對𝛽,𝛾-不飽和𝛼-酮酯進行具鏡像選擇性的一價銠金屬催化之芳烴化反應:合成掌性四氫萘-2-胺

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2019

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本論文係探討利用1.0 mol %一價銠金屬(劑量以20為基準)與掌性雙環[2.2.1]雙烯配基L20b錯合之催化劑,以及使用0.5當量1.0 M 1,4-二氮雜雙環[2.2.2]辛烷(DABCO,劑量以20為基準)水溶液為添加劑,反應溫度為40 ℃,以甲苯為溶劑之反應條件下,催化不同芳香基硼酸試劑22對𝛽,𝛾-不飽和𝛼-酮酯或𝛽,𝛾-不飽和𝛼-酮醯胺20進行具鏡像選擇性之1,4-加成反應,產出一系列高鏡像選擇性的𝛼-酮酯及𝛼-酮醯胺產物19,產率為47–99%,鏡像超越值為95–>99.5%。藉由此條件,𝛽,𝛾-不飽和𝛼-酮酯20m和苯硼酸試劑22a進行克級一價銠金屬催化不對稱1,4-加成反應,亦能得到𝛼-酮酯ent-19am,產率大於99%,鏡像超越值大於99.5%。 此外,預期以掌性𝛼-酮酯ent-19am經水解反應(hydrolysis)、夫里德耳-夸夫特醯化反應(Friedel-Crafts acylation)、還原反應(reduction)及酉品重排反應(pinacol rearrangement)等一系列反應步驟,生成4-芳基𝛽-四氫萘酮(4-aryl substituted 𝛽-tetralones,9a),再經還原胺化反應(reductive amination),合成出具生物活性之掌性四氫萘-2-胺(tetrahydronaphthalen-2-amines,11)。
This thesis describes an enantioselective addition of arylboronic acids 22 to 𝛽,𝛾-unsaturated 𝛼-ketoesters or 𝛽,𝛾-unsaturated 𝛼-ketoamide 20 in toluene at 40 ℃ in the presence of 1.0 mol % of a chiral Rh(I)-catalyst (the amount was based on 20), in situ generated from [RhCl(C2H4)2]2 and the chiral bicyclo[2.2.1]heptadiene L20b, and 0.5 equiv of 1.0 M aqueous 1,4-diazabicyclo[2.2.2]octane (DABCO, the amount was based on 20) as an additive. The desired 𝛼-ketoesters and 𝛼-ketoamide 19 were generated in 47–99% yields with 95–>99.5% ee’s. A gram scale operation of this reaction of phenylboronic acid 22a to 𝛽,𝛾-unsaturated 𝛼-ketoester 20m could be achieved to afford the desired 𝛼-ketoester ent-19am in >99% yield with >99.5% ee. In addition, the synthesis of 4-aryl substituted 𝛽-tetralones 9a was planned by the hydrolysis of 𝛼-ketoester ent-19am followed by Friedel-Crafts acylation, reduction and pinacol rearrangement. After reductive amination, the bioactive chiral tetrahydro-naphthalen-2-amines 11 were synthesized.

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鏡像選擇性, 一價銠金屬催化, 芳烴化反應, 𝛽, 𝛾-不飽和𝛼-酮酯, 芳香基硼酸試劑, 不對稱加成反應, 掌性, 二氫茚酮, 掌性雙環[2.2.1]雙烯配基, Enantioselective, Rhodium(I)-Catalyzed, Arylation, 𝛽, 𝛾-Unsaturated 𝛼-Ketoesters, Arylboronic acids, Asymmetric addition, Chiral, Indanones, Chiral bicyclo[2.2.1]diene ligands

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