Generation and Aerobic Oxidative Catalysis of a Cu(II) Superoxo Complex Supported by a Redox-Active Ligand

Abstract

Cu systems feature prominently in aerobic oxidative catalysis in both biology and synthetic chemistry. Metal ligand cooperativity is a common theme in both areas as exemplified by galactose oxidase and by aminoxyl radicals in alcohol oxidations. This has motivated investigations into the aerobic chemistry of Cu and specifically the isolation and study of Cu-superoxo species that are invoked as key catalytic intermediates. While several examples of complexes that model biologically relevant Cu(II) superoxo intermediates have been reported, they are not typically competent aerobic catalysts. Here, we report a new Cu complex of the redox-active ligand ^tBu,TolDHP (2,5-bis((2-t-butylhydrazono)(p-tolyl)methyl)-pyrrole) that activates O₂ to generate a catalytically active Cu(II)-superoxo complex via ligand-based electron transfer. Characterization using ultraviolet (UV)-visible spectroscopy, Raman isotope labeling studies, and Cu extended X-ray absorption fine structure (EXAFS) analysis confirms the assignment of an end-on κ¹ superoxo complex. This Cu-O₂ complex engages in a range of aerobic catalytic oxidations with substrates including alcohols and aldehydes. These results demonstrate that bioinspired Cu systems can not only model important bioinorganic intermediates but can also mediate and provide mechanistic insight into aerobic oxidative transformations.

Figure 1.

Overview of representative (A) Cu(I) + aminoxyl catalysts for aerobic oxidations, (B) general model compound structures based on Cu monooxygenase and oxidase active sites, and this work: a bioinspired Cu(II) aerobic oxidation catalyst with a well-characterized Cu-superoxo intermediate.

Figure 2.

(A) SXRD of 1. Ellipsoids are set to 50% probability and hydrogen atoms have been omitted for clarity. Selected bond lengths and angles: Cu1–N1 1.895(3) Å, Cu1–N3 1.952(3) Å, Cu1–N5 1.890(3) Å, N1–N2 1.289(3) Å, N5–N4 1.293(4) Å, C9–C10 1.347(5) Å, N1–Cu1–N3 93.66(1)°, N5–Cu1–N3 93.83(1)°. (B) Cyclic voltammogram of 1 (black line) and [^tBu,TolDHP^•]Ni (gray line) in THF (1 mM [Cu] or [Ni], 0.1 M NBu4PF6, scan rate 100 mV s^–1). The small shoulder at −0.3 V for 1 arises from a small impurity in the electrolyte (Figure S29).

Figure 3.

(A) Cu K-edge X-ray absorption data for 1 (black) and 2 (green) with the smoothed first derivative of normalized absorbance (inset). Dashed line indicates the energy at half-maximum normalized absorbance. (B) Frontier natural orbitals and their natural occupation numbers (λ) for 1 along with fractional atomic orbital contributions to the natural orbitals for Cu (Cu_frac). Data obtained via [14,14] V2RDM CASSCF calculations with the 6–31G* basis set.

Figure 4.

(A) UV-visible spectroscopy of 0.015 mM 1 in DCM at 25 °C upon addition of 2 mL of O₂ where 1 is black and 3 is red. Formation of 3 with scans every 2 minutes starting 4 minutes after O₂ addition. Extinction coefficient is based on initial concentration of 1, assuming complete conversion to 3. (B) Variable isotope Raman spectra of the reaction of 1 with O₂ at room temperature to form 3. The reactions with ¹⁶O₂ vs. ¹⁸O₂ are shown in the superoxo stretching region. (C) Cu K-edge X-ray absorption data for 1 (black) and 3 (red) with an expanded pre-edge region (inset). (D) R-space EXAFS fitting for 3, with k-space shown in the inset (data, black; fits, red).

Figure 5.

DFT computed geometries and energies of hydrazine dehydrogenation by 3. Calculations were carried out with the M06L functional and a def2-TZVP basis set, with a def2-TZVPP basis set for Cu. Cu is shown in orange, C in gray, N in blue, O in red, and H in white. Only H-atoms involved in substrate dehydrogenation are shown.

Scheme 1.

Synthesis of 1, 2, and 3.

Scheme 2.

Catalytic oxidative reactivity of 3. All reactions were carried out with 10 mol% 1 under 1 atm O₂ for 18 h in DCM, with the exception of benzyl alcohol which was in THF to better tolerate tBuOK. Yield determined by ¹H NMR spectroscopy (³¹P NMR for PPh3) and is based on integration compared to an internal standard (mesitylene) or the ratio of product/(product + starting material) for PPh₃.

Scheme 3.

Mechanistic comparison of synthetic and biological Cu aerobic oxidative catalysts. The colored arrows and structures refer to mechanistic steps and intermediates for the [^{tBu, Tol}DHP]Cu (black), GO (red), and Cu/aminoxyl (blue) catalytic systems, with overlayed multi-color arrows and boxes notating steps or intermediates that are shared by the indicated systems. Note that the two rightmost steps for GO are intramolecular proton transfers mediated by an active site phenol/phenolate which is not shown.