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

Abstract

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 pro-(S) C–H bond at the heterocyclic C-3 position is 1.9 kcal mol⁻¹ favored over the hydrogen atom abstraction of the pro-(R) C–H bond. This preferential reactivity results in the predominant formation of (S)-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.