Enantioselective Synthesis of C-O Axially Chiral Diaryl Ethers by NHC-Catalyzed Atroposelective Desymmetrization

Axially chiral diaryl ethers, a distinguished class of atropisomers possessing unique dual C-O axis, hold immense potential for diverse research domains. In contrast to the catalytic enantioselective synthesis of conventional single axis bearing atropisomers, the atroposelective synthesis of axially chiral ethers containing flexible C-O axis remains a significant challenge. Herein, we demonstrate the first N-heterocyclic carbene (NHC)-catalyzed synthesis of axially chiral diaryl ethers via atroposelective esterification of dialdehyde-containing diaryl ethers. Mechanistically, the reaction proceeds via NHC-catalyzed desymmetrization strategy to afford the corresponding axially chiral diaryl ether atropisomers in good yields and high enantioselectivities under mild conditions. The derivatization of the synthesized product expands the utility of present strategy via access to a library of C-O axially chiral compounds. The temperature dependency and preliminary investigations on the racemization barrier of C-O bonds are also presented. The atroposelective synthesis of C-O axially chiral diaryl ethers is demonstrated by the N-heterocyclic carbene (NHC)-catalyzed enantioselective esterification of dialdehyde containing diaryl ethers. The reaction proceeds via a desymmetrization of isophthalaldehyde derivatives bearing prochiral dual C-O axis affording atropoisomeric diaryl ethers with broad scope under mild conditions.**image

Automated summary

The N-heterocyclic carbene (NHC)-catalyzed enantioselective esterification of dialdehyde containing diaryl ethers demonstrates the atroposelective synthesis of C-O axially chiral diaryl ethers. The reaction proceeds via a desymmetrization strategy under mild conditions, yielding the corresponding axially chiral diaryl ether atropisomers with good yields and high enantioselectivities. The derivatization of the synthesized product expands the utility of the strategy and allows access to a library of C-O axially chiral compounds.