第一部分
本論文研究主要探討利用鈀金屬催化N-苯基吡啶-2-胺與醛類進行鄰位碳-氫鍵活化/芳醯基化反應。江孟帆學長碩士論文中提到以N-苯基吡啶-2-胺衍生物為起始物，苯甲醛衍生物為偶合試劑，醋酸鈀為催化劑，過氧化叔丁醇為氧化劑，1,4-二噁烷為溶劑，於120 oC下反應時間為24小時，得到一次芳醯基化產物與二次芳醯基化產物，產率約為19-94%，如反應式(a)。
本研究是本人利用動力學同位素效應實驗進行分子內及分子間之kH/kD值測量，以及鈀金屬中間體與芳香醛偶合試劑之反應，結合相關文獻推測出一套合理的反應機制。
基於此合成策略，本人進一步將所獲得之芳香基酮產物再次透過碳-氫鍵活化方式合成具有吖啶酮 (Acridanone)之衍生物，如反應式(b)。

第二部分
本論文研究主要探討利用鈀金屬催化吡唑并[1,5-a]吡啶，透過碳-氫鍵活化進行芳香烴化反應。在反應中，添加不同的鹽類(a)氟化銫(CsF)或者(b)碳酸銀(Ag2CO3)進行選擇性的C-3或C-7芳香烴化反應，並分別獲得良好產率。由官能基耐受性實驗，顯示此反應與官能基接有良好的相容性，並提出合理的反應機制。最後，基於此合成策略，有效的合成p38 kinase inhibitors。

Part I
A direct ortho-aroylation of N-arylpyridin-2-amines with aldehydes to afford mono- and di-aroylated N-arylpyridin-2-amines in modest to good yields is presented. In the reaction, palladium(II) acetate, tert-butyl hydroperoxide (TBHP), and 1,4-dioxane were used as the catalyst, oxidant, and solvent, respectively. The synthetic methodology serves good functional group compatibility (Scheme a).
A plausible mechanism of the catalytic C-H aroylation was suggested with the intermolecular and intramolecular experiments in Kinetic Isotope Effect and experiments in palladium intermediate with benzaldehydes.
Based on our methodologies, another-catalyzed C-H bond activation method can be used to get Acridanone (Scheme b).
Part II
A direct arylation of pyrazolo[1,5-a]pyridines with aryl iodides selectively occurring at the C-3 and C-7 positions via palladium-catalyzed C−H activation is described. In these reactions, (a) cesium(I) fluoride and (b) silver(I) carbonate were employed as the additive to afford 3- and 7-arylated pyrazolo[1,5-a]pyridines, respectively, in modest to good yields. These reactions showed good compatibility with functional groups, and the catalytic mechanisms of these reactions were proposed. Finally, the synthetic application on the potent p38 kinase inhibitors was demonstrated.

目錄
中文摘要 iii
Abstract v
表目錄 x
圖目錄 xi
圖譜目錄 xiv
第一章、緒論 1
1-1 利用過渡金屬催化碳－氫鍵活化之歷史介紹 1
1-2鈀金屬催化碳-氫鍵活化反應之為向選擇性與反應價數變化介紹 7
1-2-1導向基團 (directing group)之介紹 7
1-2-2 Pd(II)/Pd(0)進行碳-氫鍵活化機制介紹 10
1-2-3 Pd(II)/ Pd(IV)進行碳-氫鍵活化機制介紹 12
1-3 實驗室論文回顧 13
第二章、主文 19
第一部分 19
2-1 研究動機 19
2-1-1 論文回顧 20
2-2 結果與討論 20
2-2-2 前驅物41的製備 20
2-2-3 前驅物43之合成 21
2-2-4 起始物45之合成 21
2-3 反應最佳化條件探討 22
2-3-1保護基 22
2-4以自由基實驗進行測試 24
2-5動力學同位素效應探討 26
2-6 反應機制探討 28
2-6-1 過去文獻所推測之反應機制 28
2-6-2 Pd中間體製備及X-ray晶體結構圖 29
2-6-3 中間體進行反應機制的測試 30
2-6-4 推測之反應機制 30
2-7 芳香基酮基之吡啶導向基團移除 31
2-8 合成應用性 32
2-9 結論 34
第二部分 35
3-1 研究動機 35
3-1-1 論文回顧 36
3-2 結果與討論 38
3-2-1前驅物質吡唑并[1,5-a]吡啶製備 38
3-3 3號位置取代反應探討 38
3-3-1 3號位置取代反應活化耐受性探討 38
3-3-2 吡唑并[1,5-a]吡啶3號位芳香烴化之機制推測 41
3-4 7號位置取代反應探討 41
3-4-1 7號位置取代反應活化耐受性探討 41
3-4-2 羧基吡唑并[1,5-a]吡啶7號位芳香烴化之機制推測 45
3-5 製備7-芳香烴吡唑并[1,5-a]吡啶化合物 46
3-6 吡唑并[1,5-a]吡啶Bedford’s條件探討 47
3-7 合成應用性 49
3-8 結論 50
第三章、參考文獻 51
第四章、實驗部分 56
4–1儀器部分 56
4–2試藥部分 57
4–3實驗部分 58
4–3–1 前驅物與起始物的製備流程 58
4–3–2 amine上保護基合成步驟 59
4–3–3化合物37之鄰位碳-氫鍵活化苯醯基化反應實驗步驟 62
4–3–4 動力學同位素效應實驗步驟 62
4-3-5 製備反應中間體52實驗步驟 65
4-3-6導引基團移除反應實驗步驟 66
4-3-7碳-氫鍵活化環化反應實驗步驟 66
4-3-8前驅物與起始物的製備流程 67
4-3-9 3號位取代反應實驗步驟 68
4-3-10 7號位取代反應實驗步驟 68
第五章、附錄 74
5–1光譜數據及物理性質 74
5–2 X-ray 單晶繞射數據 89
第六章、光譜附圖 112

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