Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0810, Japan.
Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan.
Org Lett. 2022 Sep 9;24(35):6407-6411. doi: 10.1021/acs.orglett.2c02434. Epub 2022 Aug 26.
A new method for constructing the bicyclo[3.2.1]octane skeleton was developed by the intramolecular alkylation of a nitrile-side-chain-containing cyclohexanone derivative. The cyclization precursors were prepared via the stereoselective bromination of the triisopropylsilyl enol ethers of 4-substituted cyclohexanones. Upon treatment with LiNEt, the bromonitriles underwent a stereoselective intramolecular S2 reaction to afford bicyclo[3.2.1]octane derivatives with a cyano group on the convex face. The total synthesis of 2-isocyanoallopupukeanane (6.5% yield) from methyl vinyl ketone was accomplished via a 17-step transformation.
开发了一种通过含腈侧链的环己酮衍生物的分子内烷基化反应来构建双环[3.2.1]辛烷骨架的新方法。通过对 4-取代环己酮的三异丙基硅基烯醇醚进行立体选择性溴化反应来制备环化前体。用 LiNEt 处理后，溴代腈经历立体选择性的 S2 分子内反应，得到凸面上带有氰基的双环[3.2.1]辛烷衍生物。通过 17 步转化，从甲基乙烯酮完成了 2-异氰基全尿烷（6.5%收率）的全合成。
