10.1021/ja101994q
The research details the total synthesis of (-)-anominine, a biologically active diterpenoid compound. The synthesis involves the use of several key chemicals and transformations. The process begins with an asymmetric Robinson annulation of dione 2 using N-Ts-(Sa)-binam-L-Pro as a catalyst to create quaternary stereogenic centers. The enantioenriched intermediate 3 is then used in a conjugated addition reaction to form compound 4. A Wittig methylenation and subsequent oxidation with IBX in the presence of TsOH lead to the formation of endocyclic enone 6. The lithium enolate of 6 reacts with Eschenmoser’s salt and undergoes m-CPBA oxidation to yield the exocyclic enone, which is reduced to obtain stereochemically pure 7. Further reductions and rearrangements, including a sigmatropic rearrangement in a wet medium, lead to the key intermediate 9. The synthesis continues with selective transformations, including hydroboration, hydrogenation, and acetylation, followed by allylic oxidation and Dess-Martin oxidation to form 12. The final steps involve coupling with zirconium tetrachloride, oxidation with Ley’s perruthenate, Wittig bishomologation, and olefin cross-metathesis to achieve the target compound (-)-anominine. The success of the synthesis relies on chemoselective transformations controlled by the structurally congested nature of the bicyclic core and the development of an efficient method for synthesizing Wieland-Miescher ketone compounds.
