Affiliation:
1. Beijing National Laboratory for Molecular Sciences CAS Key Laboratory of Molecular Recognition and Function CAS Research/Education Center for Excellence in Molecular Sciences Institute of Chemistry Chinese Academy of Sciences 100190 Beijing China
2. University of Chinese Academy of Sciences 100049 Beijing China
Abstract
AbstractAxially chiral diaryl ethers are present in numerous natural products and bioactive molecules. However, only few catalytic enantioselective approaches have been established to access diaryl ether atropisomers. Herein, we report the N‐heterocyclic carbene‐catalyzed enantioselective synthesis of axially chiral diaryl ethers via desymmetrization of prochiral 2‐aryloxyisophthalaldehydes with aliphatic alcohols, phenol derivatives, and heteroaromatic amines. This reaction features mild reaction conditions, good functional group tolerance, broad substrate scope and excellent enantioselectivity. The utility of this methodology is illustrated by late‐stage functionalization, gram‐scale synthesis, and diverse enantioretentive transformations. Control experiments and DFT calculations support the association of NHC‐catalyzed desymmetrization with following kinetic resolution to enhance the enantioselectivity.
Funder
National Natural Science Foundation of China