Rapid Access to Spirocyclic Oxindole Alkaloids: Application of the Asymmetric Palladium-Catalyzed [3 + 2] Trimethylenemethane Cycloaddition

The marcfortines are complex secondary metabolites that show potent anthelmintic activity and are characterized by the presence of a bicyclo[2.2.2]­diazaoctane fused to a spirooxindole. Herein, we report the synthesis of two members of this family. The synthesis of marcfortine B utilizes a carboxylative TMM cycloaddition to establish the spirocyclic core, followed by an intramolecular Michael addition and oxidative radical cyclization to access the strained bicyclic ring system. In addition, the first asymmetric synthesis of (−)-marcfortine C is described. The key step involves a cyano-substituted TMM cycloaddition, which proceeds in nearly quantitative yield with high diastereo- and enantioselectivity. The resulting chiral center was used to establish all remaining stereocenters in the natural product.

马科福汀类（marcfortines）是一类结构复杂的次级代谢产物，具有强效的驱虫活性，其结构特征为双环[2.2.2]二氮杂辛烷与螺吲哚酮稠合。本文报道了该家族中两个成员的全合成：马科福汀B的合成以羧化TMM环加成反应构建螺环核心，随后通过分子内迈克尔加成与氧化自由基环化，得到具有张力的双环骨架。此外，本文还首次实现了(−)-马科福汀C的不对称全合成，其关键步骤为氰基取代的TMM环加成反应，该反应以近乎定量的收率完成，同时展现出优异的非对映选择性与对映选择性。所得手性中心可用于构建天然产物中其余所有立体中心。