銅金屬催化氧化碳–氫鍵官能基化與碳–氮鍵生成反應之研究

本論文主要是探討利用銅金屬催化碳-氫鍵的官能基化反應及碳–氮鍵的氧化偶合反應之研究。藉由金屬催化反應，可直接與不具活性之碳–氫鍵進行反應而生成碳–氮鍵，如此可大幅縮短反應步驟與時間成本。在第一章中，我們使用碘化亞銅與聯吡啶所生成之二價銅氧錯合物與2-胺基二苯甲酮反應，順利活化苯環上之sp2碳–氫鍵並藉由自由基途徑進行分子內環化反應，得到吖啶酮衍生物。此反應也可順利擴展至分子間的反應類型，並且藉由此催化方法，成功合成天然物N-Methyl Toddaliopsin A與Arborinine。第二章則著重在利用銅金屬催化苯乙酮與胺基鹽酸鹽進行分子間反應，不僅可順利偶合碳–氮鍵，並且同時進行氧化反應而得到α-酮醯胺衍生物。藉由銅金屬與氧氣作用而產生超氧化物自由基，苯乙酮將被氧化為芳基乙二醛，再與胺類反應而生成α-酮醯胺衍生物。第三章則是延續並結合前兩個章節的概念，透過二價銅氧錯合物催化2'-胺基苯乙酮進行分子內的碳–氫鍵直接氧化胺化反應，成功地同時建構出新的碳–氮鍵與碳–氧雙鍵而得到靛紅衍生物，此方法操作簡便，深具應用價值。第四章的主題則是利用銅金屬催化醇類與胺基鹽酸鹽進行氧化醯胺化反應，將可在一個步驟中同時氧化醇類形成醛類，並接著與胺類反應而得到醯胺衍生物。此研究為第一篇利用銅金屬催化醇類與胺類而得到醯胺產物的研究，取代昂貴的釕、銠與金催化劑，且使用環境友善之氧氣與三級丁基過氧化氫水溶液作為共氧化劑，具有實際應用並大量生產的價值。

關鍵字

銅；催化；碳-氫鍵活化反應；碳-氮鍵偶和

並列摘要

Synthesis of biologically active heterocyclic compounds via transition-metal-catalyzed direct transformation of an inactivated C–H bond into C–N bond is an emerging field in organic synthesis. Mostly these metal-catalyzed reactions are significantly introducing simple conversions and reduce reaction steps and cost. With this regards, this thesis described four new reactions for C–H bond functionalization and C–N bond formation via copper-catalyzed oxidative coupling reaction. In first chapter, we choose CuI and 2,2'-bipyridine to generate Cu(II)OH complex which can successfully proceeding sp2 C–H bond activation and intramolecular cyclization reactions to give acridone products by radical pathway. This reaction can be easily extended to various intermolecular cyclization, total synthesis of N-Methyl Toddaliopsin A and Arborinine with excellent yield. The 2nd chapter focuses on copper-catalyzed intermolecular oxidative C–N coupling reaction of acetophenone with amine hydrochloride salt. The catalytic system proceeds via superoxide radical subsequent acetophenone oxidation to give aryl glyoxal, and then last one react with amine to produce α-ketoamide. Chapter 3 deals with the combination of chapter 1 and 2. The reaction of Cu(II)OH complex with 2'-aminoacetophenone to give isatin via intramolecular direct oxidative C–H amination. This simple method offers an alternative, cheap path way to form isatin through C–N and C–O bond formation. The final chapter describes the copper-catalyzed oxidative amidation of alcohols with amine hydrochloride salts. This reaction condition provides an occasion for the synthesis of different aryl amides by less expensive catalyst.

並列關鍵字

無資料

參考文獻

Chapter 1

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銅金屬催化氧化碳–氫鍵官能基化與碳–氮鍵生成反應之研究

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