Selective Alkane Hydroxylation in a Fluorous Solvent System Catalyzed by a Fluorocarbon-Soluble Transition-Metal Catalyst.

Hydroxylation of aliphatic hydrocarbons requires highly reactive oxidants, but their strength can lead to undesired oxidation of the initially formed alcohols and solvents, undermining the product selectivity. To address these problems, we developed a novel catalytic system using fluorocarbon solvents. A cobalt complex supported by the fluorinated ligand, N,N,N',N',N″-pentakis-[CF3(CF2)7(CH2)3]-diethylenetriamine (Rf-deta), acts as an efficient catalyst [turnover number (TON) = 1203, turnover frequency = 51 ± 1 min-1] for cyclohexane hydroxylation with the m-chloroperbenzoic acid oxidant, achieving high alcohol selectivity (96%). Overoxidation to form cyclohexanone is minimized due to the separation of cyclohexanol from the reaction phase, comprising perfluoromethylcyclohexane and α,α,α-trifluorotoluene. The catalyst hydroxylates primary carbons (5 examples) and exhibits significant reactivity toward the terminal C-H bond of normal hexane (TON = 13). This system extends to the hydroxylation of the gaseous substrate butane, yielding the corresponding alcohols.

A rhodium(II)/rhodium(III) redox couple for C-H bond amination with alkylazides: a rhodium(III)-nitrenoid intermediate with a tetradentate [14]-macrocyclic ligand.

The catalytic activity of a rhodium(II) dimer complex, [RhII(TMAA)]2 (TMAA = tetramethyltetraaza[14]annulene), in C-H amination reactions with organic azides is explored. Organic azides (N3-R) with an electron-withdrawing group such as a sulfonyl group (trisylazide; R = S(O)2iPr3C6H2 (Trs)) and a simple alkyl group (R = (CH2)4Ph, (CH2)2OCH2Ph, CH2Ph, or C6H4NO2) are employed in intra- and intermolecular C-H bond amination reactions. The spectroscopic analysis using ESI-mass and EPR spectroscopy techniques on the reaction intermediate generated from [RhII(TMAA)]2 and N3-R reveals that a rhodium(III)-nitrenoid species is an active oxidant in the C-H bond amination reaction. DFT calculations suggest that the species can feature a radical localised nitrogen atom. The DFT calculation studies also indicate that the amination reaction involves hydrogen atom abstraction from the organic substrate R'-H by the NR moiety of 2N˙R and successive rebound of the generated organic radical intermediate R'˙ to [RhIII(NH-R)(TMAA)], giving [RhII(TMAA)] and R'-NH-R (amination product).

Asymmetric Michael addition catalysed by copper-amyloid complexes.

We developed self-assembled peptides containing a partial amyloid ß protein sequence and a metal-coordination site. The amyloid fibril-copper complexes exhibited excellent reactivity and moderate enantioselectivity in Michael addition reactions with 2-azachalcone and dimethylmalonate. The catalytic amyloids were characterized using various measurements to confirm their amyloid-like nanofibre structures.

Characterization and Reactivity Studies of Mononuclear Tetrahedral Copper(II)-Halide Complexes.

Structures, physicochemical properties, and reactivity of the whole series of copper(II)-halide complexes (1X; X = F, Cl, Br, and I) were examined using a TMG3tach tridentate supporting ligand consisting of cis,cis-1,3,5-triaminocyclohexane (tach) and N,N,N',N'-tetramethylguanidine (TMG). The tach ligand framework with the bulky and strongly electron-donating TMG substituents enforces the copper(II) complexes to take a tetrahedral geometry, as inferred from the electron paramagnetic resonance (EPR) spectra, exhibiting relatively large gz and small Az values. The electronic absorption spectra of 1X agreed with the simulation spectra obtained by time-dependent density functional theory (TD-DFT) calculations on a slightly distorted tetrahedral geometry. 1I and 1Br gradually decomposed to generate the corresponding copper(I) complex and halide radical X•, and in the case of 1Br, intramolecular hydroxylation of a methyl group of the TMG substituent took place under aerobic conditions, which may be caused by the reaction of the generated copper(I) complex and dioxygen (O2), generating a reactive oxygen species. 1X except 1I showed hydrogen atom abstraction (HAA) reactivity toward 1,4-cyclohexadiene (CHD), where 1F exhibited the highest reactivity with a second-order rate constant as 1.4 × 10-3 M-1 s-1 at 25 °C. Such an HAA reactivity can be attributed to the higher basicity of F- and/or large bond dissociation free energy of conjugate acid H-F as well as the unstable copper(II) electronic state in the tetrahedral geometry.

Dioxygen Activation and Mandelate Decarboxylation by Iron(II) Complexes of N4 Ligands: Evidence for Dioxygen-Derived Intermediates from Cobalt Analogues.

The isolation, characterization, and dioxygen reactivity of monomeric [(TPA)MII(mandelate)]+ (M = Fe, 1; Co, 3) and dimeric [(BPMEN)2MII2(µ-mandelate)2]2+ (M = Fe, 2; Co, 4) (TPA = tris(2-pyridylmethyl)amine and BPMEN = N1,N2-dimethyl-N1,N2-bis(pyridin-2-yl-methyl)ethane-1,2-diamine) complexes are reported. The iron(II)- and cobalt(II)-mandelate complexes react with dioxygen to afford benzaldehyde and benzoic acid in a 1:1 ratio. In the reactions, one oxygen atom from dioxygen is incorporated into benzoic acid, but benzaldehyde does not derive any oxygen atom from dioxygen. While no O2-derived intermediate is observed with the iron(II)-mandelate complexes, the analogous cobalt(II) complexes react with dioxygen at a low temperature (-80 °C) to generate the corresponding cobalt(III)-superoxo species (S), a key intermediate implicated in the initiation of mandelate decarboxylation. At -20 °C, the cobalt(II)-mandelate complexes bind dioxygen reversibly leading to the formation of µ-1,2-peroxo-dicobalt(III)-mandelate species (P). The geometric and electronic structures of the O2-derived intermediates (S and P) have been established by computational studies. The intermediates S and P upon treatment with a protic acid undergo decarboxylation to afford benzaldehyde (50%) with a concomitant formation of the corresponding µ-1,2-peroxo-µ-mandelate-dicobalt(III) (P1) species. The crystal structure of a peroxide species isolated from the cobalt(II)-carboxylate complex [(TPA)CoII(MPA)]+ (5) (MPA = 2-methoxyphenylacetate) supports the composition of P1. The observations of the dioxygen-derived intermediates from cobalt complexes and their electronic structure analyses not only provide information about the nature of active species involved in the decarboxylation of mandelate but also shed light on the mechanistic pathway of two-electron versus four-electron reduction of dioxygen.

C(sp3)-H bond activation by the carboxylate-adduct of osmium tetroxide (OsO4).

The reaction of osmium tetroxide (OsO4) and carboxylate anions (acetate: X- = AcO- and benzoate: X- = BzO-) gave 1 : 1 adducts, [OsO4(X)]- (1X), the structures of which were determined by X-ray crystallographic analysis. In both cases, the carboxylate anion X coordinates to the osmium centre to generate a distorted trigonal bipyramidal osmium(VIII) complex. The carboxylate adducts show a negative shift of the redox potentials (E1/2) and a red shift of the νOsO stretches as compared to those of tetrahedral OsO4 itself. Despite the negative shift of E1/2, the reactivity of these adduct complexes 1X was enhanced compared to that of OsO4 in benzylic C(sp3)-H bond oxidation. The reaction obeyed the first-order kinetics on both 1X and the substrates, giving the second-order rate constant (k2), which exhibits a linear correlation with the C-H bond dissociation energy (BDEC-H) of the substrates (xanthene, 9,10-dihydroanthracene, fluorene and 1,2,3,4-tetrahydronaphthalene) and a kinetic deuterium isotope effect (KIE) of 9.7 (k2(xanthene-h2)/k2(xanthene-d2)). On the basis of these kinetic data together with the DFT calculation results, we propose a stepwise reaction mechanism involving rate-limiting benzylic hydrogen atom abstraction and subsequent rebound of the generated organic radical intermediate to a remaining oxido group on the osmium centre.

Tin(II)-Nitrene Radical Complexes Formed by Electron Transfer from Redox-Active Ligand to Organic Azides and Their Reactivity in C(sp3)-H Activation.

A tin(II) complex coordinated by a sterically demanding o-phenylenediamido ligand is synthesized. The ligand is redox-active to reach a tin(II) complex with the diiminobenzosemiquinone radial anion in the oxidation by AgPF6. The tin(II) complex reacts with a series of nosylazides (x-NO2C6H4-SO2-N3; x = o, m, or p) at -30 °C to yield the corresponding nitrene radical bound tin(II) complexes. The nitrene radical complexes exhibit C(sp3)-H activation and amination reactivity.

Revisiting Alkane Hydroxylation with m-CPBA (m-Chloroperbenzoic Acid) Catalyzed by Nickel(II) Complexes.

Mechanistic studies are performed on the alkane hydroxylation with m-CPBA (m-chloroperbenzoic acid) catalyzed by nickel(II) complexes, NiII (L). In the oxidation of cycloalkanes, NiII (TPA) acts as an efficient catalyst with a high yield and a high alcohol selectivity. In the oxidation of adamantane, the tertiary carbon is predominantly oxidized. The reaction rate shows first-order dependence on [substrate] and [NiII (L)] but is independent on [m-CPBA]; vobs =k2 [substrate][NiII (L)]. The reaction exhibited a relatively large kinetic deuterium isotope effect (KIE) of 6.7, demonstrating that the hydrogen atom abstraction is involved in the rate-limiting step of the catalytic cycle. Furthermore, NiII (L) supported by related tetradentate ligands exhibit apparently different catalytic activity, suggesting contribution of the NiII (L) in the catalytic cycle. Based on the kinetic analysis and the significant effects of O2 and CCl4 on the product distribution pattern, possible contributions of (L)NiII -O. and the aroyloxyl radical as the reactive oxidants are discussed.

Controlling the Reactivity of Copper(II) Acylperoxide Complexes.

The redox state of the metallomonooxygenases is finely tuned by imposing specific coordination environments on the metal center to reduce the activation energy for the generation of active-oxygen species and subsequent substrate oxygenation reactions. In this study, copper(II) complexes supported by a series of linear tetradentate ligands consisting of a rigid 6-, 7-, or 8-membered cyclic diamine with two pyridylmethyl (-CH2Py) side arms (L6Pym2, L7Pym2, and L8Pym2) are employed to examine the effects of the coordination environment on the reactivity of their acylperoxide adduct complexes. The UV-vis and electron paramagnetic resonance spectroscopic data indicate that the ligand-field splitting between the dx2-y2 and dz2 orbitals of the starting copper(II) complexes increase with an increase of the ring size of the diamine moiety (L6Pym2 → L7Pym2 → L8Pym2). In the reaction of these copper(II) complexes with m-chloroperbenzoic acid (m-CPBA), the L6Pym2 complex gives a stable m-CPBA adduct complex, whereas the L7Pym2 and L8Pym2 complexes are immediately converted to the corresponding m-chlorobenzoic acid (m-CBA) adducts, indicating that the reactivity of the copper(II) acylperoxide complexes largely depends on the coordination environment induced by the supporting ligands. Density functional theory (DFT) calculations on the m-CPBA adduct complexes show that the ligand-field-splitting energy increases with an increase of the ring size of the diamine moiety, as in the case of the starting copper(II) complexes, which enhances the reactivity of the m-CPBA adduct complexes. The reasons for such different reactivities of the m-CPBA adduct complexes are evaluated by using DFT calculations.

Hydroxylation of Unactivated C(sp3)-H Bonds with m-Chloroperbenzoic Acid Catalyzed by an Iron(III) Complex Supported by a Trianionic Planar Tetradentate Ligand.

Hydroxylation of cyclohexane with m-chloroperbenzoic acid was examined in the presence of an iron(III) complex supported by a trianionic planar tetradentate ligand. The present reaction system shows a high turnover number of 2750 with a high product selectivity of alcohol (93%). The turnover frequency was 0.51 s-1, and the second-order rate constant (k) for the C-H bond activation of cyclohexane was 1.08 M-1 s-1, which is one of the highest values among the iron complexes in the oxidation of cyclohexane so far reported. The present catalytic system can be adapted to the hydroxylation of substrates having only primary C-H bonds such as 2,2,3,3-tetramethylbutane as well as gaseous alkanes such as butane, propane, and ethane. The involvement of an iron(III) acyl peroxido complex as the reactive species was suggested by spectroscopic measurements of the reaction solution.

Theoretical rationalization for the equilibrium between (µ-η2:η2-peroxido)CuIICuII and bis(µ-oxido)CuIIICuIII complexes: perturbational effects from ligand frameworks.

DFT calculations are carried out to investigate the geometric effects of the supporting ligands in the relative energies of the (µ-η2:η2-peroxido)CuIICuII complex 1 and the bis(µ-oxido)CuIIICuIII complex 2. The N3-tridentate ligand bearing acyclic propane diamine framework La preferentially provided 1, whereas the N3-tridentate ligand with cyclic diamine framework such as 1,4-diazacycloheptane Lb gave 2 after the oxygenation of the corresponding CuI complexes as reported previously [S. Itoh, et al., Inorg. Chem., 2014, 53, 8786-8794]. Calculations at the B3LYP*-D3 level of theory can reasonably explain the experimental results in relative energies, structures and harmonic frequencies of 1 and 2. Perturbational effects of the diamine chelates of La and Lb especially on the equilibrium of 1 and 2 are investigated in detail. In the range from 2.30 Å to 3.40 Å of the N-N distance in the diamine moiety, 1 is more stable than 2 by 8.4 kcal mol-1 at the distance of 3.40 Å. Calculated potential energies indicate that the decrease in the N-N distance is associated with a decrease in energy of 2, leading that 2 can be most stabilized at the N-N distance of 2.60 Å. Furthermore, molecular orbitals analyses are performed to explain that the energy gaps between the σ* orbital of the O-O bond and the dx2-y2 orbitals of the CuII ions of 1 get small as the diamine moiety is shrunk, leading to facilitate the O-O bond cleavage from 1 to 2.

Copper-Oxygen Dynamics in the Tyrosinase Mechanism.

The dinuclear copper enzyme, tyrosinase, activates O2 to form a (µ-η2 :η2 -peroxido)dicopper(II) species, which hydroxylates phenols to catechols. However, the exact mechanism of phenolase reaction in the catalytic site of tyrosinase is still under debate. We herein report the near atomic resolution X-ray crystal structures of the active tyrosinases with substrate l-tyrosine. At their catalytic sites, CuA moved toward l-tyrosine (CuA1 → CuA2), whose phenol oxygen directly coordinates to CuA2, involving the movement of CuB (CuB1 → CuB2). The crystal structures and spectroscopic analyses of the dioxygen-bound tyrosinases demonstrated that the peroxide ligand rotated, spontaneously weakening its O-O bond. Thus, the copper migration induced by the substrate-binding is accompanied by rearrangement of the bound peroxide species so as to provide one of the peroxide oxygen atoms with access to the phenol substrate's ϵ carbon atom.

Modelling a 'histidine brace' motif in mononuclear copper monooxygenases.

A mononuclear copper complex bearing a 'histidine brace' is synthesised and characterised as an active-site model of mononuclear copper monooxygenases such as lytic polysaccharide monooxygenases (LPMOs) and particulate methane monooxygenase (pMMO). The complex has similar structural and functional features to the active sites of the enzymes.

Cupin Variants as a Macromolecular Ligand Library for Stereoselective Michael Addition of Nitroalkanes.

Cupin superfamily proteins (TM1459) work as a macromolecular ligand framework with a double-stranded ß-barrel structure ligating to a Cu ion through histidine side chains. Variegating the first coordination sphere of TM1459 revealed that H52A and H54A/H58A mutants effectively catalyzed the diastereo- and enantioselective Michael addition reaction of nitroalkanes to an α,ß-unsaturated ketone. Moreover, calculated substrate docking signified C106N and F104W single-point mutations, which inverted the diastereoselectivity of H52A and further improved the stereoselectivity of H54A/H58A, respectively.

Characterization and Reactivity of a Tetrahedral Copper(II) Alkylperoxido Complex.

A tetrahedral CuII alkylperoxido complex [CuII (TMG3 tach)(OOCm)]+ (1OOCm ) (TMG3 tach={2,2',2''-[(1s,3s,5s)-cyclohexane-1,3,5-triyl]tris-(1,1,3,3-tetramethyl guanidine)}, OOCm=cumyl peroxide) is prepared and characterized by UV/Vis, cold-spray ionization mass spectroscopy (CSI-MS), resonance Raman, and EPR spectroscopic methods. Product analysis of the self-decomposition reaction of 1OOCm in acetonitrile (MeCN) indicates that the reaction involves O-O bond homolytic cleavage of the peroxide moiety with concomitant C-H bond activation of the solvent molecule. When an external substrate such as 1,4-cyclohexadiene (CHD) is added, the O-O bond homolysis leads to C-H activation of the substrate. Furthermore, the reaction of 1OOCm with 2,6-di-tert-butylphenol derivatives produces the corresponding phenoxyl radical species (ArO. ) together with a CuI complex through a concerted proton-electron transfer (CPET) mechanism. Details of the reaction mechanisms are explored by DFT calculations.

Direct Observation of Primary C-H Bond Oxidation by an Oxido-Iron(IV) Porphyrin π-Radical Cation Complex in a Fluorinated Carbon Solvent.

Oxido-iron(IV) porphyrin π-radical cation species are involved in a variety of heme-containing enzymes and have characteristic oxidation states consisting of a high-valent iron center and a π-conjugated macrocyclic ligand. However, the short lifetime of the complex has hampered detailed reactivity studies. Reported herein is a remarkable increase in the lifetime (80 s at 10 °C) of FeIV (TMP+. )(O)(Cl) (2; TMP=5,10,15,20-tetramesitylporphyrin dianion), produced by the oxidation of FeIII (TMP)(Cl) (1) by ozone in α,α,α-trifluorotoluene (TFT). The lifetime is 720 times longer compared to that of the currently most stable species reported to date. The increase in the lifetime improves the reaction efficiency of 2 toward inert alkane substrates, and allowed observation of the reaction of 2 with a primary C-H bond (BDEC-H =ca. 100 kcal mol-1 ) directly. Activation parameters for cyclohexane hydroxylation were also obtained.

Noninnocent Ligand in Rhodium(III)-Complex-Catalyzed C-H Bond Amination with Tosyl Azide.

Six-coordinate rhodium(III) complexes coordinated by a planar trianionic ligand (L3-) are synthesized. One of the axial positions is occupied by chloride (Cl-), bromide (Br-), or iodide (I-), and another axial position is coordinated by a solvent molecule such as acetonitrile (AN), water (H2O), tetrahydrofuran (THF), or pyridine (PY) to complete an octahedral rhodium(III) center; [RhIII(L3-)(X)(Y)]- (1X/Y; X = Cl-, Br-, or I-, Y = AN, H2O, THF, or PY). Coordination of the AN, H2O, and THF ligands to the metal center is rather weak, so that these solvent molecules are easily replaced by PY to give [RhIII(L3-)(Cl)(PY)]-. In the electrochemical measurements, all complexes have two reversible redox couples based on the ligand-centered oxidation L3- to L•2- and to L-, as reflected by the very similar redox potentials regardless of the different axial ligands. The rhodium(III) complexes catalyze C-H bond amination of xanthene with tosyl azide (TsN3). Because the yields of the aminated product are nearly the same among the complexes, replacement of the axial solvent ligands with TsN3 readily occurs to give a nitrene-radical-bound rhodium(III) complex, [RhIII(L•2-)(N•Ts)(X)]-, as an active oxidant, which is generated by one-electron transfer from the trianionic L3- to the nitrene nitrogen atom. Generation of such a diradical intermediate was substantiated by the direct reaction of 1Cl/AN with TsN3 in the absence of the substrate (xanthene). In this case, a rhodium(III) iminosemiquinone complex, 2, was generated by the intramolecular reaction between the nitrene-radical moiety and the radical moiety of the ligand L•2-.

A Bis(µ-oxido)dinickel(III) Complex with a Triplet Ground State.

A bis(µ-oxido)dinickel(III) complex was synthesized and characterized by single crystal X-ray diffraction, resonance Raman, and ESI-mass measurements. Magnetic susceptibility measurements by SQUID and EPR spectroscopy reveal that the complex has a triplet ground state, which is unprecedented for high-valent metal (M) complexes with [M2 (µ-O)2 ] diamond core. DFT studies indicate ferromagnetic coupling of the nickel(III) centers. The complex exhibits hydrogen abstraction reactivity and oxygenation reactivity toward external substrates.