Total Synthesis of Atisane-Type Diterpenoids: Application of Diels–Alder Cycloadditions of Podocarpane-Type Unmasked <i>ortho-</i>Benzoquinones

Few examples of [4 + 2] cycloaddition with unmasked <i>ortho</i>-benzoquinones (UMOBs) as carbodiene have been reported in complex molecule synthesis. Herein we report that this cycloaddition with podocarpane-type UMOB was developed and applied to construct fully functionalized bicyclo[2.2.2]­octanes. Based on this methodology, divergent total syntheses of atisane-type diterpenoids, including (±)-crotobarin, crotogoudin, atisane-3β,16α-diol, and 16<i>S</i>,17-dihydroxy-atisan-3-one, were accomplished in 14, 14, 12, and 16 steps, respectively. Key elements in these total syntheses include: (1) FeCl₃-catalyzed cationic cascade cyclization to construct podocarpane-type skeleton; (2) Mn­(III)/Co­(II)-catalyzed radical hydroxylation of alkene with high regio-, diastereo-, and chemoselectivities; (3) and a ketal-deprotection/lactone-opening/deprotonation/lactonization cascade. Additionally, the synthetic utility of the fully functionalized bicyclo[2.2.2]­octane framework was further elucidated by applying ring distortion strategy to afford different skeleton-rearranged natural product-like compounds