- 學位論文
利用過渡金屬催化吲哚類衍生物進行烯丙基化反應
Utilizing transition metal-catalyzed allylation of indole derivatives
摘要
吲哚類和吲哚衍生雜環化合物是眾所周知的常見主要架構，其存在於大量有機化合物、藥物和天然產物中，而藥物中有些吲哚類和吲哚衍生雜環化合物含有2,3-二取代結構，這些吲哚衍生物的生物活性與N1和C3位置的官能基化密切相關，因此在吲哚類化合物中N1或C3位置進行烯丙基化反應中官能基化的研究被廣泛探討。此外，也有許多研究顯示在2,3-二取代的吲哚上對N1或C3進行親電子性攻擊以產生新的碳-氮或碳-碳鍵特別困難。 過渡金屬催化劑已成為在有機合成中形成碳-碳，碳-氮，碳-氧和碳-雜原子鍵的主要工具。在有機反應中利用過渡金屬催化進行烯丙基化反應是有效的方法。過渡金屬催化烯丙基化反應引起人們的極大關注，因為該反應可以在多種金屬上完成。 我們結合金屬催化劑挑戰2,3-二取代吲哚與烯丙基試劑進行烯丙基化反應，並在2,3-二取代吲哚類的N1或C3位上建立了烯丙基化系統，成功地完成鉑或鈀催化使吲哚類進行氮-選擇性烯丙基化。此外，考慮到綠色化學，我們選擇在地球上最環保，最自然的材料水做為反應中的溶媒。我們克服在水中進行有機反應，使整個反應順利進行。 在有機反應中直接利用烯丙醇類與吲哚類進行烯丙基化也是重要的問題之一。此論文探討如何處理烯丙醇類中氫氧基斷裂。我們發現一種新的方式，該方法可協助烯丙醇中氫氧基的裂解，並利用鈀催化劑得到高產率的氮-選擇性吲哚類化合物。論文中進行一系列吲哚類的烯丙基化反應，完成綠色化學系統的目標並以簡單的方式克服氫氧基的裂解。
並列摘要
The scaffold of indoles and indole-derived heterocycles is well known as a common structural motif that is found in a large number of organic, medicinal, and natural products. Indoles and indole-derived heterocycles consist of a 2,3-disubstituted construction in medicinal drugs. The biological activities of these indole derivatives are closely associated with functionalization at both N1 and C3 positions. As a result, extensive studies of functionalization have been undertaken to develop catalytic allylation of indole nucleus at N1 or C3 sites. Furthermore, according to a lot of research, it is particularly difficult to electrophilically attack at N1 or C3 site of 2,3-disubstituted indole to produce a new C-N or C-C bond. Transition metal catalysts have been a predominant tool to form carbon-carbon, carbon-nitrogen, carbon-oxygen, and carbon-heteroatom bonds in organic synthesis. The allylation is one of organic reactions catalyzed by transition metal as an efficient method. The allylation reaction of transition metal-catalyzed attracts much attention because the reaction can be completed on a variety of metals. In combination with metal catalysts, we challenged allylation of 2,3-disubstituted indoles with allylic reagents and established the allylated system on N1 or C3 site of 2,3-disubstituted indoles. Successfully achieving the process of N-selective allylation of indoles was catalyzed by platinum or palladium. Also, considering green chemistry, we selected water, the most eco-friendly and natural thing on earth as solvent in the reaction. We overcame the organic reaction in water and proceed the whole reaction smoothly. Direct allylation of indoles with allyl alcohols in organic reaction was also one of important problems. The struggle of how to deal with the cleavage of the hydroxyl group in allylic alcohols was reported in this protocol. We discovered a new strategy to assist the leaving of the hydroxyl group in allyl alcohols and achieve N-selective indoles with high yield by palladium catalyst. This protocol unfolded a series of allylation of indoles, achieved the objective of system in green chemistry and conquered the broken of hydroxyl group in a simple way.
參考文獻
延伸閱讀
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