Carbene-Catalyzed Atroposelective Construction of Chiral Diaryl Ethers

Atropoisomeric chemotypes of diaryl ethers related scaffolds are prevalent in naturally active compounds. Nevertheless, there remains considerable research to be carried out on the catalytic asymmetric synthesis of these axially chiral molecules. In this instance, we disclose the first N-heterocyclic carbene catalyzed synthesis of axially chiral diaryl ethers via atroposelective esterification of dialdehyde-containing diaryl ethers. The reaction proceeds mathematically through a desymmetrization method catalyzed by NHC, which results in the production of axially chiral diaryl ether atropisomers with good yields and high enantioselectivities in mild conditions. The chiral diaryl ether compounds can be utilized as precursors for further transformation into highly functionalized diaryl ethers with potential bioactivity and as chiral ligands with uses in asymmetric catalysis.