陳焜銘Kwunmin Chen周俞伽Yu-Chie Chou2019-09-04不公開2019-09-042010http://etds.lib.ntnu.edu.tw/cgi-bin/gs32/gsweb.cgi?o=dstdcdr&s=id=%22GN0697420023%22.&%22.id.&http://rportal.lib.ntnu.edu.tw:80/handle/20.500.12235/100753　　本論文中利用反式-4-羥基-L-脯胺酸衍生之有機催化劑，配合a, a-雙取代醛類，在醛類之a位置進行不對稱氟原子加成反應，並建構一個含氟之四級碳分子，以2-苯基丙醛23為起始物，加入適當的氟試劑，為了得到最高的產率和鏡像選擇性，經過催化劑篩選、挑選最佳溶劑、調整實驗溫度等反應條件的篩選，最後以二氯甲烷(2.0 M)為溶劑，添加20 mol%的催化劑96，反應了1天之後，加入氫硼化鈉將醛基還原為醇基，可得最佳結果為：產率83%，鏡像選擇性40% ee。將氟修飾在藥物分子上，具有改變藥性的作用，近年來已被漸漸地應用在臨床實驗上，證實對許多病症具有療效，顯現氟化產物的應用性。 　　鹵素中的氯原子在有機合成中很常見，特別是含有氯原子的有機分子，是許多天然物全合成步驟中的前驅物，具有發展成其他不同官能基取代的潛力，而具有不對稱的含氯分子，也可在取代的過程中維持其鏡像選擇性，顯現高度的利用價值。想要建構一個不對稱含氯之四級碳分子，利用a, a-雙取代醛類為起始物，進行a-氯原子加成反應。本論文中利用L-脯胺酸衍生之有機催化劑，以2-苯基丙醛23為起始物，選用適當的氯試劑，經過多項反應條件的篩選後，添加20 mol%的催化劑104，在二氯甲烷為溶劑下，只需0.5小時的反應，可得的最佳結果為：產率44%，鏡像選擇性40% ee。　　The development of convenient methods for the construction of important building blocks is main goal in organic chemistry. Enantioselective α-halogenation of ketones/aldehydes is an attractive methodology in organic synthesis because of there synthetic value and importance in pharmaceutics. In this dissertation a general organocatalytic enantioselective α-halogenation of aldehydes have been studied. Series of pyrrolidine-camphor derivatives were employed as organocatalysts for the α-halogenation of α, α-disubstituted aldehydes. Particularly for the α-fluorination of 2-phenyl propionaldehyde 23 was found very efficient catalyst. Reaction was carried out in CH2Cl2, one day using catalyst 96 (20 mol%), the α-fluorinated alcohol product 26 was obtained after NaBH4 reaction in high yield (83%) with moderate enantioselectivity (40%). On the other hand α-chlorination of 2-phenyl propionaldehyde 23 have been studied. Pyrrolidine–camphor derivative 104 was the best catalytic system for the process. Reaction competes only in 0.5 hours in CH2Cl2 and using derivative 104 (20 mol%). The α-chlorinated product 114 was obtained in moderate yield (44%) and moderate enantioselectivity (40%).不對稱有機催化氟化氯化asymmetricorganocatalyticfluorinationchlorination