Bio-inspired Manganese-catalyzed Aromatic C–H Hydroxylation leads to an Intramolecular C(sp2)–C(sp2) Coupling Reaction: A Product Inhibition Study in Aromatic Hydroxylation

The C–H hydroxylation of aromatic substrates with hydrogen peroxide to form phenol products catalyzed by bio-inspired manganese complexes 1a and 1b in fluorinated solvents has been recently studied in our group. The incorporation of bulky TIPS groups into the amino-pyridine ligand was found to favor aromatic C–H hydroxylation and overall catalytic efficiency for 1b over 1a. It was proposed that non-bulky complex 1a suffers from product inhibition due to phenolate binding to the manganese center, while this effect is less prominent for bulky complex 1b. In this work, we have investigated the origin of product inhibition and explained the lower activity of 1a using various spectroscopies, including UV-Vis and highresolution MS (HRMS). HRMS analysis showed the formation of manganese phenolate complexes and other manganese complexes during catalysis for the non-bulky as well as bulky complexes. HRMS also revealed the formation of a manganese-(2,2’-bi(parapropylphenolate)) species in which manganese has a high-valent +4 oxidation state. Catalytic experiments using independently synthesized manganese(II)-(bis(phenolate)) complexes 2c and 2d, demonstrated that these are catalytically active, whereas manganese(II)(2,2’biphenolate) complex 2e is not. Additionally, its VisPD spectrum points out that the high-valent [manganese(IV)(tipsbpmcn)(2,2’-bi(para-propylphenolate))]2+ species is responsible for the deep greenish-purple observed during catalysis. Overall, this work presents new insights into the mechanism of product inhibition in aromatic hydroxylation by bio-inspired manganese complexes through an ortho-ortho coupling pathway, which will aid further catalyst development.