Enantioselective Synthesis of Axially Chiral Diaryl Ethers through Chiral Phosphoric Acid-Catalyzed Desymmetric Acylation with Azlactones
Jiawei Xu, Wei Lin, Hanliang Zheng, Xin Li
Abstract
C–O axially chiral diaryl ethers play important roles in natural products and bioactive molecules, but because of the low rotational barrier and strict steric hindrance requirements, the catalytic asymmetric construction of axially chiral diaryl ethers still remains a challenge. Herein, we devised a strategy employing achiral azlactone for the desymmetrization of prochiral diamines under the catalysis of chiral phosphoric acid. The targeted C–O axially chiral diaryl ethers were obtained in very good yields (up to 98%) and high enantioselectivities (up to >99.5:0.5 er). The synthetic utility was demonstrated through large-scale reaction and transformations of the products. Moreover, DFT calculations were conducted to probe the origins of enantioselectivity.