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.