本論文的研究目的在於利用具有醛官能基的雙環[2.2.2]辛烯酮化合物進行醯基自由基環化及重排反應建立天然物常見的異扭曲烷結構，並探討雙環[2.2.2]辛烯酮骨架上的取代基對於此環化反應的影響。自由基反應前驅物醛類雙環[2.2.2]辛烯酮化合物之雙環結構可藉由掩飾鄰苯醌與丙烯醛進行具有位置選擇性的Diels-Alder反應來建立。接著進行同系化反應就可得到反應前驅物醛類化合物。最後，我們進行硫醇輔助醯基自由基反應得到中間體126接著會經由路徑A或B得到具有異扭曲烷結構的異構物，分別為5-exo-trig環化產物以及3-exo-trig重排產物。以上兩種途徑取決於立體效應、羰基效應以及雙環[2.2.2]辛烯酮化合物上二甲基酮之影響。我們從實驗結果發現從雙環[2.2.2]辛烯酮上酮類官能基對重排反應有非常重要的影響。當將雙環[2.2.2]辛烯酮上酮類官能基還原成羥基後，會使反應無法進行3-exo-trig環化反應，因此不會進行重排反應，而最後經路徑A只得到了5-exo-trig環化產物。當R2及R1位置立體障礙越大以及有二甲基取代，會使反應傾向於路徑B得到較多3-exo-trig重排產物；而當取代基為甲基時，將雙環[2.2.2]辛烯酮上二甲基縮酮酮移除，有利於5-exo-trig環化產物的形成。因此，本論文成功以不同條件控制醯基自由基反應得到5-exo-trig異扭曲烷骨架產物或是3-exo-trig重排異扭曲烷骨架產物。

The research focused on utilizing bicyclo[2.2.2]octone derivatives as an experimental platform to examine the substituent effect on the acyl radical cyclization reaction constructing isotwistane skeleton, which can be found in many natural products. The bicyclo[2.2.2]octone derivatives, prepared for the acyl radical cylization reaction, were obtained from the Diels-Alder reactions and followed by the homologation reactions. We successfully constructed isotwistance skeleton by the thiol-mediated acyl radical cyclization reaction. In the experiments, we found that the reaction tendency is affected by the steric hindrance, carbonyl group effect and the dimethoxy effect. Firstly, the carbonyl group in the bicyclo[2.2.2]octone derivatives is the mainly point to affect the rearrangement reaction. If the carbonyl group was reduced to alcohol, the acyl radical reaction would get only 5-exo-trig product. Secondly, the effect of steric hindrance could be observed when the size of the substituent increased in R2 and R1. The cylization reaction would tend avoid cyclizing to the bulky, so the production of the 3-exo-trig rearrangment product was improved Finally, the effect of the methoxy groups showed that the major product was the 5-exo-trig product. Consequently, we successfully controlled the reaction to favor 5-exo-trig or 3-exo-trig product with different conditions in this methodology.

中文摘要 I
目錄 III
圖目錄 IX
表目錄 XI
流程目錄 XII
縮寫對照表 XV
第一章、緒論 1
第一節 異扭曲烷類天然物之簡介 1
第二節 異扭曲烷骨架之合成方法 2
1-2-1 由烷基自由基5-exo-trig環化反應製備異扭曲烷骨架 2
1-2-2 利用C-H鍵插入合成異扭曲烷骨架 (C-H insertion) 3
1-2-3 利用Pinacol偶合作用合成異扭曲烷骨架 4
1-2-4 分子內Diels-Alder反應合成異扭曲烷骨架 5
1-2-5 以內醛醇反應合成異扭曲烷骨架 5
1-2-6 由醯基自由基合成異扭曲烷骨架 6
第三節 醯基自由基(Acyl Radical)介紹 8
1-3-1醯基自由基的生成 8
1-3-2 Radicals的環化反應 14
1-3-3 醯基自由基在合成上的應用 18
第四節 掩飾鄰苯醌相關反應研究 22
第五節 研究動機 26
第二章、實驗結果與討論 32
第一節 醯基自由基環化反應的醛類前驅物之製備 32
2-1-1 單甲基取代的2-甲氧基苯酚之製備 32
2-1-2異丙基取代的2-甲氧基苯酚之製 32
2-1-3 三級丁基取代的2-甲氧基苯酚之製 33
2-1-4 二甲基取代的2-甲氧基苯酚之製 34
2-1-5 R1為雜原子取代基之2-甲氧基苯酚化合物之製備 36
2-1-6雙環[2.2.2]辛烯酮類化合物的製備 37
2-1-6 同系化反應 40
第二節 醯基自由基環化反應 47
2-2-1 單甲基取代的醯基自由基環化反應的影響 47
2-2-2異丙基取代醯基自由基環化反應的影響 56
2-2-3三級丁基取代對醯基自由基環化反應的影響 58
2-2-4羰基效應對醯基自由基環化反應的影響 65
2-2-5 二甲氧基縮酮對醯基自由基環化反應的影響 68
2-2.6 二甲基取代對醯基自由基環化反應的影響 72
2-2-7 異原子對醯基自由基環化反應的影響 73
2-2-8 溶劑、濃度與輔助硫醇對醯基自由基環化反應的影響 75
第三章、結論與未來展望 78
第四章、實驗部分 84
第一節 一般實驗方法 84
第二節 化合物之實驗步驟與光譜資料 86
4-2-1 苯酚127c之合成 86
4-2-2 苯酚127d之合成 86
4-2-3 苯酚127e之合成 87
4-2-4 苯酚127f之合成 88
4-2-5 苯酚127g之合成 89
4-2-6 苯酚127h之合成 90
4-2-7 苯酚127i之合成 91
4-2-8苯酚127j之合成 92
4-2-9 苯酚127l之合成 93
4-2-10 苯酚127m之合成 94
4-2-11 苯酚127n之合成 94
4-2-12 苯酚127o之合成 95
4-2-13 化合物128a之合成 95
4-2-14 化合物128b之合成 96
4-2-15 化合物128c之合成 97
4-2-16 化合物128d之合成 98
4-2-17 化合物128e之合成 99
4-2-18 化合物128f之合成 100
4-2-19 化合物128g之合成 101
4-2-20 化合物128h之合成 102
4-2-21 化合物128i之合成 103
4-2-22 化合物128j之合成 104
4-2-23 化合物128k之合成 104
4-2-24 化合物128l之合成 105
4-2-25 化合物128m之合成 106
4-2-26 化合物128n之合成 107
4-2-27 化合物128o之合成 108
4-2-28 化合物134a之合成 109
4-2-29 化合物134b之合成 110
4-2-30 化合物134c之合成 111
4-2-31 化合物134d之合成 112
4-2-32 化合物134e之合成 112
4-2-33 化合物134f之合成 113
4-2-34 化合物134g之合成 114
4-2-35 化合物134h之合成 115
4-2-36 化合物134i之合成 116
4-2-37 化合物134j之合成 117
4-2-38 化合物134k之合成 117
4-2-39 化合物134l之合成 118
4-2-40 化合物134m之合成 119
4-2-41 化合物134n之合成 120
4-2-42 化合物134o之合成 120
4-2-43 化合物126a之合成 121
4-2-44 化合物126b之合成 122
4-2-45 化合物126c之合成 123
4-2-46 化合物126d之合成 124
4-2-47 化合物126e之合成 124
4-2-48 化合物126f之合成 125
4-2-49 化合物126g之合成 126
4-2-50 化合物126h之合成 126
4-2-51 化合物126i之合成 127
4-2-52 化合物126j之合成 128
4-2-53 化合物126k之合成 129
4-2-54 化合物126l之合成 129
4-2-55 化合物126m之合成 130
4-2-56 化合物126n之合成 131
4-2-57 化合物126o之合成 131
4-2-58 化合物126a1與126a3之合成 132
4-2-59 化合物126b1與126b3之合成 134
4-2-60 化合物126c1與126c3之合成 135
4-2-61 化合物126d1與126d3之合成 137
4-2-62 化合物126e1與126e3之合成 138
4-2-63 化合物126f1與126f3之合成 139
4-2-64 化合物126g1之合成 141
4-2-65 化合物126h與126h3之合成 142
4-2-66 化合物126i5之合成 143
4-2-67 化合物143g之合成 144
4-2-68 化合物143g1與143g4之合成 145
4-2-69 化合物143h之合成 146
4-2-70 化合物143h1之合成 147
4-2-71 化合物146a之合成 148
4-2-72 化合物146a1與146a3之合成 149
4-2-73 化合物146c之合成 150
4-2-74 化合物146c1與146c3之合成 151
4-2-75 化合物126j1與126j3之合成 152
4-2-76 化合物126k1與126k3之合成 153
4-2-77 化合物126l1與126l3之合成 154
4-2-78 化合物126m1與126m3之合成 155
第五章、參考資料 157
附錄一 化合物之X光單晶繞射數據 161
附錄二 化合物之氫核磁共振光譜圖 168

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