Asymmetric Organocatalytic (4 + 4) Annulation between 5-Alkenyl Thiazolones and α,β-Ynones: Access to Thiazole-Fused Eight-Membered Cyclic Ethers

Herein, we disclose an organocatalytic asymmetric (4 + 4) annulation reaction between 5-alkenyl thiazolones and α,β-ynones, leveraging 5-alkenyl thiazolones as 4π synthons in a (4 + 4) annulation for the first time. The one-pot approach catalyzed by a bifunctional thiourea catalyst delivers enantioenriched thiazole-fused eight-membered cyclic ethers with two contiguous tertiary stereocenters in excellent yields (up to 83%), demonstrating excellent control of regio-, chemo-, and stereoselectivities (up to 99% ee and >20:1 dr). Moreover, the reaction exhibits broad substrate generality, atom economy, and post-synthetic derivatization, further amplifying the synthetic utility of our developed methodology.