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A Divergent Enantioselective Total Synthesis of Post-Iboga Indole Alkaloids
Jie Zhou1,2, Dong-Xing Tan1,3, Fu-She Han1,3,4
1CAS Key Lab of High-Performance Synthetic Rubber and its Composite Materials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Remin Street, Changchun, Jilin, 130022, China.
Abstract:
Divergent enantioselective total syntheses of five naturally occurring post-iboga indole alkaloids, dippinine B and C, 10,11-demethoxychippiine, 3-O-methyl-10,11-demethoxychippiine, and 3-hydroxy-3,4-secocoronaridine, as well as the two analogues 11-demethoxydippinine A and D, are presented for the first time. The enantioenriched aza[3.3.1]-bridged cycle, a common core intermediate to the target molecules, was constructed through an asymmetric phase-transfer-catalyzed Michael/aldol cascade reaction. The challenging azepane ring fused around the indole ring and the [3.3.1]-bridged cycle were installed through an intramolecular SN 2'-type reaction. These cyclization strategies enabled rapid construction of the [6.5.6.6.7]-pentacyclic core at an early stage. Highlights of the late-stage synthetic steps include a Pd-catalyzed Stille coupling and a highly stereoselective catalyst-controlled hydrogenation to incorporate the side chain at C20 with both R and S configurations in the natural products.
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