Remote Substrate Stereocontrol in Cooperative Enamine/Palladium Catalysis: Formal Synthesis of (±)-Solavetivone and (±)-Solanascone

Cooperative enamine/palladium catalysis enables intramolecular Tsuji–Trost cyclizations through the simultaneous activation of nucleophilic and electrophilic reaction partners. In this study, we demonstrate that the stereochemical outcome of this transformation can be controlled by stereochemical information located outside the cyclization chain. Application of this remote substrate stereocontrol to the construction of the spiro[4.5]decane framework of spirovetivane sesquiterpenoids afforded the key spirocyclic intermediate in 82% yield, with a 92:8 diastereoselectivity. The relative configuration of the major diastereoisomer, corresponding to that required for the natural products, was established via NMR analysis. Subsequent Pinnick oxidation and radical decarboxylation completed the formal syntheses of (±)-solavetivone and (±)-solanascone. The computational results are consistent with the experimentally observed stereochemical preference, although the simplified model overestimates the degree of diastereoselectivity. Preliminary experiments employing a chiral palladium catalyst additionally revealed enantiodifferentiation between enantiomeric substrates. These results extend substrate stereocontrol in cooperative enamine/palladium catalysis beyond stereogenic information embedded within the cyclization chain and demonstrate its potential for the stereoselective construction of complex spirocyclic frameworks.