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  • 學位論文

1. 以氧釩金屬錯合物進行選擇性醣苷化反應並結合末端炔類化合物合成1,2,3-三唑衍生物產物 2. 以氧釩金屬錯合物催化苯乙烯衍生物與醛類合成互補的β-氧化羰基產物

1. Vanadyl Species activation pathway Enhanced Stereoselectivity of glycosylation and combination with copper powder catalyzed- Azide-Alkyne Cycloaddition (CuAAC) “click” reaction 2. Vanadyl Species-Catalyzed, Complementary β-Oxidative Carbonylation of Styrene Derivatives with Aldehydes

指導教授 : 陳建添
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摘要


我們發展利用氧釩金屬錯合物 (VO(OTf)2) 以過乙醯化的醣來快速的合成具有1,2-反式立體選擇性的疊氮醣苷化反應產物。當我們分別使用VO(OTf)2和TMSOTf當催化劑時,我們利用核磁共振光譜圖中的氫譜來追蹤可以明顯看出其中的差異;在TMSOTf當催化劑時,我們可以在光譜中明顯看alpha形式的訊號(約6.4 ppm)中間產物訊號生成。反觀VO(OTf)2當催化劑時,在光譜中並未發現中間產物生成。利用VO(OTf)2催化疊氮醣苷化反應時的優勢,我們不只將反應運用在單醣、雙醣和三醣上可以獲得較佳的立體選擇性達到(β/α:24/1),進一步可以避免醯基起始物的重排反應和副產物的生成。 第二部分我們將之前合成的疊氮醣苷化反應產物與末端炔類在溫和的條件下利用硫酸氧釩和銅粉間的氧化還原反應,成功的將銅粉氧化成銅一價進行1,3-偶極環化加成反應。主要是利用氧釩金屬可以擁有多種的氧化態從 -3到 +5且反應過程主要透過一個電子的氧化還原過程和適用於多種極性(水和甲醇)、非極性(乙腈)反應溶液下。在這個基礎下,我們將疊氮與末端炔類置於匀相(乙腈)或非勻相(水、甲醇和水與異丁醇)的反應溶劑中;利用硫酸氧釩成功將銅粉氧化成銅一價進行反應成功得到1,2,3-三唑衍生物產物。除此之外我們也嘗試利用含不同配位的官能基氧釩金屬來氧化銅粉進行反應,進而發現氧釩金屬在較鹼性的配位基(硫酸根、乙醯丙酮、醋酸根、異丙醇、胺根)下可以更穩定氧化銅粉形成銅一價進行反應。透過這個氧化還原反應原理,也可明顯說明酸性的離子(三氟甲磺酸和氯離子)扮演一個重要的角色在於形成穩定的銅一價或銅二價。最後我們成功的將反應運用在水中進行,使反應可以更廣泛的運用在生化系統中。 第三部分我們利用VO(OTf)2催化金屬的特性可以有效控制硫糖酐的糖酐化 反應,得到alpha或者beta反構體產物。當我們利用VO(OTf)2-xCH3CN,在低濃度(10 mM)反應系統下和N-碘代丁二醯亞胺活化糖酐對甲苯硫基的離去基,可以得到主要以beta為主的糖酐產物選擇性達49:1。當我們利用VO(OTf)2-xCH3CN (3M in DMF)催化劑和N-碘代丁二醯亞胺活化對甲苯硫基,則得到以alpha反構體為主的產物選擇性達單一反構體為主的產物。值得注意的是當我們減少VO(OTf)2-xCH3CN (3M in DMF)催化劑的當量(0.05當量)時,依舊以alpha產物為主的產物,其選擇性並沒有因催化劑量的減少而有太大的變化。 在第二章節我們利用不同的金屬和氧釩金屬錯合物催化過氧化物TBHP在苯乙烯和苯甲醛偶合反應中,在苯乙烯的beta位置上進行氧化羰基化。其中我們可以有效利用氧釩金屬錯合物上配位基的不同個別獲得在苯乙烯alpha位置水合基或過氧化的加成。當我們利用VO(acac)2當催化劑時,在鹼性配位的官能基主要能獲得alpha-水合beta-羰基化的產物;而當使用VOCl2當催化劑時,則是以alpha-特丁基過氧化beta-羰基為主的產物。因此我們可以透過簡單氧釩金屬上的配位官能基的置換個別獲得兩種互補的產物。除此之外,我們可以利用VO(acac)2催化TBHP在反式beta甲基苯乙烯與對甲基苯甲醛下,獲得順式alpha-水合beta-羰基為主的產物,藉此推測兩種互補的催化耦合反應途徑。

並列摘要


In the first part of this thesis, we reported the synthesis of glycosyl azides from peracetylated sugars (or glycosyl trichloroacetimidates) using VO(OTf)2 as the catalyst which can improve 1,2-trans selectivity to understand the role of this oxometallic species, we monitor the reaction progress by 1H NMR spectroscopic analysis of the reaction mixtures to confirm the different catalytic exerted by VO(OTf)2. An intermediate resulting from glycosyl rearrangement to α-form starting materialwas identified in the catalytic reaction mediated by TMSOTf. This novel vanadyl triflate also provided access to catalyze azidation of various, disaccharides and trisaccharides in high 1,2-trans stereoselectivity and good yields (92-99 %) under mild conditions in CH2Cl2. Not only does VO(OTf)2 enhance β-stereoselective glycosyl azidation but also avoids the rearrangement of C2 acetate group and the formation of orthoester byproducts. The second part is dealt with azide-alkyne cycloaddition (CuAAC) in mild and green conditions by a combination of VOSO4 and Cu(0) for in-situ generation of Cu(I) in aqueous media. Vanadium compounds can exist in oxidation states ranging from -3 to +5 and their interconversion between different oxidation states is achieved by one-electron redox process. Its intrinsic redox nature permits the catalysis of a wide range of organic reactions by judicious combination with suitable metal reductants. Through an extensive survey of various conditions, we have established an effective recipe to generate Cu(I) speceies for the CuAAC reaction in both homogeneous (CH3CN) and heterogeneous (Methanol, t-BuOH/H2O, H2O) solvent systems. In this new click reaction, mild acidic condition plays an important role to stabilize the incipient Cu(I) species and a pronounced ligand effect on the vanadyl species is observed. This new catalytic methodology is attractive because it can be applied to aqueous solution which is important in biological systems at ambient temperature and physiologic pH conditions. In the third part, we have disclosed an elegant and pragmatic catalytic system by using VO(OTf)2 catalyst for 1.2-trans β-selective and 1,2-cis α-selective glycosylationof thioglycosides. The catalytic strategy described herein can achieve stereospecific glycosylation in excellent yields. When low-concentration (10 mM) mixed solvent systems (CH2Cl2-CH3CN-EtCN) with N-Iodosuccimide (NIS, 1.25 equiv) as the activator was employed, preferential 1.2-trans glycosides(-selectivity) was attained. When VO(OTf)2-xCH3CN was used as a solution in DMF for catalytic glycosylation, highly 1,2-cis (α-selectivity) glycosylation was achieved. Finally, a reduced loading of VO(OTf)2-xCH3CN (3M in DMF) to 0.05 equiv still led to efficient catalysis and 1,2-cis -selective glycosylation can still be maintained. In the second chapter of this thesis, a series of oxometallic species and metal acetylacetonates (acac) was examined as catalysts for oxidative beta-carbonylation of styrenes with benzaldehyde by using t-butylhydroperoxide as co-oxidant and trapping agent in warm acetonitrile. Among them, VO(acac)2 and vanadyl(IV) chloride were found to be the only two catalyst classes to achieve the cross-coupling processes by judicious turning the ligand electronic attributes, leading to β-hydroxylation and β-peroxidation of styrenes, respectively, in a complementary manner. Mechanistic studies indicated that vanadyl associated, acyl radicals generated by t-butoxy radical-assisted, homolytic cleavage of aldehyde C-H bond were involved in the tandem processes with exclusive syn diastereoselectivity in the case of -methylstyrene.

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