Diastereoselective Formal [3+3] Cascade Cyclization towards Fused 4-Fluoroalkylated 3,4-Dihydro-2H-pyrans via Copper Catalysis

The cycloaddition and annulation reactions offer a powerful method toward various important substituted 3,4-dihydro-2H-pyran architectures. Nevertheless, the transformation for preparing fused-polycyclic ones still remains challenging yet highly desirable until now. Herein, we report a novel formal [3+3] cascade cyclization reaction to provide lactam-fused 4-fluoroalkylated 3,4-dihydropyran skeletons bearing three contiguous tertiary carbon centers via copper catalysis. Of note, these annulations proceeded in an exclusively diastereoselective manner through successive inert C(sp²)-Cl and C(sp³)-H functionalization, which exhibited highly site-selectivity and stereoselectivity. Additionally, evaluations on biological activities of the obtained products revealed that several products display inhibitory activity against Siha and H1975 cancer cell lines.