以α,β-不飽和丁內醯胺衍生物與1,2-雙醯基乙烯類及香豆素衍生物進行有機催化Michael加成反應之研究 Investigation of the Organocatalytic Vinylogous Michael Addition of α,β-Unsaturated γ‑Butyrolactam to 1,2-Diacylethylenes and Coumarin derivatives

Date
2015
Authors
劉孟憲
Liu, Meng-Hsien
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Abstract
丁內醯胺骨架的化合物廣泛的存在於天然物中,其擁有很重要的生物活性,並在有機合成上的運用也是相當的豐富,本篇論文共有兩個主題,皆是以 α,β-不飽和丁內醯胺衍生物1為親核試劑進行研究,探討其對1,2-雙醯基乙烯23 (第一章)及香豆素衍生物57 (第二章) 進行有機催化Michael 加成反應。 在第一章,我們成功的使用奎尼丁-硫脲衍生物催化α,β-不飽和丁內醯胺1衍生物進行Michael 加成反應,在1,2-雙醯基乙烯23建構出兩個相鄰三級碳的光學中心,並拓展其取代基的種類,增加其應用性,產率最高可達95%,非鏡像異構物比率>25:1,鏡像超越值可達99%。 在第二章,我們使用香豆素衍生物56做為親電子試劑,合成二氫香豆素衍生物57,有別於過去α,β-不飽和丁內醯胺1的Michael加成反應研究中,大部分的反應中心為γ位置,本研究主題的化學選擇性為α位置的加成,其產率可以達到99%,並具有高非鏡像選擇性 (dr>25:1)。並且發展了一個新的反應路徑合成在α位置加成的α,β-不飽和丁內醯胺衍生物58。
The γ-butyrolactam derivatives (5-substituted 3-pyrrolidin-2-ones) belong to a family of structurally diverse natural compounds with remarkable biological activities which also signify their importance in organic chemistry. There are two topics of this thesis, which are based on the use of α,β-unsaturated butyrolactam derivatives 1 as the nucleophile : investigation of asymmetric organocatalytic Michael addition of γ-butyrolactam 1 to ene-diones 23 (Chapter 1), and coumarin derivatives 56 (Chapter 2) In the chapter 1, we have demonstrated an efficient protocol using the quinidine-derived bifunctional catalyst for a highly efficient Michael addition of α,β-unsaturated γ-butyrolactam 1 to various ene-diones 23 to provide synthetically useful compounds 24. The products were obtained with high diastereo- and enantioselectivities (up to >25:1 dr and 99% ee) containing adjacent tertiary stereocenters In the chapter 2, a highly efficient direct vinylogous Michael addition–isomerization reaction of α,β-unsaturated γ-butyrolactam 1 and coumarin derivatives 56 by using a basic catalyst was achieved. The Morita–Baylis–Hillman type adducts 57 can be obtained in high yields (up to 99% yield) and with excellent diastereoselectivities (dr >25:1). Furthermore, a novel synthetic route for the efficient synthesis of γ-butyrolactam derivatives 58 has been demonstrated.
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Keywords
有機催化, α, β-不飽和丁內醯胺, Michael加成反應, Organocatalytic, Vinylogous Michael Addition, α, β-Unsaturated γ‑Butyrolactam
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