Highly Stereocontrolled Total Syntheses of Cedrane Sesquiterpenes via Cascade [5+2] Cycloaddition/Etherification

Comprehensive Summary Cedrane sesquiterpenes possess common tricyclo[5.3.1.0(1,5)]undecane core structure. The varied oxa-five-membered ring decorating their core structure to form 8-oxa-tetracyclo[7.2.2.0(1,5).0(6,13)]tridecane framework, containing six consecutive chiral centers (including two all-carbon quaternary centers and one oxygenated quaternary carbon center), has proven to be a synthetic challenge and a biosynthetic mystery to date. Herein, we reported a distinct and biomimetic strategy to these sesquiterpenes resulting in the concise asymmetric total syntheses of three cedrane sesquiterpenes from simple commercially available building blocks. Key feature is exploitation of a cascade oxidative dearomatization-induced [5+2] cycloaddition/etherification to highly stereocontrolled construct 8-oxa-tetracyclo[7.2.2.0(1,5).0(6,13)]tridecane framework with five contiguous chiral centers in one step. In addition, a metal-free I-2-catalyzed and DMSO-mediated oxidative dehydroaromatization was applied to prepare curcuphenol and its derivatives from the highly functionalized cyclohexenones with minimal manipulations.