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

Abstract

Comprehensive SummaryCedrane sesquiterpenes possess common tricyclo[5.3.1.01,5]undecane core structure. The varied oxa‐five‐membered ring decorating their core structure to form 8‐oxa‐tetracyclo[7.2.2.01,5.06,13]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[7.2.2.01,5.06,13]tridecane framework with five contiguous chiral centers in one step. In addition, a metal‐free I2‐catalyzed and DMSO‐mediated oxidative dehydroaromatization was applied to prepare curcuphenol and its derivatives from the highly functionalized cyclohexenones with minimal manipulations.