Room temperature stable multitalent: highly reactive and versatile copper guanidine complexes in oxygenation reactions

Abstract

Inspired by the efficiency of natural enzymes in organic transformation reactions, the development of synthetic catalysts for oxygenation and oxidation reactions under mild conditions still remains challenging. Tyrosinases serve as archetype when it comes to hydroxylation reactions involving molecular oxygen. We herein present new copper(I) guanidine halide complexes, capable of the activation of molecular oxygen at room temperature. The formation of the reactive bis(µ-oxido) dicopper(III) species and the influence of the anion are investigated by UV/Vis spectroscopy, mass spectrometry, and density functional theory. We highlight the catalytic hydroxylation activity towards diverse polycyclic aromatic alcohols under mild reaction conditions. The selective formation of reactive quinones provides a promising tool to design phenazine derivatives for medical applications.

Keywords: Copper catalysis; Dioxygen activation; Guanidine; Phenazine; Tyrosinase.

Fig. 1

Ligand design in synthetic model systems capable of tyrosinase-like oxygenation reactions [, –29]

Scheme 1

Synthesis of copper(I) hybrid guanidine complexes [Cu(L1)X] and [Cu(L1)₂]X (X = I, Br, Cl)

Fig. 2

Molecular structures of the complexes C1a-C3a in the solid state. Hydrogen atoms are omitted for clarity

Scheme 2

Oxygenation of monochelate complexes C1a-C3a

Fig. 3

UV/Vis spectra of the oxygenated C1a to give [O1I]⁺ (black) and the titration with CuI in tetrahydrofuran at room temperature

Fig. 4

Cryo-UHR-ESI mass spectrometry of [O1I]⁺ (left) and [O1](CuI₂)⁺ (right) in tetrahydrofuran at − 80 °C, which were observed in the oxygenation of C1a and C1a·CuI (red: experimental, black: calculated)

Fig. 5

Calculated structure of [O1I]⁺ (TPSSh/def2-TZVP, THF-PCM, GD3BJ)

Fig. 6

Molecular orbital and energy correlation of the [O1]²⁺ species (left) and of the [O1I]⁺ species (right). Main excitations are summarized (calculated by TD-DFT). The corresponding interactions of the MO and the influence of the iodide of the UV/vis spectra (middle) are presented

Fig. 7

UV/Vis spectra of the salt metathesis of [O1](PF₆)₂ (1.25 mM) with Bu₄NI in tetrahydrofuran at − 90 °C

Fig. 8

UV/Vis spectra of the formation of [O1I](CuI₂) (0.25 mM) in tetrahydrofuran at − 90 °C (Inset: expansion of the formation of [O1I](CuI₂))