Diastereoselective Formal [3+3] Cascade Cyclization towards Fused 4‐Fluoroalkylated 3,4‐Dihydro‐<scp>2<i>H</i></scp>‐pyrans via Copper Catalysis

Comprehensive Summary The cycloaddition and annulation reactions offer a powerful method toward various important substituted 3,4‐dihydro‐2 H ‐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(sp 2 )‐Cl and C(sp 3 )‐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.