N-Heterocyclic Carbene-Catalyzed Highly Enantioselective Macrolactonization to Access Planar-Chiral Macrocycles

Abstract

An N-heterocyclic carbene (NHC)-catalyzed atroposelective macrolactonization has been disclosed. This approach affords planar-chiral macrocycles in high yields with excellent enantioselectivities over a broad substrate scope. Controlled experiments suggest that the enantioselectivity might arise from the cation– n interaction between the acyl azolium and the electron-rich moiety in the substrate. This mechanism is supported by density functional theory calculations, which also suggest an important π–π interaction in stabilizing the transition state.

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