in these processes as well as their possible mechanistic pathways are also discussed.

Main group metal-mediated strategies for C-H and C-F bond activation and functionalisation of fluoroarenes.

With fluoroaromatic compounds increasingly employed as scaffolds in agrochemicals and active pharmaceutical ingredients, the development of methods which facilitate regioselective functionalisation of their C-H and C-F bonds is a frontier of modern synthesis. Along with classical lithiation and nucleophilic aromatic substitution protocols, the vast majority of research efforts have focused on transition metal-mediated transformations enabled by the redox versatilities of these systems. Breaking new ground in this area, recent advances in main group metal chemistry have delineated unique ways in which s-block, Al, Ga and Zn metal complexes can activate this important type of fluorinated molecule. Underpinned by chemical cooperativity, these advances include either the use of heterobimetallic complexes where the combined effect of two metals within a single ligand set enables regioselective low polarity C-H metalation; or the use of novel low valent main group metal complexes supported by special stabilising ligands to induce C-F bond activations. Merging these two different approaches, this Perspective provides an overview of the emerging concept of main-group metal mediated C-H/C-F functionalisation of fluoroarenes. Showcasing the untapped potential that these systems can offer in these processes; focus is placed on how special chemical cooperation is established and how the trapping of key reaction intermediates can inform mechanistic understanding.

Shedding Light on the Hidden Roles of Lithium in the Nickel-Catalyzed Cross-Coupling of Aryl Ethers.

The Ni-catalyzed cross-coupling of aryl ethers is a powerful synthetic tool to transform widely available phenol derivatives into functionalized aromatic molecules. Recent theoretical and experimental mechanistic studies have identified the involvement of heterobimetallic nickelates as key intermediates that facilitate the challenging transformation under mild conditions and often without the need for external ligands or additives. In this work, based on calculations performed at the density functional theory (DFT) level and by comparison with spectroscopic and kinetic data, we investigate the mechanism of the Ni(COD)2-catalyzed cross-coupling of 2-methoxynaphthalene with PhLi and assess the speciation of lithium nickelate intermediates. The crucial role of solvent on the reaction is explained, and the multiple roles played by lithium are unveiled. Experimental studies have identified key lithium nickelate species which support and help to evolve the calculated reaction mechanism and ultimately complete the catalytic cycle. Based on this new mechanistic knowledge, a well-known experimental challenge of these transformations, the so-called "naphthalene problem" which restricts the use of electrophilic coupling partners to π-extended systems, can be addressed to enable the cross-coupling of unbiased aryl ethers under mild conditions.

Sodium mediated deprotonative borylation of arenes using sterically demanding B(CH2SiMe3)3: unlocking polybasic behaviour and competing lateral borane sodiation.

The deprotonative metalation of organic molecules has become a convenient route to prepare functionalised aromatic substrates. Amongst the different metallating reagents available, sodium bases have recently emerged as a more sustainable and powerful alternative to their lithium analogues. Here we report the study of the sterically demanding electrophilic trap B(CH2SiMe3)3 for the deprotonative borylation of arenes using NaTMP (TMP = 2,2,6,6-tetramethylpiperidide) in combination with tridentate Lewis donor PMDETA (PMDETA = N,N,N',N'',N''-pentamethyldiethylenetriamine). Using anisole and benzene as model substrates, unexpected polybasic behaviour has been uncovered, which enables the formal borylation of two equivalents of the relevant arene. The combination of X-ray crystallographic and NMR monitoring studies with DFT calculations has revealed that while the first B-C bond forming process takes place via a sodiation/borylation sequence to furnish [(PMDETA)NaB(Ar)(CH2SiMe3)3] species, the second borylation step is facilitated by the formation of a borata-alkene intermediate, without the need of an external base. For non-activated benzene, it has also been found that under stoichimetric conditions the lateral sodiation of B(CH2SiMe3)3 becomes a competitive reaction pathway furnishing a novel borata-alkene complex. Showing a clear alkali-metal effect, the use of the sodium base is key to access this reactivity, while the metalation/borylation of the amine donor PMDETA is observed instead when LiTMP is used.

Organolithium aggregation as a blueprint to construct polynuclear lithium nickelate clusters.

By exploiting the high aggregation of aliphatic lithium acetylides, here we report the synthesis and structural analysis of polynuclear lithium nickelate clusters in which up to 10 equivalents of organolithium can co-complex per Ni(0) centre. Exposure of the Ni(0)-ate clusters to dry air provides an alternative route to homoleptic Ni(II)-ates.

Atom-efficient arylation of N-tosylimines mediated by cooperative ZnAr2/Zn(C6F5)2 combinations.

By combining the Lewis acid Zn(C6F5)2 with nucleophilic diarylzinc (ZnAr2) reagents, we report the atom-efficient arylation of N-tosylimines under mild conditions. Mechanistic studies through the isolation of key intermediates reveal how the two zinc species act cooperatively to activate the imine substrate and regenerate the ZnAr2 reagent, enabling a limiting 50 mol% to be employed.

Applying Na/Co(II) bimetallic partnerships to promote multiple Co-H exchanges in polyfluoroarenes.

Heterobimetallic base NaCo(HMDS)3 [HMDS = N(SiMe3)2] enables regioselective di-cobaltation of activated polyfluoroarenes under mild reaction conditions. For 1,3,5-C6H2X3 (X= Cl, F), NaCo(HMDS)3 in excess at 80 °C impressively induces the collective cleavage of five bonds (two C-H and three C-X) of the substrates via a cascade activation process that cannot be replicated by LiCo(HMDS)3 or KCo(HMDS)3.

Structural and Synthetic Insights on Oxidative Homocouplings of Alkynes Mediated by Alkali-Metal Manganates.

Exploiting bimetallic cooperation alkali-metal manganate (II) complexes can efficiently promote oxidative homocoupling of terminal alkynes furnishing an array of conjugated 1,3-diynes. The influence of the alkali-metal on these C-C bond forming processes has been studied by preparing and structurally characterizing the alkali-metal tetra(alkyl) manganates [(TMEDA)2 Na2 Mn(CH2 SiMe3 )4 ] and [(PMDETA)2 K2 Mn(CH2 SiMe3 )4 ]. Reactivity studies using phenylacetylene as a model substrate have revealed that for the homocoupling to take place initial metalation of the alkyne is required. In this regard, the lack of basicity of neutral Mn(CH2 SiMe3 )2 precludes the formation of the diyne. Contrastingly, the tetra(alkyl) alkali-metal manganates behave as polybasic reagents, being able to easily deprotonate phenylacetylene yielding [{(THF)4 Na2 Mn(C≡CPh)4 }∞ ] and [(THF)4 Li2 Mn(C≡CPh)4 ]. Controlled exposure of [{(THF)4 Na2 Mn(C≡CPh)4 }∞ ] and [(THF)4 Li2 Mn(C≡CPh)4 ] to dry air confirmed their intermediary in formation of 1,4-diphenyl-1,3-butadiyne in excellent yields. While the Na/Mn(II) partnership proved to be the most efficient in stoichiometric transformations, under catalytic regimes, the combination of MC≡CAr (M= Li, Na) and MnCl2 (6 mol %) only works for lithium, most likely due to the degradation of alkynylsodiums under the aerobic reaction conditions.

Alkali-Metal-Alkoxide Powered Zincation of Fluoroarenes Employing Zinc Bis-Amide Zn(TMP)2.

Reminiscent of Lochmann-Schlosser superbase recipes, the addition of two molar equivalents of KOtBu to Zn(TMP)2 (TMP=2,2,6,6-tetramethylpiperidide) transforms this mild zinc bis-amide base to a powerful metalating agent able to perform facile regioselective zincation of a wide range of sensitive fluoroarenes. Structural authentication of the intermediates post Zn-H exchange demonstrates activation of both TMP groups to form a range of higher order bis-aryl potassium zincates, isolable as solids and further functionalized in electrophilic interception reactions. Studies assessing the role of KOtBu reveal that the first equivalent undergoes co-complexation with Zn(TMP)2 , enabling kinetic activation of the amide groups; whereas the second equivalent stabilizes the metalated intermediate preventing ligand redistribution. Showcasing its metalating power, this bimetallic KOtBu/Zn(TMP)2 partnership, can effect zincation of toluene and benzene at room temperature.