The Suzuki coupling reaction in the stereocontrolled synthesis of 9-cis-retinoic acid and its ring-demethylated analogues.
The Suzuki coupling reaction in the stereocontrolled synthesis of 9-cis-retinoic acid and its ring-demethylated analogues.
复制标题
9-顺式视黄酸及其环去甲基化类似物立体控制合成中的 Suzuki 偶联反应。
DOI：
10.1002/chin.200222211
复制
发表时间：
2001
期刊：
影响因子：
--
通讯作者：
A. D. de Lera
中科院分区：
文献类型：
--
作者：
Y. Pazos;B. Iglesias;A. D. de Lera
四烯基碘19与环己烯基硼酸酯18在铊的催化下发生Suzuki偶联反应，高产率地得到9-顺式维甲酸乙酯（12）。Suzuki反应的两种偶联配偶体在由它们的前体四烯基锡烷10和环己烯基碘13产生后立即反应更好。通过立体选择性Horner-Wadsworth-Emmons反应合成了几何均相的四烯基锡烷10，它由9-顺式维甲酸乙酯及其环脱甲基类似物的多烯侧链组成。另一方面，容易获得的环己酮是制备环修饰的9-顺式-视黄酸类似物所需的环己烯基硼酸酯的理想起始原料。对于受阻环己酮，腙转化为环己烯基碘。碘-锂交换和与B（OMe）（3）的捕获然后得到环己烯基硼酸酯。如果前体环己酮具有仲碳，则通过消除在用n-BuLi（Shapiro反应）处理三糖基腙时获得的C，N-二硫代硫酸化中间体来方便地形成烯基锂物质。上述方法都不允许从2-甲基环己酮生成更多取代的有机锂。然而，34和10的另一种Stille交叉偶联得到9-顺式-1，1-双去甲基视黄酸7。Suzuki和Stille偶联反应均在温和条件下进行，因此确保了类维生素A侧链几何形状的保留。
The thallium-accelerated Suzuki coupling reaction of tetraenyl iodide 19 and cyclohexenyl boronate 18 afforded ethyl 9-cis-retinoate (12) in high yield. Both coupling partners of the Suzuki reaction are better reacted immediately after generation from their precursors, tetraenylstannane 10 and cyclohexenyl iodide 13. The geometrically homogeneous tetraenylstannane 10, comprising the polyenic side chain of ethyl 9-cis-retinoate and its ring-demethylated analogues, was synthesized by a stereoselective Horner-Wadsworth-Emmons reaction. On the other hand, easily available cyclohexanones are ideal starting materials for preparation of the cyclohexenyl boronates required for the synthesis of the ring-modified 9-cis-retinoic acid analogues. For hindered cyclohexanones, hydrazones were converted to cyclohexenyl iodides. Iodine-lithium exchange and trapping with B(OMe)(3) then afforded the cyclohexenyl boronates. If the precursor cyclohexanone has secondary carbons, the alkenyllithium species was conveniently formed by elimination of the C,N-dilithiated intermediate obtained upon treating the trisylhydrazone with n-BuLi (Shapiro reaction). None of the above procedures allowed the generation of the more substituted organolithium from 2-methylcyclohexanone. However, the alternative Stille cross-coupling of 34 and 10 afforded 9-cis-1,1-bisdemethylretinoic acid 7. Both Suzuki and Stille coupling reactions took place under mild conditions, and the preservation of the retinoid side-chain geometry was therefore secured.