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
the various products that can be generated, the 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
?)[3] and ruthenium tetroxide
(RuO4).[4] However, the high oxidative potential of 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
H?O? 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-H?O? 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 H?O?, which will
provide a sustainable O?-based green oxidation strategy for catalytic dioxygenation
reactions.