Enantioselective Synthesis of (-)-Gilbertine via a Cationic Cascade Cyclization

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• 作者：Jan Jiricek and Siegfried Blechert
• 刊名：Journal of the American Chemical Society
• 出版年：2004
• 出版时间：March 24, 2004
• 年：2004
• 卷：126
• 期：11
• 页码：3534 - 3538
• 全文大小：95K
• 年卷期：v.126,no.11(March 24, 2004)
• ISSN：1520-5126

文摘

Described is the first enantioselective synthesis of (-)-gilbertine (2), a member of the uleine-type family, and the determination of the absolute configuration of this natural product is reported. The keystep employs a cationic cascade reaction for a tetrahydropyrane and piperidine ring formation and theconstruction of the pentacyclic framework in one step. The synthetic strategy utilizes the Shibasaki reactionto build up the first stereogenic center. A formylation reaction of a 3-substituted cyclohexanone derivativewas achieved, giving only the desired regioisomer. The Japp-Klingemann Fischer indole protocol wasused successfully as a convergent synthetic approach for the construction of the desired tetrahydrocarbazole(20). Furthermore, an unexpected behavior of this 2,3-disubstituted cyclohexanone derivative during anepimerization process was investigated, resulting in different chemical behavior of the enantiomers andthe racemate. The diastereomeric resolution was achieved via the cationic cascade reaction, demonstratingthe versatility of this approach. Significantly, the synthetic 17-step sequence was easy to execute, giving(-)-gilbertine in 5.5% overall yield.