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

Graphic 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. Supplementary Information The online version contains supplementary material available at 10.1007/s00775-021-01849-9.


General Remarks
All chemicals were purchased commercially (Table S1) and used without further purification unless otherwise noted.

Oxygenation of C1a and C1b
Complex C1a was oxygenated to give [O1I] + (0.5 mM) according to the protocol described in the manuscript at -80 °C and analyzed via UV/Vis spectroscopy ( Figure S20). Figure S20: UV/Vis spectrum of the oxygenation of C1a in tetrahydrofuran (0.5 mM) at -80 °C after two hours.
The reddish-brown reaction solution revealed two absorption bands at 370 nm and 290 nm, which were stable at -80 °C for at least 6 h. The absorption bands represent a quantity of the formed bis(µ-oxido) complex of approximately 65%.
Oxygenation of bischelate complex C1b led to a similar UV/Vis spectrum of the reddish-brown species, except the intensity of the absorption bands is significantly lower revealing only 43% formation of the bis(µ-oxido) complex.

Oxygenation of C2a and C2b
Complex C2a was oxygenated to give [O1]Br 2 (0.5 mM) according to the protocol described in the manuscript at -100 °C and analyzed via UV/Vis spectroscopy ( Figure S21). Figure S21: UV/Vis spectrum of the oxygenation of C2a in tetrahydrofuran (0.5 mM) at -100 °C after 33 s.
After the addition of C2a complex solution, an immediate color change to green was observed, which is similar to [O1](PF 6 ) 2 . [1] Absorption bands at 399 nm and 270 nm, documenting 70% quantity of [O1]Br 2 , were formed immediately at -100 °C and decayed completely within a few minutes. Here, no full formation of the bis(µ-oxido) species could be observed due a faster decay rate compared to the formation rate.
Oxygenation of bischelate complex C2b led to a similar UV/Vis spectrum of the greenish species, except the intensity of the absorption bands is significantly lower revealing only 36% formation of the bis(µ-oxido) complex.

Oxygenation of C3a and C3b
Complex C3a was oxygenated to give [O1]Cl 2 (0.5 mM) according to the protocol described in the manuscript at -100 °C and analyzed via UV/Vis spectroscopy ( Figure S22). Figure S22: UV/Vis spectrum of the oxygenation of C3a in tetrahydrofuran (0.5 mM) at -100 °C after 45 s.
After the addition of C3a complex solution, an immediate color change to green was observed, which is similar to [O1](PF 6 ) 2 . [1] Absorption bands at 386 nm (21000 M -1 cm -1 ) and 270 nm (50000 M -1 cm -1 ) were formed immediately at -100 °C and decayed quickly afterwards within minutes.
Oxygenation of bischelate complex C3b led to a similar UV/Vis spectrum of the greenish species, except the intensity of the absorption bands is significantly lower revealing only 50% formation of the bis(µ-oxido) complex.

Cryo-UHR-ESI Mass Spectrometry of the Oxygenation Reactions
The respective bis(µ-oxido) species (0.5 mM) was synthesized according to the protocol described in the manuscript and analyzed via Cryo-UHR-ESI mass spectrometry.

Titration of [O1I] + with Ligand L1
Complex C1a was oxygenated to give [O1I] + (1.25 mM) according to the protocol described in the manuscript. Excess of O 2 was removed by three cycles of evacuation and purging with N 2 . A fivefold stock solution of L1 (15.5 mg, 2.5 µmol, 5.0 eq) in acetonitrile (0.5 mL) was prepared and one-fifth of it positioned in a Hamilton syringe. The titrant was added stepwise in 0.1 mL (1.0 eq) steps. The titration experiment was followed by UV/Vis spectroscopy ( Figure S32). After stabilization of the optical spectrum, the next aliquot of L1 was injected.  [O1I] + , rt + 1.0 eq L1 + 2.0 eq L1 + 3.0 eq L1

Titration of [O1I] + with Iodide Source Bu 4 NI
Complex C1a was oxygenated to give [O1I] + (0.5 mM) according to the protocol described in the manuscript. Excess of O 2 was removed by three cycles of evacuation and purging with N 2 . A tenfold stock solution of Bu 4 NI (18.5 mg, 50.0 µmol, 10.0 eq) in acetonitrile (1.0 mL) was prepared and onetenth of it positioned in a Hamilton syringe. The titrant was added stepwise in 0.1 mL (1.0 eq) steps. The titration experiment was followed by UV/Vis spectroscopy ( Figure S31). After stabilization of the optical spectrum, the next aliquot of Bu 4 NI was injected.  [O1I] + , rt + 1.0 eq Bu 4 NI + 2.0 eq Bu 4 NI + 3.0 eq Bu 4 NI

Titration of [O1I] + with Copper Source [Cu(MeCN) 4 ]PF 6
Complex C1a was oxygenated at -80 °C to give [O1I] + (0.5 mM) according to the protocol described in the manuscript. Excess of O 2 was removed by three cycles of evacuation and purging with N 2 . A tenfold stock solution of [Cu(MeCN) 4 ]PF 6 (18.6 mg, 50.0 µmol, 10.0 eq) in acetonitrile (1.0 mL) was prepared and one-tenth of it positioned in a Hamilton syringe. The titrant was added stepwise in 0.1 mL (1.0 eq) steps. The titration experiment was followed by UV/Vis spectroscopy ( Figure S32). After stabilization of the optical spectrum, the next aliquot of [Cu(MeCN) 4 ]PF 6 was injected.

Titration of [O1](PF 6 ) 2 with Bromide Source Bu 4 NBr
The titration experiment was conducted according to the protocol described in the manuscript at -100 °C using tetrabutylammonium bromide and followed by UV/Vis spectroscopy ( Figure S33).

Titration of [O1](PF 6 ) 2 with Chloride Source Bu 4 NCl
The titration experiment was conducted according to the protocol described in the manuscript using tetrabutylammonium chloride and followed by UV/Vis spectroscopy ( Figure S34).

Stability of [O1I](CuI 2 ) towards H 2 O
Complex C1a was oxygenated to give [O1I](CuI 2 ) (0.5 mM) according to the protocol described in the manuscript. Excess of O 2 was removed by three cycles of evacuation and purging with N 2 . Degassed H 2 O (0.1 mL, 1 vol%) was added and the experiment was followed by UV/Vis spectroscopy ( Figure S35). After stabilization of the optical spectrum, the next aliquot of degassed H 2 O (1.0 mL, 10 vol%) was injected.
The amount of solvent for the substrate solutions varied due to solubility limitations (Table S3).

Reaction of [O1I](CuI 2 ) with Phenols
All reactions were conducted according to the protocol described in the manuscript.

Reaction of [O1I](CuI 2 ) with Triethylamine
Complex C1a was oxygenated to give [O1I](CuI 2 ) (0.5 mM) according to the protocol described in the manuscript. After addition of triethylamine (0.07 mL) no immediate color change was observed. The reaction was followed by UV/Vis spectroscopy. The decrease of the absorption band at 370 nm was observed over time ( Figure S36). After 80 min the reaction solution discolored slightly to orange.