本研究中，我們利用鈀錯合物分別進行一系列的鄰溴肉桂酸酯衍生物與苯稠環-氧雜降冰片二烯之外消旋和不對稱[3+2]環化反應。經由鈀(II/0)催化劑，17種不同的手性配體，10種不同的(共)溶劑，以及矽烷添加劑和碳酸鹼，在60-80 ℃的反應溫度中，系統性的測試出最佳化之條件，最終在80 ℃下分別使用醋酸鈀搭配dppf之雙磷配體以及(R)-DM-BINAP之手性二萘雙磷配體，並以乙腈作為溶劑為最佳化之條件，形成帶有環外雙鍵含烯酸酯單元的外消旋及光學活性之茚滿-稠合氧雜降冰片烷衍生物。其中包括10種不同的酯基受質: 非芳香族酯基、芳香族酯基，苯環取代基，在外消旋反應中，產率介於32-95%，順反幾何異構物選擇性 (Z/E ratio) 介於80/20至僅有Z異構物間；在不對稱反應中，產率介於34-76%，鏡像選擇性介於14-43% ee，而順反幾何異構物選擇性 (Z/E ratio) 介於55/45至僅有Z異構物間。此外，外消旋產物的環外雙鍵含烯酸酯單元可經由Pd/C進行外向加氫反應，並與通過Rh(I)-dppf催化反應直接合成的產物，互為C11上的一組差向異構物對。
最後，我們經由醋酸鈀(II)催化劑和Josiphos SL-J001-1之手性雙磷配體，5種不同溶劑，5種變溫反應，矽烷添加劑，並搭配鄰三氟甲磺酸酯基肉桂酸酯衍生物，再優化了吳庭萱 (Ting-Hsuan, Wu) 學姊的論文中，以氧雜降冰片烯稠合順式二苯乙烯/芴螺旋體為模板的[3+2]不對稱環化反應條件，並進一步測試9種受質，產率介於41-74%，鏡像選擇性介於46-77% ee。

In this thesis, we employed bivalent palladium complexes to perform a series of racemic and asymmetric [3+2] cascade cyclizations between o-Br-substituted cinnamate (CM-Br) derivatives and benzo-fused 7-oxa-norborna-diene (Bz-OND). Under a systematic study on Pd(II/0) catalysis, 17 different chiral ligands, 10 different solvents (including one co-solvent), silane additives, and carbonate bases within reaction temperature range of 60-80 °C, we determined the optimal conditions: Pd(II) acetate with the dppf bidentate ligand and the (R)-DM-BINAP chiral bidentate ligand, respectively in acetonitrile at 80 °C, providing a series of desired racemic and optically active Bz-OND-fused indanes bearing 1-carbonylmethylidene (CBM) unit. Furthermore, we conducted tests on 10 different ester substrates, including aliphatic, aromatic, and 4-substituted or 5-substituted methyl cinnmates. The racemic cyclization products were afforded in a range of 32-95% yield, and the Z/E selectivity was in a range of 80/20 (benzyl, 4-Me) to exclusive Z (methyl, t-butyl, 2-naphthyl, 5-F). The optically active cyclization products were afforded in 14-43% ee, with yields ranging from 34 to 76%, and the Z/E selectivity was in a range of 55/45 (1-naphthyl) to exclusively Z (t-butyl, 2-naphthyl).

Additionally, exclusive hydrogenation from the exo-face of the CBM alkene units can be readily done by Pd(0)/charcoal in EtOAc, affording the product complementary a C11 to the one from direct Rh(I)-catalyzed cyclization.

Finally, under a systematic study on Pd(II) acetate catalyst and the chiral bidentate diphosphine ligands, including Josiphos SL-J001-1, 5 different solvents, five temperature variations, silane additives, and particularly effective combination with o-triflyloxy-substituted cinnamates derivatives, we re-optimized the conditions of palladium-catalyzed [3+2] asymmetric cascade cyclization for the optically active indenes bearing spirally configured, benzo-fused cis-stilbene/fluorene templates, described previously in the Ting-Hsuan, Wu’s thesis. We further tested 9 different substrates, affording the corresponding product with yields in a range of 41-74% and in 46-77% ee.

中文摘要------------------------------------------------------I
Abstract-----------------------------------------------------III
謝誌----------------------------------------------------------V
式目錄--------------------------------------------------------XI
表目錄--------------------------------------------------------XIV
圖目錄--------------------------------------------------------XVI
縮寫對照表----------------------------------------------------XVIII
第壹章、緒論------------------------------------------------------1
第一節、氧雜降冰片烯衍生物在合成及催化反應的應用---------------------1
第二節、茚滿衍生物在合成及催化反應的應用----------------------------7
第三節、研究動機--------------------------------------------------21
第貳章、結果與討論------------------------------------------------22
第一節、苯稠環-氧雜降冰片二烯在鈀(II)催化下進行外消旋[3+2]環化反應---22
第二節、外消旋[3+2]環化反應所得環外雙鍵產物12aa進行氫化反應----------26
第三節、氫化產物13aa與苯稠環-氧雜降冰片二烯在銠(I)催化外消旋[3+2]環化反應所得產物13ba的相關光譜及 X-ray 單晶繞射結果--------------------------27
第四節、苯稠環-氧雜降冰片二烯在鈀(II)催化下進行不對稱[3+2]環化反應---30
第五節、順反幾何異構物選擇性 (Z/E ratio) 之探討--------------------52
第六節、推測的催化循環 (以生成Z異構物產物為例)----------------------55
第七節、氧橋降冰片烯苯並融環順式二苯乙烯/芴螺旋體在鈀(II)催化下進行不對稱[3+2]環化反應的再優化--------------------------------------------57
第八節、推測的催化循環--------------------------------------------72
第九節、結論-----------------------------------------------------74
第參章、分析儀器、實驗步驟及光譜數據-------------------------------76
第一節、分析儀器-------------------------------------------------76
第二節、實驗步驟及光譜數據----------------------------------------79
參考文獻--------------------------------------------------------223
附錄壹、核磁共振光譜圖--------------------------------------------S1
附錄貳、X-ray單晶繞射結構解析數據---------------------------------S85

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