本文選題：Aza-Michael反應(yīng) + DABCO��； 參考：《上海師范大學(xué)》2017年碩士論文

【摘要】：多數(shù)天然產(chǎn)物和具有生物活性的物質(zhì)中含有γ-氨基醇結(jié)構(gòu)單元,并且其衍生物作為重要的有機(jī)合成砌塊和關(guān)鍵的中間體,而被廣泛用于手性藥物合成。一般通過(guò)不對(duì)稱(chēng)氫化還原Mannich反應(yīng)合成的β-氨基酮,相對(duì)以上傳統(tǒng)方法合成γ-氨基醇,在此我們通過(guò)串聯(lián)Aza-Michael反應(yīng)和不對(duì)稱(chēng)氫轉(zhuǎn)移也可以用于合成該結(jié)構(gòu)單元。Aza-Michael具有操作簡(jiǎn)單和原子經(jīng)濟(jì)性,同時(shí)也包含了不對(duì)稱(chēng)氫轉(zhuǎn)移具有反應(yīng)條件是常溫常壓的特點(diǎn)。本論文主要分為以下兩部分:一、手性二胺釕串聯(lián)邁克爾加成和不對(duì)稱(chēng)氫轉(zhuǎn)移催化合成γ-氨基醇:以苯丙烯酮,芳香胺為原料,通過(guò)串聯(lián)Aza-Michael和不對(duì)稱(chēng)氫轉(zhuǎn)移一鍋合成手性γ-氨基醇。經(jīng)過(guò)反應(yīng)條件的優(yōu)化,催化劑的篩選等,確定了1%的[(S,S)-N-(2-氨基-1,2-二苯乙基)-對(duì)甲苯磺酰胺]氯化(均三甲苯)釕(II)為手性催化劑,甲酸鈉為氫源,0.1mol/l的碳酸鈉和異丙醇體積比為1:1混合溶劑,在40℃條件下以較高的收率和對(duì)映選擇性合成手性γ-氨基醇,而且該催化劑具有良好的底物適用性,通過(guò)底物拓展制備了一系列不同取代基的手性γ-氨基醇,發(fā)現(xiàn)選擇性和收率方面都取得較好的結(jié)果。二、核殼功能負(fù)載型手性二胺釕催化合成γ-氨基醇:在綠色化學(xué)的背景下,結(jié)合1,4-二氮雜二環(huán)[2.2.2]辛烷在Aza-Michael反應(yīng)中的應(yīng)用,考慮到DABCO在對(duì)不對(duì)稱(chēng)氫轉(zhuǎn)移催化劑的不利影響,我們以正硅酸四乙酯、雙(三乙氧基硅烷)乙烷為骨架硅源,以1,4-二氮雜二環(huán)[2.2.2]辛烷硅烷的有機(jī)鹽和(1S,2S)-4-(三乙氧基硅烷基)苯磺�；�-1,2-二苯基乙二胺為功能硅源,通過(guò)水解共聚的方法成功制備核殼功能型材料,然后通過(guò)嫁接的方法將1,3,5-三甲基苯基氯化釕二聚體成功負(fù)載在核殼材料的核內(nèi),通過(guò)通過(guò)13CCP/MAS NMR、XPS、29SiMAS NMR、IR表征來(lái)證明催化劑的負(fù)載成功和催化活性,通過(guò)SEM、TEM、BET、XRD來(lái)觀察制備催化劑的形貌、比表面積、孔徑、金屬含量以及分布等信息。該催化劑成功應(yīng)用于串聯(lián)Aza-Michael和不對(duì)稱(chēng)氫轉(zhuǎn)移一鍋合成手性γ-氨基醇,發(fā)現(xiàn)在立體選擇性和收率方面均取得良好效果,其中最好的對(duì)映選擇性有99%,收率86%。通過(guò)對(duì)17種底物拓展,合成了一系列不同取代基的手性γ-氨基醇,并且該催化劑可以循環(huán)利用。
[Abstract]:Most natural products and bioactive substances contain 緯 -aminoalcohol units and their derivatives are widely used in chiral drug synthesis as important organic synthetic blocks and key intermediates. In general, 尾 -amino ketones are synthesized by asymmetric hydrogenation and reduction of Mannich reaction, and 緯 -amino alcohols are synthesized by comparison with the traditional methods above. Here we can also use the series Aza-Michael reaction and asymmetric hydrogen transfer to synthesize the structure unit. Aza-Michael has the advantages of simple operation and atomic economy. At the same time, the asymmetric hydrogen transfer has the characteristics that the reaction conditions are normal temperature and atmospheric pressure. This thesis is divided into the following two parts: first, chiral diamine ruthenium tandem Michael addition and asymmetric hydrogen transfer catalysis for the synthesis of 緯 -amino alcohol: benzenyl ketone, aromatic amine as raw materials, Chiral 緯-amino alcohols were synthesized by series Aza-Michael and asymmetric hydrogen transfer in one pot. Based on the optimization of reaction conditions and the screening of catalysts, the chiral catalyst was determined as 1% [S _ (2) S _ () -N ~ (2) Amino ~ (2) ~ (2) -diphenylethyl) -p-toluenesulfonamide] chloride (m-trimethylbenzene) ruthenium (鈪，

本文編號(hào)：1841433