Abstract

Phenols are abundant feedstock chemicals and their functionalization constitutes an attractive method for the synthesis of fine chemicals and materials. In biological systems, the copper-containing enzyme tyrosinase catalyzes the ortho-oxygenation of tyrosine into L-dopaquinone in the first step of the melanogenesis process. The copper centres in the enzyme activate O2 through the formation of μ-η2:η2-peroxodicopper(II) (SP) and subsequent electrophilic aromatic substitution on tyrosine provides L-dopaquinone. Despite many efforts for the past 50 years to develop a synthetic mimic for the aerobic oxygenation of phenols, a truly catalytic system for the selective ortho-oxygenation of phenols was only recently reported. The copper(I) complex of N,N’-di-tert-butylethylenediamine (DBED) is used as the precatalyst that activates oxygen and catalyzes the ortho-oxygenation of phenols. Investigating the mechanism of this catalytic process is the first objective of this research, whereby spectroscopic techniques are used to identify intermediates in this reaction and perform kinetic studies. The second objective of the research is the development of analogous phenol ortho-amination using nitrosoarenes as substitutes for oxygen.
The mechanistic studies were performed by spectroscopic characterization of intermediates and comparison with independently prepared complexes or literature spectra. In situ UV-vis spectroscopy of the reaction at 25 ºC demonstrated the formation of a copper(II)-semiquinone complex that persists during the oxygenation process. In order to identify the preceding intermediates, UV-vis spectroscopy at temperatures as low as -120 ºC was used, and the intermediates were characterized spectroscopically through comparison with similar reported species. Based on the observed intermediates a mechanism is proposed whereby the copper complex activates oxygen to forming SP; an oxygen atom is then transferred to a bound phenolate through electrophilic aromatic substitution. Kinetic studies using low-temperature stopped-flow techniques provides evidence for a binuclear mechanism of O2 activation and that the reaction rate is independent on phenol concentration. The mechanistic investigation suggests that oxygen activation and phenol functionalization proceed through the same pathway as the one observed with tyrosinase, thus substantiating the bio-mimetic nature of this catalytic reaction.
Nitrosoarenes (ArNO) are isoelectronic with singlet oxygen, therefore copper-ArNO complexes are structural and electronic mimics of copper-O2 complexes, and are expected to react in a similar way with external substrates. The redox lability of nitrosoarenes was proved by preparing and characterizing a copper(II)-nitrosoarene radical-anion complex. Structural and computational investigation confirmed its similarity to end-on copper(II)-superoxo species. Two-electron reduction of nitrosoarene was performed using the copper(I) complex of diamine ligand, and results in a complex that mimics the side-on copper(II)-peroxo (SP) structure. This complex undergoes stoichiometric reaction with phenolates to form aminophenols after reductive work-up, thus demonstrating similar reactivity to tyrosinase models.