Mechanisms for Hydrogen-Atom Abstraction by Mononuclear Copper(III) Cores: Hydrogen-Atom Transfer or Concerted Proton-Coupled Electron Transfer?

In a possibly biomimetic fashion, formally copper(III)-oxygen complexes LCu(III)-OH (1) and LCu(III)-OOCm (2) (L2- = N,N'-bis(2,6-diisopropylphenyl)-2,6-pyridinedicarboxamide, Cm = α,α-dimethylbenzyl) have been shown to activate X-H bonds (X = C, O). Herein, we demonstrate similar X-H bond activation by a formally Cu(III) complex supported by the same dicarboxamido ligand, LCu(III)-O2CAr1 (3, Ar1 = meta-chlorophenyl), and we compare its reactivity to that of 1 and 2. Kinetic measurements revealed a second order reaction with distinct differences in the rates: 1 reacts the fastest in the presence of O-H or C-H based substrates, followed by 3, which is followed by (unreactive) 2. The difference in reactivity is attributed to both a varying oxidizing ability of the studied complexes and to a variation in X-H bond functionalization mechanisms, which in these cases are characterized as either a hydrogen-atom transfer (HAT) or a concerted proton-coupled electron transfer (cPCET). Select theoretical tools have been employed to distinguish these two cases, both of which generally focus on whether the electron (e-) and proton (H+) travel "together" as a true H atom, (HAT), or whether the H+ and e- are transferred in concert, but travel between different donor/acceptor centers (cPCET). In this work, we reveal that both mechanisms are active for X-H bond activation by 1-3, with interesting variations as a function of substrate and copper functionality.

Low Reorganization Energy for Electron Self-Exchange by a Formally Copper(III,II) Redox Couple.

The rate constant for electron self-exchange (k11) between LCuOH and [LCuOH]- (L = bis-2,6-(2,6-diisopropylphenyl)carboximidopyridine) was determined using the Marcus cross relation. This work involved measurement of the rate of the cross-reaction between [Bu4N][LCuOH] and [Fc][BAr4F] (Fc+ = ferrocenium; BAr4F = tetrakis[3,5-bis(trifluoromethyl)phenyl]borate)) by stopped-flow methods at -88 °C in CH2Cl2 and measurement of the equilibrium constant for the redox process by UV-vis titrations under the same conditions. A value of k11 = 3 × 104 M-1 s-1 (-88 °C) led to estimation of a value 9 × 106 M-1 s-1 at 25 °C, which is among the highest values known for copper redox couples. Further Marcus analysis enabled determination of a low reorganization energy, λ = 0.95 ± 0.17 eV, attributed to minimal structural variation between the redox partners. In addition, the reaction entropy (ΔS°) associated with the LCuOH/[LCuOH]- self-exchange was determined from the temperature dependence of the redox potentials, and found to be dependent upon ionic strength. Comparisons to other Cu redox systems and potential new applications for the formally CuIII,II system are discussed.

Kineticomechanistic Study of the Redox pH Cycling Processes Occurring on a Robust Water-Soluble Cyanido-Bridged Mixed-Valence {CoIII/FeII}2 Square.

A kineticomechanistic study of reversible electron-transfer processes undergone by the water-soluble, cyanido-bridged mixed-valence [{CoIII{(Me)2(µ-ET)cyclen}}2{(µ-NC)2FeII(CN)4}2]2- square has been carried out. The oxidation reaction consists of a two-step process with the participation of a solvent-assisted outer-sphere complex, as a result of the establishment of hydrogen bonds that involve the oxo groups of the oxidant (peroxodisulfate) and the terminal cyanido ligands of the tetrametallic square. The formally endergonic reduction reaction of the fully oxidized ([{CoIII{(Me)2(µ-ET)cyclen}}2{(µ-NC)2FeIII(CN)4}2]) core by water, producing hydrogen peroxide from water even at low pH values, is also a two-step process. Each one of these processes requires a set of two preequilibria involving the association of OH- and its subsequent deprotonation by a further OH- anion. The structure of the square compound in its fully protonated form has also been determined by X-ray diffraction and shows the existence of strong hydrogen-bonding interactions, in agreement with the rather high basicity of the terminal cyanido ligands. Likewise, density functional theory calculations on the tetrametallic complex showed zones with negative electrostatic potential around the FeII centers of the square that would account for the establishment of the hydrogen bonds found in the solid state. Spectroelectrochemistry experiments demonstrated the singular stability of the {CoIII/FeII}22- complex, as well as that of their partially, {Co2III/FeIIIFeII}-, and fully, {CoIII/FeIII}2, oxidized counterparts because no hysteresis was observed in these measurements.

Organo-Copper(II) Complexes as Products of Radical Atom Transfer.

Copper complexes bearing polyamine chelate ligands are among the most widely used and highly active catalysts for atom transfer radical polymerization (ATRP). Copper(I) complexes of these ligands (CuIL) react with an alkyl halide initiator (RX) in the atom transfer step to generate the higher oxidation state halido complex CuIILX and the radical R•. However, CuIL present in the reaction also has the potential to react with the liberated radicals to generate the organometallic species CuIILR (where R is formally a carbanion). The reversible association of radical and CuIL would facilitate the operation of an alternate, competitive controlled radical polymerization pathway known as organometallic-mediated radical polymerization (OMRP). Recently this possibility has been proposed to occur for a number of different copper catalysts under ATRP conditions, but unequivocal evidence of this organometallic adduct is lacking. Herein we provide direct observation of this species, including an optical spectrum for two of the most commonly used copper catalysts. Furthermore, using cyclic voltammetry coupled to simulations, we are able to determine each of the key thermodynamic and kinetic steps involved in both the atom transfer and radical transfer pathways to assess the impact of ligand, solvent, and initiator on these.

Elucidating the mechanism of the Ley-Griffith (TPAP) alcohol oxidation.

The Ley-Griffith reaction is utilized extensively in the selective oxidation of alcohols to aldehydes or ketones. The central catalyst is commercially available tetra-n-propylammonium perruthenate (TPAP, n-Pr4N[RuO4]) which is used in combination with the co-oxidant N-methylmorpholine N-oxide (NMO). Although this reaction has been employed for more than 30 years, the mechanism remains unknown. Herein we report a comprehensive study of the oxidation of diphenylmethanol using the Ley-Griffith reagents to show that the rate determining step involves a single alcohol molecule, which is oxidised by a single perruthenate anion; NMO does not appear in rate law. A key finding of this study is that when pure n-Pr4N[RuO4] is employed in anhydrous solvent, alcohol oxidation initially proceeds very slowly. After this induction period, water produced by alcohol oxidation leads to partial formation of insoluble RuO2, which dramatically accelerates catalysis via a heterogeneous process. This is particularly relevant in a synthetic context where catalyst degradation is usually problematic. In this case a small amount of n-Pr4N[RuO4] must decompose to RuO2 to facilitate catalysis.

A Kinetico-Mechanistic Study on CuII Deactivators Employed in Atom Transfer Radical Polymerization.

Copper complexes of tertiary amine ligands have emerged as the catalysts of choice in the extensively employed atom transfer radical polymerization (ATRP) protocol. The halide ligand substitution reactions of five-coordinate copper(II) complexes of tris[2-(dimethylamino)ethyl]amine (Me6tren), one of the most active ATRP catalysts, has been studied in a range of organic solvents using stopped-flow techniques. The kinetic and activation parameters indicate that substitution reactions on [CuII(Me6tren)X]+ (X- = Cl- and Br-) and [CuII(Me6tren)(Solv)]2+ (Solv = MeCN, DMF, DMSO, MeOH, EtOH) are dissociatively activated; this behavior is independent of the solvent used. Adjusting the effective concentration of the solvent by addition of an olefinic monomer to the solution does not affect the kinetics of the halide binding (kon) but can alter the outer-sphere association equilibrium constant (KOS) between reactants prior to the formal ligand substitution. Halide (X-/Y-) exchange reactions (X = Br and Y = Cl) involving the complex [Cu(Me6tren)X]+ and Y- reveal that the substitution is thermodynamically favored. The influence of solvent on the substitution reactions of [Cu(Me6tren)X]+ is complex; the more polar DMF confers a greater entropic driving force but larger enthalpic demands than MeCN. These substitution reactions are compared with those for copper(II) complexes bearing the tris[2-(diethylamino)ethyl]amine (Et6tren) and tris[2-(pyridyl)methyl]amine (tpa) ligands, which have also been used as catalysts for ATRP. Changing the ligand has a significant impact on the kinetics of X-/Y- exchange. These correlations are discussed in relation to the ability of five-coordinate [CuLX]+ complexes to deactivate radicals in ATRP.

N-Oxides rescue Ru(v) in catalytic Griffith-Ley (TPAP) alcohol oxidations.

The redox and ligand exchange reactions of oxido-ruthenium complexes are central to the function of the Sharpless and Griffith-Ley one-step alcohol oxidation protocols. However, their mechanisms have not been elucidated. Cyclic voltammetry and UV-vis spectroelectrochemical analysis of [RuO4](-) has provided new insight into the key ruthenium oxidation states involved in catalysis. Furthermore, the oxidation states sensitive to the presence of the N-oxide co-oxidant N-methylmorpholine N-oxide (NMO), and its role in catalysis, have been determined.

New method for exploring deactivation kinetics in copper-catalyzed atom-transfer-radical reactions.

Copper polyamine complexes are among the most utilized catalysts for controlled radical polymerization reactions. Copper(I) complexes may react reversibly with an alkyl halide to form an alkyl radical, which promotes polymerization, and a copper(II) halido complex in a step known as activation. The kinetics of the reverse reaction between the alkyl radical and higher oxidation-state copper complex (deactivation) are less studied because these reactions approach diffusion-controlled rates, and it is difficult to isolate or quantify the concentration of the alkyl radical (R(•)) in situ. Herein we report a broadly applicable electrochemical technique for simultaneously measuring the kinetics of deactivation and kinetics of activation.

Solvent dependent anion dissociation limits copper(I) catalysed atom transfer reactions.

Atom transfer radical addition (ATRA) and polymerisation (ATRP) reactions are commonly catalyzed by copper(I) complexes which react, reversibly, with a dormant alkyl halide initiator (RX) releasing a reactive organic radical R˙. The copper catalyst bears a multidentate N-donor ligand (L) and the active catalyst is simply Cu(I)L. The role of the catalyst in these reactions is to abstract a halogen atom from RX forming the corresponding higher oxidation state species Cu(II)LX. However, in order to perform its catalytic function (in multiple turnovers) the halido ligand must be released from the copper ion en route to regenerating the active catalyst Cu(I)L. In this work we investigate the kinetics of the Cu(I)LX/Cu(I)L equilibrium where L is the tridentate N,N,N',N'',N''-pentamethyl-diethylenetriamine (PMDETA). Using electrochemical analysis we find that the rate of formation of the active catalyst Cu(I)L is strongly dependent on solvent. We demonstrate that both the kinetics and thermodynamics of this simple ligand exchange reaction are critical in the overall reaction pathway.