I.利用有機膦催化劑誘導碳醯化反應合成β-醯化之α,β-不飽和羰基化合物 II.雙功能金雞納鹼催化不飽和吡唑啉酮與3-高醯基香豆素進行不對稱1,3-偶極環化反應建構螺環吡唑啉酮

Abstract

第一部分: 近年來，本實驗室開發出一系列具有α,β-不飽和羰基的芳香環共振系統化合物作為起始物，並以催化量的非金屬有機膦試劑對β位置親核加成，進行分子內重排得到β位醯化反應 (β-acylation)產物。本篇論文嘗試改變起始物的結構，使用開鏈狀α,β-不飽和羰基查爾酮（Chalcone）衍生物進行β位醯化反應，並成功以同樣具有α,β-不飽和羰基結構的酸酐擴展反應泛用性，最後利用各種控制實驗證明其複雜的反應機制與各項反應條件限制。 爾後延續2014年本實驗室發表的研究，對亦可進行β位醯化反應的羥吲哚與苯並呋喃酮結構進行改良，嘗試移除其上的芳香環系統，只留下單純的五員雜環，保留其上帶有的羰基取代與α,β-不飽和結構，使其具備合理的反應位向，在相似的反應條件下成功以催化量有機膦試劑進行β位置親核加成與分子內重排後，獲得β位醯化吡唑啉酮與噻唑酮產物。

第二部分: 螺環吡唑啉酮（spiropyrazolone）是一種特殊的生物活性骨架，普遍出現於天然物及藥物中。先前關於螺環吡唑啉酮的研究大多侷限於與全碳六原子與異原子五元螺環結構，本篇論文在簡單的反應條件下利用雙功能金雞鈉鹼（cinchona alkaloid）衍生物催化3-高醯基香豆素（3-homoacyl coumarin）衍生物，與另一具有顯著生物活性的吡唑啉酮（pyrazolone）衍生物，進行分子間及分子內兩次麥可1,4-加成反應(Micheal addition)，最終形成全碳五原子螺環吡唑啉酮結構，其上具有五個相鄰的立體中心，且能利用氫鍵控制效應賦予良好產率及鏡像選擇性。

Part I: Recently, our group has developed a novel metal-free β-acylation reaction on a series of cyclic α,β-unsaturated carbonyl derivatives bearing aromatic systems. Catalytic amount phosphine reagent was utilized to add on β-position of α,β-unsaturated carbonyl substrates, affording β-acylation products via intramolecular rearrangement. The current objective of this project is the acyclic compound such as α,β-unsaturated 1,3-diketone and anhydride derivatives. With mechanism studies and control experiments, we proved that the β-acylation is possible in acyclic compounds as well. After successful conversion of the acyclic α,β-unsaturated carbonyl system to β-acylated products, we are further willing to find out the reason for the β-acylation istead of the Wittig reaction. In our reported work in 2014, other substrates can also undergo direct β-acylation such as oxindole and benzofurananone alkylidenes. Herein, we modified the structures of substrates by repleacing the aromatic motifs of oxindole and benzofurananone of relatively. With optimization, the β-acylation of pyrazolone and thiazolone alkylidenes were achieved successfully.

Part II: Spiropyrazolones are special bioactive molecular skeletons which were commonly found in natural products and drug precursors. Recently, the reports on spiropyrazolones are focus on all-carbon six-membered and five-membered ring system with hetero atoms. In our project, cinchona alkaloid derivatives are used to catalyze 3-homoacyl coumarin and α,β-unsaturated pyrazolone derivatives to generate cyclepentane-fused spiropyrazolones via double Michael addition. The desired products bearing five contiguous stereogenic centers were afforded in excellent yields and enantioselectivities without any diastereomer, which is well controlled by hydrongen bonding and steric hindrance.