Enantioselective synthesis of (-)-gilbertine via a cationic cascade cyclization
Enantioselective synthesis of (-)-gilbertine via a cationic cascade cyclization
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DOI：
10.1021/ja0399021
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发表时间：
2004-03-24
影响因子：
15
通讯作者：
Blechert, S
中科院分区：
文献类型：
--
作者：
Jiricek, J;Blechert, S
报道了（-）-gilbertine（2）的首次对映选择性合成，并测定了该天然产物的绝对构型。关键步骤采用阳离子级联反应，在一个步骤中形成四氢吡喃和哌啶环并构建五环框架。该合成策略利用柴崎反应来建立第一个立体中心。实现了3-取代的环己酮衍生物的缩合反应，仅得到所需的区域异构体。Japp-Klingemann Fischer吲哚方案成功地用作构建所需四氢咔唑（20）的收敛合成方法。此外，研究了该2，3-二取代的环己酮衍生物在差向异构化过程中的意外行为，导致对映异构体和外消旋体的不同化学行为。通过阳离子级联反应实现了非对映体的拆分，证明了该方法的通用性。值得注意的是，合成的17步序列易于执行，以5.5%的总产率得到（-）-吉尔伯特汀。
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 key step employs a cationic cascade reaction for a tetrahydropyrane and piperidine ring formation and the construction of the pentacyclic framework in one step. The synthetic strategy utilizes the Shibasaki reaction to build up the first stereogenic center. A formylation reaction of a 3-substituted cyclohexanone derivative was achieved, giving only the desired regioisomer. The Japp-Klingemann Fischer indole protocol was used successfully as a convergent synthetic approach for the construction of the desired tetrahydrocarbazole (20). Furthermore, an unexpected behaviour of this 2,3-disubstituted cyclohexanone derivative during an epimerization process was investigated, resulting in different chemical behaviour of the enantiomers and the racemate. The diastereomeric resolution was achieved via the cationic cascade reaction, demonstrating the versatility of this approach. Significantly, the synthetic 17-step sequence was easy to execute, giving (-)-gilbertine in 5.5% overall yield.