Click. Coordinate. Catalyze. Using CuAAC Click Ligands in Small‐Molecule Model Chemistry of Tyrosinase

Abstract

Three triazolylmethylpyridine ligands are synthesized using the copper‐catalyzed azide‐alkyne cycloaddition (CuAAC). The corresponding copper(I) complexes are investigated as catalysts for the oxygenation of several monophenols, in analogy to the enzyme tyrosinase. Importantly, they show a higher catalytic activity than previously investigated systems. This is ascribed to the lower charge donation of the electron‐poor triazole heterocycle, supporting the hydroxylation of phenolic substrates by an electrophilic substitution mechanism.

Employing Linear Tridentate Ligands with Pyrazole End Groups in Catalytic Tyrosinase Model Chemistry: Does Hemilability Matter?

“…To conclude, both Cu I complexes of the pzma ligand 1a show a κ 2 bonding mode, similar to previously investigated Cu I complexes supported by bidentate ligands; i.e., the pyrazole N donors are bound to the Cu I ion whereas the tertiary amine does not coordinate. Unfortunately, we do not have structural information on a Cu I complex supported by 1b .…”

“…So far our group exclusively used bidentate ligands like, e.g., L py 1 , to emulate the reactivity of tyrosinase (Scheme ) . Variation of the N donor groups, their spatial separation and the type of counterions was found to alter the reactivity of derived copper(I) complexes regarding the mono‐oxygenation of monophenols . In contrast to an inactive system that only contains pyridines ( DPM ), introduction of one pyrazole donor ( PMP ) or two pyrazole donors ( BPM ) increases the catalytic activity significantly , …”

“…Ligands used for model systems capable of oxygenation (except D[PM] of several substrates in a tyrosinase‐like reaction , , …”

Copper‐Catalyzed Monooxygenation of Phenols: Evidence for a Mononuclear Reaction Mechanism

“…Within this project steric and electronic effects of primarily applied bidentate N-donor ligands were investigated in detail. [5,6,[20][21][22][23][24] Catalytic runs usually involve 50 equiv of monophenol along with 100 equiv of NEt 3 with respect to a mononuclear Cu I precursor (Bulkowski-Réglier conditions). [9,25] Nevertheless, conversion of the starting monophenol to the desired o-quinone was always found to be far from complete.…”

“…[9,25] Nevertheless, conversion of the starting monophenol to the desired o-quinone was always found to be far from complete. [5,6,20,23,24] In order to explain the low turnover numbers, we looked for possible decomposition pathways of the catalysts leading to dead-end species. In this context, the dinuclear Cu II complex [Cu 2 (μ-F)(dmPMP) 4 ]-(PF 6 ) 3 (dmPMP = 2-[(3,5-dimethyl-1H-pyrazol-1-yl)methyl]pyridine) was isolated from the pyrazole-based dmPMP system that exhibited a comparatively low (11 %) conversion of DTBP-H to DTBQ.…”