Catalytic Asymmetric Synthesis of the Pentacyclic Core of (+)-Citrinadin A

The synthesis of the pentacylic core of (+)-cit-rinadin A is described. Our strategy harnesses the power of palladium-catalyzed trimethylenemethane chemistry (Pd-TMM) to form the key spirooxindole motif in a catalytic, asymmetric fashion. Upon the conversion of this spirooxindole to a vinyl epoxide electrophile, the piperidine ring is directly added via a diastereoselective metalation followed by an S(N)2' addition. The final ring of the pentacyclic core is then formed through an intramolecular S(N)2 displacement of the resulting activated alcohol.

Automated summary

The synthesis of the pentacylic core of (+)-cit-rinadin A was described using palladium-catalyzed trimethylenemethane chemistry. The key spirooxindole motif was formed in a catalytic, asymmetric fashion, with subsequent addition of the piperidine ring and final ring formation through an intramolecular displacement reaction.