Metal-ligand Cooperation Research Articles

Selective Cobalt-Mediated Formation of Hydrogen Peroxide from Water under Mild Conditions via Ligand Redox Non-Innocence.

Despite the broad importance of hydrogen peroxide (H2O2) in oxidative transformations, there are comparatively few viable routes for its production. The majority of commercial H2O2 is currently produced by the stepwise reduction of dioxygen (O2) via the anthraquinone process, but direct electrochemical formation from water (H2O) would have several advantages─namely, avoiding flammable gases or stepwise separations. However, the selective oxidation of H2O to form H2O2 over the thermodynamically favored product of O2 is a difficult synthetic challenge. Here, we present a molecular H2O oxidation system with excellent selectivity for H2O2 that functions both stoichiometrically and catalytically. We observe high efficiency for electrocatalytic H2O2 production at low overpotential with no O2 observed under any conditions. Mechanistic studies with both calculations and kinetic analyses from isolated intermediates suggest that H2O2 formation occurs in a bimolecular fashion via a dinuclear H2O2-bridged intermediate with an important role for a redox non-innocent ligand. This system showcases the ability of metal-ligand cooperativity and strategic design of the secondary coordination sphere to promote kinetically and thermodynamically challenging selectivity in oxidative catalysis.

Synthesis and Reactivity of an Aluminium N-heterocyclic Aminal.

Tethered N-heterocyclic carbenes (NHCs) are an emerging class of ligand, as they feature all the desirable aspects of NHCs (ease of synthesis, high tunabilty) but also enable metal-ligand cooperativity when combined with Lewis acidic metal centres due to the donor-acceptor nature of the complexes formed. Herein we report a simple ethoxy-tethered NHC for the stabilisation of Al(III) hydrides, resulting in the unexpected formation of a bicyclic N-heterocyclic aminal (1). Compound 1 behaves as a metal hydride, capable of reducing benzophenone and carbodiimide to yield compounds 2 and 3, respectively. Furthermore, we show that 1 behaves as an efficient catalyst in the dehydrocoupling of amine-boranes due to the hemi-labile nature of the supporting ligand.

Tautomerism vs lone pair metal ligand cooperation in selective Mn-PNN catalyzed hydrogenation of amides

Metal-ligand cooperation (MLC) is an important strategy in transition-metal (TM) catalysis. Tautomerism-driven MLC has recently been emerging as a novel type of catalyst design strategy. However, the difference between the conventional lone-pair-driven MLC and tautomerism-driven MLC in mechanism and selectivity remains unclear. Herein, a DFT study was performed to unveil the difference between them in the (iPrPHNN)Mn catalyzed selective hydrogenation of amide. The double deprotonated (iPrPHNN)Mn could lead to an active species with two functional sites, i.e., the N site and the C site, which would promote the lone-pair-driven MLC and the tautomerism-driven MLC for the catalytic hydrogenation, respectively. Systematic investigation of the full catalytic cycles, including hemiaminal formation, hydrogenation of amide, and the generation of alcohol and amine, reveals that the addition of H2 onto amide prefers the lone-pair-driven MLC mechanism assisted by a proton shuttle. Then, the formed hemiaminal intermediate would competitively undergo the C-O bond cleavage to the secondary amine product or the C-N bond cleavage to the primary amine and alcohol products. Both the C-N bond cleavage and the C-O bond cleavage prefer the tautomerism-driven MLC, with the free energy barrier of the former being lower than that of the latter by around 12 kcal/mol. In the tautomerism-driven MLC mechanism, the lone-pair electrons on the innocent amido would increase the electron density of the metal center, which would lead to an easier electron transfer from the Mn center to the substrate, causing the favorable cleavage of the C-N bond. In the following hydrogenation step, the generation of aldehyde to alcohol or the hydrogenation of imine to amine can occur via either the lone-pair-driven MLC or the tautomerism-driven MLC. The driving force of the tautomerism-driven MLC is of key importance for selectivity. The results of the lone-pair-driven MLC and the tautomerism-driven MLC mechanisms in selectivity would be helpful for the design of MLC catalysis.

Nickel-Catalyzed Chemodivergent Coupling of Alcohols: Efficient Routes to Access α,α-Disubstituted Ketones and α-Substituted Chalcones.

Chemodivergent (de)hydrogenative coupling of primary and secondary alcohols is achieved utilizing an inexpensive nickel catalyst, (6-OH-bpy)NiCl2 . This protocol demonstrates the synthesis of branched carbonyl compounds, α,α-disubstituted ketones, and α-substituted chalcones via borrowing hydrogen strategy and acceptorless dehydrogenative coupling, respectively. A wide range of aryl-based secondary alcohols are coupled with various primary alcohols in this tandem dehydrogenation/hydrogenation reaction. The nickel catalyst, along with KOt Bu or K2 CO3 , governed the selectivity for the formation of branched saturated ketones or chalcones. A preliminary mechanistic investigation confirms the reversible dehydrogenation of alcohols to carbonyls via metal-ligand cooperation (MLC) and the involvement of radical intermediates during the reaction.

Metal–Ligand Cooperative Catalytic Coupling of Terminal Alkynes and Carboxylic Acids for the Stereoselective Synthesis of Dienyl Esters

Metal–Ligand Cooperative Catalytic Coupling of Terminal Alkynes and Carboxylic Acids for the Stereoselective Synthesis of Dienyl Esters

Designing Cobalt(II) Complexes for Tandem Dehydrogenative Synthesis of Quinoline and Quinazoline Derivatives.

In this work, we have constructed three new Co(II) complexes in which steric features govern their structural geometry. The metal ligand-cooperation behavior of the alkoxy arm is utilized to explore the catalytic activities of these complexes with respect to dehydrogenation. A wide range of C-3-substituted quinoline and quinazoline derivatives were synthesized in high yields. The developed protocol's usefulness is enhanced by the chemoselective transformation of different fatty alcohols to synthesize heterocycles having distal unsaturation. Various kinetic, mechanistic, and control studies were conducted to comprehend the reaction route.

Metal-Tuned Ligand Reactivity Enables CX2 (X = O, S) Homocoupling with Spectator Cu Centers.

Ligand non-innocence is ubiquitous in catalysis with ligands in synthetic complexes contributing as electron reservoirs or co-sites for substrate activation. The latter chemical non-innocence is manifested in H+ storage or relay at sites beyond the metal primary coordination sphere. Reaction of a competent CO2-to-oxalate reduction catalyst, namely, [K(THF)3](Cu3SL), where L3- is a tris(β-diketiminate) cyclophane, with CS2 affords tetrathiooxalate at long reaction times or at high CS2 concentrations, where otherwise an equilibrium is established between the starting species and a complex-CS2 adduct in which the CS2 is bound to the C atom on the ligand backbone. X-ray diffraction analysis of this adduct reveals no apparent metal participation, suggesting an entirely ligand-based reaction controlled by the charge state of the cluster. Thermodynamic parameters for the formation of the aforementioned Cligand-CS2 bond were experimentally determined, and trends with cation Lewis acidity were studied, where more acidic cations shift the equilibrium toward the adduct. Relevance of such an adduct in the reduction of CO2 to oxalate by this complex is supported by DFT studies, similar effects of countercation Lewis acidity on product formation, and the homocoupled heterocumulene product speciation as determined by isotopic labeling studies. Taken together, this system extends chemical non-innocence beyond H+ to effect catalytic transformations involving C-C bond formation and represents the rarest example of metal-ligand cooperativity, that is, spectator metal ion(s) and the ligand as the reaction center.

Unlocking the potential of metal ligand cooperation for enantioselective transformations.

Metal-ligand cooperation, in which both the metal and the ligand of a transition metal complex actively participate in chemical transformations leading to enhanced reactivity or selectivity in chemical reactions, has emerged as a powerful and versatile concept in catalysis. This Viewpoint discusses the development trajectory of transition metal-based complexes as catalysts in (de)hydrogenative processes, in particular those cases where metal-ligand cooperation has been invoked to rationalise the observed high reactivities and excellent selectivities. The historical context, mechanistic aspects and current applications are discussed with the suggestion to explore the potential of the MLC mode of action of such catalysts in enantioselective transformations beyond (de)hydrogenative processes.

Cobalt-catalyzed double hydroboration of pyridines.

Cobalt(ii) complexes were prepared from a modular phosphinopyridonate platform and applied to the hydroboration of pyridines. The synthetically useful, yet challenging, double hydroboration toward tetrahydropyridine derivatives was successfully performed with high activity and regiocontrol. This new method enabled the direct synthesis of N-heterocyclic allylic boronates from commercial pyridines and pinacolborane (HBpin). One-pot acetylation afforded the bench-stable borylated N-acetyl tetrahydropyridines in good yields. The synthetic utility of this procedure was demonstrated by a gram-scale double hydroboration-acetylation sequence followed by chemical diversification. Mechanistic experiments indicated metal-ligand cooperativity involving ligand-centered C-H activation and the intermediacy of a cobalt(iii) hydride species.

NHC–amine Ru complex catalyzed selective mono-N-methylation of amines with methanol: understanding the effect of amine ligands

The selective mono-N-methylation of amines with methanol by the bifunctional NHC–NH2 Ru complex is presented.

Leveraging ligand-based proton and electron transfer for aerobic reactivity and catalysis.

While O2 is an abundant, benign, and thermodynamically potent oxidant, it is also kinetically inert. This frequently limits its use in synthetic transformations. Correspondingly, direct aerobic reactivity with O2 often requires comparatively harsh or forcing conditions to overcome this kinetic barrier. Forcing conditions limit product selectivity and can lead to over oxidation. Alternatively, O2 can be activated by a catalyst to facilitate oxidative reactivity, and there are a variety of sophisticated examples where transition metal catalysts facilitate aerobic reactivity. Many efforts have focused on using metal-ligand cooperativity to facilitate the movement of protons and electrons for O2 activation. This approach is inspired by enzyme active sites, which frequently use the secondary sphere to facilitate both the activation of O2 and the oxidation of substrates. However, there has only recently been a focus on harnessing metal-ligand cooperativity for aerobic reactivity and, especially, catalysis. This perspective will discuss recent efforts to channel metal-ligand cooperativity for the activation of O2, the generation and stabilization of reactive metal-oxygen intermediates, and oxidative reactivity and catalysis. While significant progress has been made in this area, there are still challenges to overcome and opportunities for the development of efficient catalysts which leverage this biomimetic strategy.

A sustainable strategic approach for N-alkylation of amines with activation of alcohols triggered via a hydrogen auto-transfer reaction using a Pd(II) complex: evidence for metal-ligand cooperativity.

This work describes a new well-defined, air-stable, phosphine free palladium(II) [Pd(L)Cl] (1) catalyst. This catalyst was utilized for N-alkylation of amines and indole synthesis where H2O was found to be the by-product. A broad range of aromatic amines were alkylated using this homogeneous catalyst with a catalyst loading of 0.1 mol%. Greener aromatic and aliphatic primary alcohols were utilized and a hydrogen auto-transfer strategy via a metal-ligand cooperative approach was investigated. The precursor of the antihistamine-containing drug molecule tripelennamine was synthesized on a gram scale for large-scale applicability of the current synthetic methodology. A number of control experiments were performed to investigate the possible reaction pathway and the outcomes of these experiments indicated the azo-chromophore as a hydrogen reservoir during the catalytic cycle.

Nitrogen monoxide and calix[4]pyrrolato aluminate: structural constraint enabled NO dimerization.

The dimerization of nitrogen monoxide (NO) is highly relevant in homo- and heterogeneous biochemical and environmental redox processes, but a broader understanding is challenged by the endergonic nature of this equilibrium. The present work describes NO-dimerization leveraged by structurally constrained aluminum and metal-ligand cooperativity at the anionic calix[4]pyrrolato aluminate(III). Quantum chemical calculations reveal the driving force for N-N bond formation, while reactivity tests shed light on subsequent redox chemistry and NO decomposition at metal surfaces. Inhibiting the dimerization pathway by saturating NO's unpaired electron with a phenyl group (nitrosobenzene) allows trapping the 1,2-adduct as a key intermediate. Elevated temperatures result in an unprecedented and high-yielding rearrangement of the calix[4]pyrrolato ligand scaffold. Kinetic and theoretical studies provide a comprehensive picture of the rearrangement mechanism and delineate systematics for ring modification of the prominent calix[4]pyrrole macrocycle.

Quantifying variation in cooperative B-H bond activations using Os(ii) and Os(iii) κ2-N,S-chelated complexes: same, but different.

In an effort to investigate small molecule activation by heavier transition metal (TM) based κ2-N,S-chelated species, we have synthesised a series of bis-κ2-1,3-N,S-chelated complexes of osmium, [Os(PPh3)2(κ2-N,S-La/Lb)2], 2a-b, and [Os(PPh3)(La/Lb)(κ2-N,S-La/Lb)2], 3a-b (2a and 3a: La[double bond, length as m-dash] = C7H4NS2; 2b and 3b: Lb = C5H4NS), from the thermolysis of [Os(PPh3)3Cl2], 1, with a potassium salt of heterocyclic ligands La and Lb. The former complexes are diamagnetic in nature, while the EPR spectra, XPS study and density functional theory (DFT) calculations have substantiated the paramagnetic behaviour of 3a-b with a significant spin contribution from non-innocent ligands. These species were engaged in B-H activation of boranes utilizing the combined effect of hemilability and metal-ligand cooperativity (MLC), where 2a-b upon treatment with BH3·SMe2 yielded Os(σ-borate)hydride complexes, [Os(PPh3)2(H){κ3-H,S,S'-BH2(La/Lb)2}], 4a-b (4a: La = C7H4NS2; 4b: Lb = C5H4NS). The formation of 4a-b was emphasized on the basis of possible dual B-H activation that involved a few concerted steps, i.e., (i) cleavage of one hemilabile Os-N bond and cooperative B-H bond activation, (ii) cleavage of another hemilabile Os-N bond and formation of a B-N bond and (iii) activation of another B-H bond. In stark contrast, the paramagnetic bis-κ2-1,3-N,S-chelated species 3a-b manifested diverse activation patterns in the light of the different electronic nature of non-innocent ligands. While the reaction of 3b with borane generated dihydridoborate species, [Os(PPh3)(κ2-N,S-Lb)(κ3-H,H,S'-BH2(OH)C5H4NS)], 5, complex 3a led to the formation of an Os(σ-borate) complex, [Os(PPh3)(κ2-N,S-La)(κ3-H,S,S'-BH2L2 a)], trans-6. As the σ-borate entity shows a tendency to adapt to different spatial arrangements around the metal center, we have established a modified synthetic strategy to isolate the cis isomer of 6 that involved the reaction of [Os(PPh3)3Cl2], 1, with NaBH2La 2. In a similar fashion, the treatment of [Os(PPh3)3Cl2], 1, with NaBH2Lb 2 yielded [Os(PPh3)(κ2-N,S-Lb)(κ3-H,S,S'-BH2L2 b)], cis-7. The kinetic and thermodynamic stability of these isomeric species were investigated on the basis of extensive density functional theory (DFT) calculations. Theoretical calculations also provided insightful information on the electronic nature of the species, generated from B-H activations of boranes.

ZnCl2-catalysed transfer hydrogenation of carbonyls and chemoselective reduction of the CC bond in α,β-unsaturated ketones.

This manuscript describes chemoselective reduction of CC in α,β-unsaturated ketones and the transfer hydrogenation of aldehydes and ketones catalysed by ZnCl2-phosphinamino-triazolyl-pyridine (0.5 mol%) using KOH/iPrOH as a H2 source. A detailed mechanistic study using DFT calculations (B3LYP-D3/def2-TZVP) revealed the key role of metal-ligand cooperation (MLC) in the catalytic reaction demonstrating the non-innocent behaviour of the phosphine ligand.

Ester hydrogenolysis via β-C-O bond cleavage catalysed by a phenanthroline-based PNNP-cobalt(I) complex.

A Co(I) catalyst bearing a phenanthroline-based PNNP ligand (2,9-bis((diphenylphosphanyl)methyl)-1,10-phenanthroline) exhibits long-range metal ligand cooperation behavior using a ligand backbone as a hydrogen reservoir and catalyses hydrogenolysis of benzyl benzoate derivatives via β-C-O cleavage with atmospheric pressure H2.

CuI-amidobis(phosphine) catalyzed C(sp3)-C(sp3) direct homo- and hetero-coupling of unactivated alkanes via C(sp3)-H activation.

Herein, we present a CuI-dimer, [CuI{Ph2PC6H4C(O)NC6H4PPh2-o}]2, which catalyzed direct C(sp3)-H homocoupling of benzyl and cycloalkane derivatives with excellent yields and regio-selectivity. The method is very simple and tolerates various functionalities. Synergistic metal-ligand cooperativity was observed in Cu-N bond cleavage and protonation of nitrogen, and facilitates a bifunctional pathway, minimising the free energy corrugation for catalytic intermediates.

A catalytic collaboration: pairing transition metals and Lewis acids for applications in organic synthesis.

The use of metal catalysts to accelerate an organic transformation has proven indispensable for access to structural motifs having applications across medicinal, polymer, materials chemistry, and more. Most catalytic approaches have cast transition metals in the "leading role"; these players mediate important reactions such as C-C cross coupling and the hydrogenation of unsaturated bonds. These catalysts may require collaboration, featuring Lewis acidic or basic additives to promote a desired reaction outcome. Lewis acids can serve to accelerate reactions by way of substrate stabilization and/or activation, and as such, are valuable in optimizing catalytic transformations. A burgeoning area of chemical research which unifies these concepts has thus sought to develop transition metal complexes having ambiphilic (containing a Lewis basic and acidic unit) ligands. This approach takes advantage of metal-ligand cooperativity to increase the efficiency of a given chemical transformation, leveraging intramolecular interactions between a transition metal and an adjacent secondary ligand site. While this has shown significant potential to facilitate challenging and important transformations, there remains unexplored depth for creativity and future advancement. This Frontier highlights inter- and intramolecular combinations of transition metals and Lewis acids that together, provide a collaborative platform for chemical synthesis.

Unlocking metal-ligand cooperative catalytic photochemical benzene carbonylation: a mechanistic approach.

A key challenge in green synthesis is the catalytic transformation of renewable substrates at high atom and energy efficiency, with minimal energy input (ΔG ≈ 0). Non-thermal pathways, i.e., electrochemical and photochemical, can be used to leverage renewable energy resources to drive chemical processes at well-defined energy input and efficiency. Within this context, photochemical benzene carbonylation to produce benzaldehyde is a particularly interesting, albeit challenging, process that combines unfavorable thermodynamics (ΔG° = 1.7 kcal mol-1) and the breaking of strong C-H bonds (113.5 kcal mol-1) with full atom efficiency and the use of renewable starting materials. Herein, we present a mechanistic study of photochemical benzene carbonylation catalyzed by a rhodium-based pincer complex that is capable of metal-ligand cooperation. The catalytic cycle, comprising both thermal and non-thermal steps, was probed by NMR spectroscopy, UV-visible spectroscopy and spectrophotochemistry, and density functional theory calculations. This investigation provided us with a detailed understanding of the reaction mechanism, allowing us to unlock the catalytic reactivity of the Rh-pincer complex, which represents the first example of a metal-ligand cooperative system for benzene carbonylation, exhibiting excellent selectivity.

Ruthenium-Catalyzed Self-Coupling of Secondary Alcohols.

A simple catalytic method for self-coupling of secondary alcohols leading to the synthesis of β-branched ketones under mild conditions is reported. Well-defined ruthenium pincer complex catalyzed the reactions. Optimization studies revealed that sodium tert-butoxide is an appropriate base for this transformation. Functionalized aryl methanols, heteroaryl methanols, and linear and branched aliphatic secondary alcohols underwent facile catalytic self-coupling reactions. Mechanistic studies revealed that both catalyst and base are crucial to achieve dehydrogenation of secondary alcohols to ketones, their subsequent controlled aldol condensation, and further hydrogenation of α,β-unsaturated intermediates, leading to the selective formation of β-branched ketone products. Notably, the noninnocent PNP ligand which displays amine-amide metal-ligand cooperation operative in a catalyst played a key role in facilitating this catalytic self-coupling of secondary alcohols. Liberated molecular hydrogen and water are the only byproducts.