本論文主要為探討以Pd(II)進行金屬催化8-methylquinoline的氟化反應之理論計算研究，所模擬的反應參考一篇的實驗論文，將其路徑分為三階段，每一個階段皆有結構變化、能量圖與NBO圖電荷分析，計算方法選擇為DFT的計算函數b3lyp，搭配基底函數lanl2dz。
    第一階段進行Pd(OAc)2的氧化加成(Oxidative addition)反應，其中包含碳-氫鍵活化(C-H activation)反應，本論文計算模擬得知兩種可能路徑，考慮其金屬配位因素，選擇合理的路徑做後續的模擬與分析。
    第二階段實驗中氟化劑內含氟原子電性偏F+性質，這是一種較少見的方式，由於氟的陰電性極高，要帶正電性是極為不容易的，本論文的模擬結果顯示，氟一旦脫離氟化劑，會快速抓取附近原子上的負電恢復其電性，在此種類似正電性質下，氟能夠較易的脫離氟化劑，以利進行此階段之反應，此外模擬後發現氟化劑之性質顯著影響反應的難易。
    第三階段為還原脫去(reduction eliminative)反應，氟透過還原脫去反應轉移至碳，最後與Pd鍵結之兩個OAc，重新配位生成Pd(OAc)2，而脫去反應物，完成整個反應的模擬。
    本論文計算之結果得知第二階段氟化劑，使F帶類似正電性
質，此為整個反應能否進行的關鍵，依造以F+為主，設計出的不同
氟化劑，將影響此種反應進行的難易，根據其結果，能提供實驗設
計上更多更好的想法。

This thesis is focus on the reaction mechanism of palladium-catalyzed fluorination of 8-methylquinoline. In order to figure out the mechanism and restrictions of the fluorination reaction, we refer a published experimental paper, which divided the pathway into three steps. Each step will have the structural analysis, the NBO analysis and the energy diagram analysis. Besides, geometry optimization was carried out with the DFT method by using B3LYP functional and lanl2dz
   In step 1, we have the Oxidative addition reaction by Pd(OAc)2 which also include C-H activation reaction. We predict two possible pathways by using molecular stimulation calculation. However, there is one pathway has ligand problem so we choose anther reasonable pathway to continue step 1 simulation. 
   In the step 2, the experiment uses the electrophilic fluorinating reagent (F+) to join our reaction. Since fluoride is highly electronegative so it is not easy to make it electrophilic. In our study, we found out that F+ of the fluorination reagent could leave the reagent easily in order to finish the reaction. Besides, the property of fluorinating reagent will affect the reaction difficulty. 
   In the step 3, we have the reduction eliminative reaction. Under this reaction, fluoride can be transferred to the target carbon forming C-F bond. Finally, two OAc bonds of Pd will rearrange to Pd(OAc)2, which can leave the reactant and finish the full simulation pathway.
In conclusion, the fluorinating reagent is the key factor of this reaction. Therefore, developing different kinds of fluorinating reagent can provide more efficient and better fluorination reaction.

目  錄
謝誌		I
中文摘要		II
英文摘要		III
目錄		V
表目錄		VI
圖目錄		VII
第一章	緒論	1
1.1	前言	1
1.2	研究概況	4
1.3	研究動機	13
第二章	研究方法	18
2.1	計算方法及基底函數(Basis set)	18
2.2	Gaussian 09計算指令	19
第三章	結果與討論	22
3.1	Pd(II)催化行氟化反應流程預測	22
3.2	Step 1 Pd(II)的氧化加成反應的探討	24
3.2.1	Pd(II)氧化加成反應預測	26
3.2.2	Pd(II)氧化加成反應的結構探討	27
3.2.3	Pd(II)氧化加成反應的NBO探討	32
3.2.4	Pd(II)氧化加成反應的能量探討	34
3.3	Step 2 氟轉移反應的探討	36
3.3.1	氟轉移反應預測	36
3.3.2	氟轉移反應的結構探討	42
3.3.3	氟轉移反應的NBO探討	51
3.3.4	氟轉移反應的能量探討	58
3.4	Step 3 還原脫去反應的探討	64
3.4.1	還原脫去反應預測	64
3.4.2	還原脫去反應的結構探討	66
3.4.3	還原脫去反應的NBO探討	69
3.4.4	還原脫去反應的能量探討	70
3.5	其他可能的路徑預測	71
3.6	氟化劑之探討	80
3.6.1	tm-pyd、pyd與TEDA之電荷比較	80
3.6.2	tm-pyd、pyd與TEDA之HOMO及LUMO探討	81
第四章	結論	84
參考資料		86

表目錄
表1-1	鹵化物之鹵素與其化合物之鍵能(kJ/mol)	5
表1-2	產物與產率	13
表3-1	氟化劑配上F、Cl、Br之電性(e)	81















圖目錄
圖1-1	含氟的生物活性化合物	2
圖1-2	氟在生物活性劑與材料的功用	3
圖1-3	其他氟化反應	6
圖1-4	氟取代未活化的鹵素芳香環反應	7
圖1-5	金屬催化反應循環	8
圖1-6	氟化反應	10
圖1-7	氟化劑置備反應式	11
圖1-8	加入CA的氟化劑反應式	12
圖1-9	HOAc不離開的反應機制	16
圖2-1	[H3N-H-OH2]+的proton transfer	19
圖3-1	金屬催化反應循環	22
圖3-2	Step 1金屬催化物的氧化加成反應路徑圖	25
圖3-3	Step 1反應路徑結構圖	27
圖3-4	甲基對稱Pd(OAc)2加成的結構優化變化	29
圖3-5	Pd(OAc)2甲基旋轉能障	30
圖3-6	TS2的HOMO-3、TS2的LUMO+4與I2的HOMO-4	31
圖3-7	step 1的NBO分析圖	32
圖3-8	Step 1的能量圖，其能量為在C6H6溶液下之ΔH(ΔG)，溫度為298K	34
圖3-9	TS3到P1之間質子轉移反應	35
圖3-10	加入F-tm-pyd後Step 2-a的反應路徑	37
圖3-11	加入F-pyd後Step 2-b的反應路徑	39
圖3-12	加入F-TEDA後的Step 2-b的反應路徑	40
圖3-13	Step 2-a反應路徑結構圖	42
圖3-14	P1的HOMO與PC1的HOMO	44
圖3-15	Step 2-a的質子轉移反應結構	45
圖3-16	Step 2-b反應路徑結構圖	46
圖3-17	Step 2-c反應路徑結構圖	49
圖3-18	Step 2-a前半的NBO圖	51
圖3-19	Step2-b前半的NBO圖	52
圖3-20	Step 2-c前半的NBO圖	53
圖3-21	N2的NBO圖	54
圖3-22	Step 2-a後半的NBO圖	55
圖3-23	step2-b後半的NBO圖	56
圖3-24	step2-a後半的NBO圖	57
圖3-25	step 2-a的能量圖，其能量為在C6H6溶液下ΔH(ΔG)，溫度為298K	58
圖3-26	I3a到P2a之間的質子轉移反應	59
圖3-27	step 2-b的能量圖，其能量為在C6H6溶液下ΔH(ΔG)，溫度為298K	60
圖3-28	step 2-c的能量圖，其能量為在C6H6溶液下ΔH(ΔG)，溫度為298K	61
圖3-29	step 2-a、step 2-b及step 2-c的能量圖，其能量為在C6H6溶液下之ΔH(ΔG)，溫度為298K	62
圖3-30	Step 3還原脫去反應路徑	64
圖3-31	Step 3反應路徑結構圖	66
圖3-32	I4的HOMO-1圖	67
圖3-33	Step 3的NBO圖	69
圖3-34	Step 3的能量圖，其能量為在C6H6溶液下之ΔH(ΔG)，溫度為298K	70
圖3-35	pathway 2金屬催化物的氧化加成反應路徑圖	73
圖3-36	流程圖	75
圖3-37	反應循環圖	76
圖3-38	F-tm-pyd總反應能量圖	77
圖3-39	F-pyd總反應能量圖	78
圖3-40	F-TEDA總反應能量圖	79
圖3-41	tm-pyd之HOMO-LUMO圖	81
圖3-42	pyd之HOMO-LUMO圖	82
圖3-43	TEDA之HOMO-LUMO圖	82

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