T. Daniel P. Stack

Phenolate Hydroxylation in a Bis(μ-oxo)dicopper(III) Complex : Lessons from the Guanidine/Amine Series

A new hybrid permethylated-amine-guanidine ligand based on a 1,3-propanediamine backbone (2L) and its Cu-O2 chemistry is reported. [(2L)CuI(MeCN)]1+ complex readily oxygenates at low temperatures in polar aprotic solvents to form a bis(mu-oxo)dicopper(III) (O) species (2b), similar to the parent bis-guanidine ligand complex (1b) and permethylated-diamine ligand complex (3b). UV-vis and X-ray absorption spectroscopy experiments confirm this assignment of 2b as an O species, and full formation of the 2:1 Cu-O2 complex is demonstrated by an optical titration with ferrocene-monocarboxylic acid (FcCOOH). The UV-vis spectra of 1b and 2b with guanidine ligation show low-intensity visible features assigned as guanidine pi --> Cu2O2 core transitions by time-dependent density functional theory (TD-DFT) calculations. Comparison of the reactivity among the three related complexes (1b-3b) with phenolate at 195 K is particularly insightful as only 2b hydroxylates 2,4-di-tert-butylphenolate to yield 3,5-di-tert-butylcatecholate (>95% yield) with the oxygen atom derived from O2, reminiscent of tyrosinase reactivity. 1b is unreactive, while 3b yields the C-C radical-coupled bis-phenol product. Attenuated outer-sphere oxidative strength of the O complexes and increased phenolate accessibility to the Cu2O2 core are attributes that correlate with phenolate hydroxylation reactivity observed in 2b. The comparative low-temperature reactivity of 1b-3b with FcCOOH (O-H BDE 71 kcal mol(-1)) to form the two-electron, two-proton reduced bis(mu-hydroxo)dicopper(II,II) complex is quantitative and presumably precedes through two sequential proton-coupled electron transfer (PCET) steps. Optical titrations along with DFT calculations support that the reduced complexes formed in the first step are more powerful oxidants than the parent O complexes. These mechanistic insights aid in understanding the phenol to bis-phenol reactivity exhibited by 2b and 3b.

Facile C−H Bond Cleavage via a Proton-Coupled Electron Transfer Involving a C−H···CuII Interaction

The present study provides mechanistic details of a mild aromatic C-H activation effected by a copper(II) center ligated in a triazamacrocylic ligand, affording equimolar amounts of a Cu(III)-aryl species and Cu(I) species as reaction products. At low temperatures the Cu(II) complex 1 forms a three-center, three-electron C-H...Cu(II) interaction, identified by pulse electron paramagnetic resonance spectroscopy and supported by density functional theory calculations. C-H bond cleavage is coupled with copper oxidation, as a Cu(III)-aryl product 2 is formed. This reaction proceeds to completion at 273 K within minutes through either a copper disproportionation reaction or, alternatively, even faster with 1 equiv of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), quantitatively yielding 2. Kinetic studies of both reactions strongly implicate a rate-limiting proton-coupled electron transfer as the key C-H activation step, a mechanism that does not conform to the C-H activation mechanism in a Ni(II) analogue or to any previously proposed C-H activation mechanisms.

Biomimetic modeling of copper oxidase reactivity.

Bioinspired copper-model-complexes that react with O(2) provide an opportunity to probe biological reactivity at a small-molecule level of detail. Biological structural information combined with appropriate ligand design has proven sufficient to create Cu:O(2) complexes capable of external substrate oxidation. Most notable developments during the review period are the bioinspired catalysts capable of aerobic alcohol-oxidation. The extension of this oxidative reactivity to other important organic transformations beyond the scope of the inspiring system completes a modeling paradigm.

Controlled loadings in a mesoporous material: click-on silica.

Hybrid mesoporous SBA-15 silicas were synthesized directly with variable alkylazide loading representing 2-50% surface coverage. These hybrid silica materials retain the favorable physical attributes of the parent SBA-15 materials and allow efficient covalent attachment of ethynylated organic moieties through a copper catalyzed 3 + 2 Huisgen cycloaddition reaction. Three distinctly different examples are provided demonstrating the efficiency and robust nature of this attachment synthetic strategy. The direct syntheses provide predefined loadings of randomly distributed organics within the materials, from site-dense to site-isolated. Such control over loadings along with simply implemented analytic procedures should facilitate the translation of homogeneous chemistries to heterogeneous supports.

Ligand Self-Recognition in the Self-Assembly of a [{Cu(L)}2]2+ Complex: The Role of Chirality

The chirality alone of a conformationally restricted, bifunctional ligand (L) is the basis for the self-recognition process schematically represented below. A racemic mixture of these ligands reacts with Cu+ ions quantitatively to generate a racemic mixture of a [(CuL)2 ]2+ homochiral complex (represented by cubes), where each complex contains ligands with identical configurations.

Electrocatalytic O2 Reduction by Covalently Immobilized Mononuclear Copper(I) Complexes: Evidence for a Binuclear Cu2O2 Intermediate

A Cu(I) complex of 3-ethynyl-phenanthroline covalently immobilized onto an azide-modified glassy carbon surface is an active electrocatalyst for the four-electron (4-e) reduction of O(2) to H(2)O. The rate of O(2) reduction is second-order in Cu coverage at moderate overpotential, suggesting that two Cu(I) species are necessary for efficient 4-e reduction of O(2). Mechanisms for O(2) reduction are proposed that are consistent with the observations for this covalently immobilized system and previously reported results for a similar physisorbed Cu(I) system.

Stereospecificity and Self‐Selectivity in the Generation of a Chiral Molecular Tetrahedron by Metal‐Assisted Self‐Assembly

The chiral bidentate ligand (S,S)-1 reacts stereospecifically with Ga3+ to generate a [Ga4 (L)6 ]12- molecular tetrahedron although similar ligands generate [Ga2 (L)3 ]6- complexes. The assembly of this complex is self-selective as a racemic mixture of the ligand sorts by chirality to generate an enantiomeric pair of homochiral complexes.

Catalytic phenol hydroxylation with dioxygen: extension of the tyrosinase mechanism beyond the protein matrix.

A pinnacle of bio-inorganic chemistry is the ability to leverage insights gleaned from metalloenzymes toward the design of small analogs capable of effecting catalytic reactivity outside the context of the natural system.[1,2] Structural mimicry of active sites is an attempt to insert a synthetic catalyst into an enzymatic mechanism. Such a mechanism evolves by selection pressures for efficiency and traverses an energetic path with barriers and wells neither too high nor too deep in energy – a critical factor of catalytic turnover.[3] An advantage of metalloenzymes over small metal complexes is the site-isolation of the metal center in the protein matrix with its attendant ability to attenuate destructive decay processes – reaction sinks. This protection provides access to thermal regimes that allows barriers and wells to be traversed. Synthetic complexes too must avoid any deleterious reactions, often necessitating deliberate incorporation of protective superstructures.[4,5] Such limitations make reproducing enzymatic catalytic reactivity in a synthetic complex with native substrates a significant challenge, as evidenced by the dearth of good examples, despite decades of effort.

Covalent heterogenization of a discrete Mn(II) bis-phen complex by a metal-template/metal-exchange method: an epoxidation catalyst with enhanced reactivity.

Considerable attention has been devoted to the immobilization of discrete epoxidation catalysts onto solid supports due to the possible benefits of site isolation such as increased catalyst stability, catalyst recycling, and product separation. A synthetic metal-template/metal-exchange method to imprint a covalently attached bis-1,10-phenanthroline coordination environment onto high-surface area, mesoporous SBA-15 silica is reported herein along with the epoxidation reactivity once reloaded with manganese. Comparisons of this imprinted material with material synthesized by random grafting of the ligand show that the template method creates more reproducible, solution-like bis-1,10-phenanthroline coordination at a variety of ligand loadings. Olefin epoxidation with peracetic acid shows the imprinted manganese catalysts have improved product selectivity for epoxides, greater substrate scope, more efficient use of oxidant, and higher reactivity than their homogeneous or grafted analogues independent of ligand loading. The randomly grafted manganese catalysts, however, show reactivity that varies with ligand loading while the homogeneous analogue degrades trisubstituted olefins and produces trans-epoxide products from cis-olefins. Efficient recycling behavior of the templated catalysts is also possible.

Self-assembly of the oxy-tyrosinase core and the fundamental components of phenolic hydroxylation

The enzyme tyrosinase contains two Cu(I) centres, trigonally coordinated by imidazole nitrogens of six conserved histidine residues. The enzyme activates O(2) to form a µ-η(2):η(2)-peroxo-dicopper(II) core, which hydroxylates tyrosine to a catechol in the first committed step of melanin biosynthesis. Here, we report a family of synthetic peroxo complexes, with spectroscopic and chemical features consistent with those of oxygenated tyrosinase, formed through the self-assembly of monodentate imidazole ligands, Cu(I) and O(2) at -125 °C. An extensively studied complex reproduces the enzymatic electrophilic oxidation of exogenous phenolic substrates to catechols in good stoichiometric yields. The self-assembly and subsequent reactivity support the intrinsic stability of the Cu(2)O(2) core with imidazole ligation, in the absence of a polypeptide framework, and the innate capacity to effect hydroxylation of phenolic substrates. These observations suggest that a foundational role of the protein matrix is to facilitate expression of properties native to the core by bearing the entropic costs of assembly and precluding undesired oxidative degradation pathways.