Dioxygenase Reactivity of Nonheme Iron Hybrid Catalysts in Asymmetric cis-Dihydroxylation and Indole Oxidation Reactions by Dioxygen

Of particular interest in organic synthesis is the introduction of chirality into C=C bonds. In particular, the stereo- and regioselective oxidative functionalization of olefins has attracted considerable attention. This is one of the most challenging reactions in organic chemistry. Among vicinal cis-1,2-diols are important building blocks in the pharmaceutical and chemical industries. Optically active diols represent one of the most desirable molecules in the field of asymmetric synthesis because they can be easily transformed into various other functional groups.[1] Metal-based reagents for asymmetric cis-dihydroxylation of C=C double bonds are well established. Sharpless asymmetric cis-dihydroxylation[2] is still the method of choice for the formation of enantiopure cis-diols due to its efficiency, high functional group tolerance, and excellent stereoselectivities. However, alternative oxidants have been tested to circumvent the use of osmium, since the high cost, volatility, and toxicity of OsO4 prevent its successful application on an industrial scale. Two alternative systems that have been used for cis-dihydroxylation of olefins are permanganate (MnO4) both metal oxides hinders completion of the oxidation reaction at the diol stage, and overoxidation and formation of cleavage products are common side reactions. The increasing interest in the use of iron complexes for catalysis due to their abundance in nature, as well as their lack of toxicity, has also prompted the development and design of nonheme iron catalysts for olefin cis-dihydroxylation reactions.[5] Nevertheless, biomimetic nonheme iron complexes face challenges in cis-dihydroxylation due to iron-mediated H₂O₂ decomposition. This side reaction forms highly reactive hydroxyl radicals (•OH), causing ligand degradation, uncontrolled oxidation, and product decomposition. Moreover, the process demands an excessive substrate-to-H₂O₂ ratio for pursing the high catalytic efficiency, making it unsustainable for large-scale use. In this context, we propose a dual catalytic system that combines photocatalytic in situ production of H2O2 from H2O and O2 (2H2O + O2  2H2O2)[6,7] and selective cis-dihydroxylation with biomimetic iron catalysts by H₂O₂, which will provide a sustainable O₂-based green oxidation strategy for catalytic dioxygenation reactions.