Carbene-Catalyzed Atroposelective Construction of Chiral Diaryl Ethers

Abstract

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.

Evolution in the asymmetric synthesis of biaryl ethers and related atropisomers

“…Using C-3 as NHC-pre-catalyst and Cs 2 CO 3 as a base assisted the abovedescribed desymmetrization of isopthaladehyde derivatives 24 with a broad range of alcohols (Scheme 8). 27 Again, an excellent level of enantioselectivity of esters 28 or alcohols 32 (formed by reduction of 28) was observed. With the triazolium salt C-6 as an NHC precursor, desymmetrization of isopthaladehyde derivatives 24 with a wide variety of aliphatic alcohols and some phenol derivatives yielded the desired biaryl ethers in good to excellent enantioselectivities (Scheme 9).…”