Enantioselective Synthesis of Nonfused Eight-Membered O‑Heterocycles by Sequential Catalysis

This work describes a chiral bifunctional squaramide/DBU
sequential
catalytic strategy for the enantioselective synthesis of nonfused
chiral eight-membered O-heterocycles through the asymmetric addition
of ynones to β,γ-unsaturated α-ketoesters followed
by the regio- and diastereoselective cyclization of the adduct intermediates.
Mechanistic experiments revealed that an isomerization process should
be involved in the ring formation step, and the origin of the high
regioselectivity and diastereoselectivity has also been elucidated
by the DFT calculations.