Catalytic Asymmetric Conjugate Addition/Hydroalkoxylation Sequence: Expeditious Access to Enantioenriched Eight-Membered Cyclic Ether Derivatives

A sequential enantioselective conjugate addition/hydroalkoxylation between in situ generated ortho-quinomethanes and ynones by combining bifunctional squaramide and DBU catalysis has been developed. A variety of eight-membered cyclic ethers with two contiguous tertiary stereocenters were obtained in high yields with excellent stereoselectivities. This reaction not only provides a new strategy for constructing enantioenriched eight-membered cyclic ethers but also demonstrates the practicability of ynones as C4-syntons for the synthesis of chiral medium-membered rings.

Automated summary

A new method has been developed for the selective construction of enantioenriched eight-membered cyclic ethers by combining squaramide and DBU catalysis. The reaction yields a variety of eight-membered cyclic ethers with high stereoselectivity, showcasing the practicality of ynones as C4-syntons for synthesizing chiral medium-membered rings.