一價銠金屬催化氮-對甲苯磺醯基之1,2‐二氫喹啉進行不對稱氫芳基化反應
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2020
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本篇論文探討一價銠金屬試劑與掌性雙環[2.2.1]雙烯配基L2a形成之催化劑，於溫度100 ℃且使用環戊基甲基醚為溶劑，並加入甲醇為添加劑的條件下，催化1,2‐二氫喹啉或2H-色原烯12與四芳基硼鈉13進行不對稱加成反應，得到一系列3號位具芳香基之掌性1,2,3,4-四氫喹啉或3號位具芳香基之掌性色原烷14，產率為10–92%，鏡像超越值為87–99%。此外，利用掌性1,2,3,4-四氫喹啉化合物14mh進行去甲基反應及利用掌性1,2,3,4-四氫喹啉化合物14nn經由宮浦硼酸化 (Miyaura borylation)與氧化反應可合成目標產物雌激素乙型受體促效劑 ((R)-3)，前者產率為86%，後者兩個步驟的總產率為52%。
This thesis describes an enantioselective addition of sodium tetraarylborates 13 to 1,2-dihydroquinolines or 2H-chromenes 12 in cyclopentyl methyl ether at 100 ℃ with 5.0 equiv of methanol as an additive in the presence of 3.0 mol % of Rh(I)-catalyst in situ generated from the [RhCl(C2H4)2]2 and chiral bicyclo[2.2.1]heptadiene ligand L2a. The desired products 14 were generated in 10–92% yields with 87–99% ees. In addition, the synthesis of Estrogen receptor β agonist ((R)-3) was achieved by demethylation of compound 14mh in 86% yield. The desired product ((R)-3) was also obtained by Miyaura borylation of compound 14nn followed by oxidation in 52% yield for 2 steps.
This thesis describes an enantioselective addition of sodium tetraarylborates 13 to 1,2-dihydroquinolines or 2H-chromenes 12 in cyclopentyl methyl ether at 100 ℃ with 5.0 equiv of methanol as an additive in the presence of 3.0 mol % of Rh(I)-catalyst in situ generated from the [RhCl(C2H4)2]2 and chiral bicyclo[2.2.1]heptadiene ligand L2a. The desired products 14 were generated in 10–92% yields with 87–99% ees. In addition, the synthesis of Estrogen receptor β agonist ((R)-3) was achieved by demethylation of compound 14mh in 86% yield. The desired product ((R)-3) was also obtained by Miyaura borylation of compound 14nn followed by oxidation in 52% yield for 2 steps.
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鏡像選擇性, 一價銠金屬催化, 氫芳基化反應, 1,2‐二氫喹啉, 2H-色原烯, 四芳基硼鈉試劑, 不對稱加成反應, 掌性, 掌性雙環[2.2.1]雙烯配基, enantioselective, Rhodium(I)-catalyzed, hydroarylation, 1,2-dihydroquinolines, 2H-chromenes, sodium tetraarylborates, asymmetric addition, chiral, chiral bicyclo[2.2.1]diene ligands