一價銠金屬/雙環[2.2.1]雙烯配基催化烯醇醚基三氟硼酸鉀鹽與芳香基亞胺進行不對稱加成反應及藥物(S)-達伯西汀的合成應用
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2016
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Abstract
本論文利用一價銠金屬與本實驗室開發之掌性雙環[2.2.1]雙烯配基L1e的催化系統，使各式烯醇醚基三氟硼酸鉀鹽試劑 53a‒f與芳香基亞胺10a‒o進行不對稱催化加成反應，在100 oC下以甲苯作為溶劑，添加100 wt%研磨過分子篩 (MS 4Å)，反應六小時，可合成出具有高鏡像選擇性的新型掌性烯丙基胺骨架之產物34，其產率為21%到83%，鏡像超越值為94%到>99.5% ee。
在合成應用上，利用合成出的新型掌性烯丙基胺化合物34ae，經由簡單的官能基轉變，就可以合成出市售藥物 (S)-Dapoxetine (60)。
This thesis describes the asymmetric synthesis of optically active amines bearing enol ethers. In the presence of 5.0 mol% of the Rh(I) catalyst comprising chiral diene ligand L1e, the enantioselective addition of potassium enol ether trifluoroborates (53a‒f) to aldimines bearing N-Ts protecting groups afforded the desired allylic amines in 21– 83% yields with 94–>99.5% ee. The method was applied to the total synthesis of (S)-Dapoxetine (60).
This thesis describes the asymmetric synthesis of optically active amines bearing enol ethers. In the presence of 5.0 mol% of the Rh(I) catalyst comprising chiral diene ligand L1e, the enantioselective addition of potassium enol ether trifluoroborates (53a‒f) to aldimines bearing N-Ts protecting groups afforded the desired allylic amines in 21– 83% yields with 94–>99.5% ee. The method was applied to the total synthesis of (S)-Dapoxetine (60).
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達伯西汀, 一價銠金屬, 三氟硼酸鉀鹽, 掌性, 烯丙基胺, 不對稱催化, Dapoxetine, Potassium trifluoroborates, allylic amine, Chiral, Rhodium, diene ligand, Enantioselective