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

Abstract

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.