Enantioselective\nSynthesis of Nonfused Eight-Membered\nO‑Heterocycles by Sequential Catalysis

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