銠金屬(I)/掌性雙烯配體催化有機芳香和烯基硼酸試劑對β-吡唑-1-基 丙烯酸酯行1,4不對稱加成反應：Ruxolitinib的形式合成
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2015
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Abstract
本論文利用一價銠金屬和雙環[2.2.1]掌性雙烯配基（L2a）形成之錯合物為催化劑，在甲醇當溶劑下以三乙基胺作為添加劑加熱至60 °C，催化各種不同的芳香環和烯基硼酸試劑與β-吡唑-1-基丙烯酸酯類化合物進行不對稱1,4-加成反應，合成出一系列具有掌性中心β-芳香基和烯基取代化合物，其產率最高可至99％，鏡像超越值最高也可達到99％ ee。
在合成應用上，確立了一系列芳香基和烯基加成產物具有高度的鏡像超越值之後，利用建構出來的掌性化合物作為合成的起點將不同的官能基骨架相續接上並設計出一種 JAK酶抑制劑及抗血癌藥物Ruxolitinib的合成策略。
In this thesis, a conjugate addition reaction, catalyzed by 5 mol% of the Rh(I)/L1a, of aryl- and alkenyl-boronic acids with β-pyrazole acrylate, where the pyrazole is substituted or non-substituted, provided the corresponding addition products in 26 − 98% yield and 88 − 99% ee. The method was applied to the formal synthesis of Ruxolitinib, a Janus kinase（JAK）inhibitor that is used in the treatment of myelofibrosis.
In this thesis, a conjugate addition reaction, catalyzed by 5 mol% of the Rh(I)/L1a, of aryl- and alkenyl-boronic acids with β-pyrazole acrylate, where the pyrazole is substituted or non-substituted, provided the corresponding addition products in 26 − 98% yield and 88 − 99% ee. The method was applied to the formal synthesis of Ruxolitinib, a Janus kinase（JAK）inhibitor that is used in the treatment of myelofibrosis.
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產率, 鏡像超越值, yield, ee