本論文提供「環閉合置換反應（ring closing metathesis, RCM）後產生之烯烴進行選擇性衍生化的方法」，並藉由鈀金屬催化甲酸還原反應（palladium catalyzed formate reduction）來達成此一目的。我們使用二氫吡喃（dihydropyrane）雜環 4 為模型，以改變甲酸還原反應之配位基的方式，尋找適用於環閉合置換後的含氧六員雜環進行甲基烯衍生之最佳條件。 為了探討此方法於有機合成上的實用性，我們更進一步地合成了4-及5-取代哌啶甲酸（pipecolic acid）的前驅物 28a、29、35、36 及 38。其關鍵步驟在於「環閉合置換反應來組成哌啶甲酸六員雜環的基本骨架，並串聯鈀金屬催化甲酸還原反應進行甲基烯衍生」；而哌啶甲酸2 號位置上的掌性中心，則藉由 Dellaria 教授的「光學輔助胺基乙酸烯醇合成子之立體選擇烷化反應stereoselective alkylation）」及 Royer、Husson 團隊的「去質子/光學輔助立體選擇質子化反應」進行不對稱合成的控制。 The method for regioselective palladium-catalyzed formate reduction of allylic benzoate formed by ring closing metathesis was developed. We used 2,2-diphenyl-tetrahydro-2H- pyrane 4 as the model compound, and found an optimized condition of formate reduction by screening several ligands. 4- or 5-Substituted pipecolic acid precursors 28a, 29, 35, 36 and 38, which are biologically active compounds or their precursors, were synthesized by this method. The key steps of these syntheses involve the formation of the skeleton of pipecolic acids with ring closing metathesis and transformation of endo-olefins with palladium-catalyzed formate reduction. We used stereoselective alkylation and deprotonation/stereoselective protonation to control the generation of chiral center in these pipecolic acid precursors.
