The iron porphyrin core in the active site of nature’s Cytochrome P450 monooxygenases catalyzes numerous highly selective oxygen insertions into C–H bonds with excellent reaction rates under mild physiological conditions. Inspired by these remarkable transformations, various metallo-porphyrin catalysts have been studied extensively for the direct C-H oxygenation of methylene compounds to their corresponding secondary alcohols. A major focus in this area has been the development of enantioselective oxygenation methods in which a transition metal catalyst (i.e. Ru, Fe, Mn) mediates the oxygenation of prochiral methylene compounds by a stoichiometric oxidant. However, site- and enantioselective C–H oxygenation remains challenging due to low conversions (&lt;40%) and moderate enantioselectivities (72-87% ee). A promising approach for achieving improved selectivity and reactivity is the development of a catalyst that facilitates a distinct binding mode for a given substrate and thus provides superior site- and enantioselectivity in the oxygenation protocol. Very recently, we have shown that a hydrogen bonding ligand serves as a key element in controlling the selectivity of a manganese porphyrin catalyzed C-H oxygenation reaction. 3,3-Disubstituted 3,4-dihydroquinolones reacted exclusively and with high enantioselectivity at position C4 of the heterocyclic skeleton (Figure 1). In our detailed kinetic and mechanistic studies (e.g. KIE studies), we have found evidence that the reaction likely occurs via an oxygen transfer from a manganese oxo complex by a rebound mechanism. Interestingly, it seems feasible to address distinct C-H positions in a given substrate by spatially adjusting the position of the catalytic entity relative to the hydrogen bonding substrate. Therefore, our current work focuses on the design of new catalysts, which could potentially allow for the differentiation between multiple reactive double bonds in epoxidation reactions catalyzed by metallo-porphyrins. The most recent results of our studies will be disclosed.

Site- and enantioselective C–H oxygenation catalyzed by a chiral manganese porphyrin complex with a remote binding site

256th National Meeting (2018)

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