A mechanistic study of chiral manganese porphyrin-catalyzed enantioselective C–H hydroxylation reaction

We employed density functional theory (DFT) calculations to elucidate the mechanism and origin of enantioselectivity in the C-H hydroxylation reaction catalyzed by a chiral manganese porphyrin complex. Our study reveals that the chiral manganese porphyrin forms a two-point hydrogen bonding interaction with the substrate. Specifically, the hydrogen atom abstraction of the methylene <i>pro</i>-(<i>S</i>) C-H bond at the heterocyclic C-3 position is 1.9 kcal mol^-1 favored over the hydrogen atom abstraction of the <i>pro</i>-(<i>R</i>) C-H bond. This preferential reactivity results in the predominant formation of (<i>S</i>)-hydroxylated products. Our DFT calculations are consistent with the experimental findings of high enantioselectivity in the chiral manganese porphyrin catalyzed C(sp³)-H hydroxylation of lactam derivatives. The observed enantioselectivity arises from the formation of two-point hydrogen bonding between lactam derivatives and manganese porphyrin catalysts. Moreover, our computations indicate varying degrees of substrate distortion upon attack by high-valent manganese oxygen complexes at different hydrogen atoms.