本文選題：手性方酰胺　切入點：不對稱催化　出處：《武漢理工大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：不對稱合成是指使用手性物質(zhì)為誘導(dǎo)前手性化合物為原料立體選擇性反應(yīng)構(gòu)建一個或者多個手心中心分子的過程，，它是代替拆分法獲得手性化合物的另一種途徑。這種不對稱合成方法只需要非常少量的手性催化劑就能產(chǎn)生大量的手性產(chǎn)物，并且具有高效性和高立體選擇對映性，在合成手性化合物中應(yīng)用廣泛，前景廣闊。 過去十幾年里，使用有機小分子作為催化劑在不對稱反應(yīng)中發(fā)展十分迅猛，已經(jīng)成為了不對稱催化領(lǐng)域的一個新的研究熱點。其中，手性方酰胺類催化劑在手性硫脲催化劑的基礎(chǔ)上經(jīng)過近年來的研究發(fā)展，成為了極為有效的不對稱合成手性分子的新型大類催化劑，是目前研究的熱點之一。 本文以金雞納堿、1,2-環(huán)己二胺、三氟甲基苯胺和2,3-二甲氧基-3-環(huán)丁烯-1,2-二酮為原料合成了三種不同結(jié)構(gòu)類型的手性催化劑6、18、4。以金雞納堿為起始經(jīng)羥基轉(zhuǎn)化為胺基合成中間體34，三氟甲基苯胺與2,3-二甲氧基-3-環(huán)丁烯-1,2-二酮合成催化劑中間體36，再中間體34與中間體36合成具有金雞納堿衍生的手性方酰胺催化劑6；以(1S,2S)-1,2-環(huán)己二胺為底物與中間體36合成催化劑37，再經(jīng)胺的甲基化等到催化劑18；以(1S,2S)-1,2-環(huán)己二胺此為底物與戊二醛縮合，醋酸硼氫化鈉還原合成（1S,2S）-2-哌啶-1-環(huán)己胺，其與中間體36親核性取代合成手性催化劑4。 論文對催化劑中間體36的合成工藝中投料順序、反應(yīng)溫度和反應(yīng)物料的配比等進行了研究，優(yōu)化了反應(yīng)條件使收率提高約30%。論文對合成中間體36工藝中溶劑、溫度、物料的配比進行優(yōu)化，得到了最佳反應(yīng)時間，反應(yīng)時間縮短了一半。在脂肪胺的親核性取代中，對反應(yīng)溶劑、時間、溫度、底物的配比進行了研究，得到催化劑6、18、4合成的最佳反應(yīng)條件。 在2-羥基萘醌與1,2-二氰基-2-苯基乙烯的不對稱Michael加成反應(yīng)中，研究了三種不同的手性催化劑的催化效果；相比較而言，幾種手性方酰胺類催化劑之間的對映選擇性差別不大。其中，以手性方酰胺催化劑6a的催化效果最好，其對應(yīng)選擇性為25.5%。 在以手性方酰胺催化劑6a為催化劑對2-羥基萘醌與1,2-二氰基-2-（取代）苯基乙烯進行了不對稱催化，以二氯甲烷為溶劑，催化劑量為20%mol，0℃下反應(yīng)24小時，反應(yīng)的收率為34.8%～65.6%，反應(yīng)的對映選擇性為13.4%～25.5%。實驗研究發(fā)現(xiàn)，底物1,2-二氰基-2-苯基乙烯上的苯環(huán)不同的取代基團（給電子、吸電子、空間位阻）幾乎不影響反應(yīng)的立體選擇性。
[Abstract]:Asymmetric synthesis refers to the process of constructing one or more chiral center molecules using chiral substances as the inducer of stereoselective reactions of chiral compounds as raw materials. It is another way to obtain chiral compounds instead of resolution, which requires a very small amount of chiral catalysts to produce a large number of chiral products, with high efficiency and stereoselective enantioselectivity. It is widely used in the synthesis of chiral compounds and has a broad prospect. In the past decade, the use of small organic molecules as catalysts in asymmetric reactions has developed rapidly, and has become a new research hotspot in the field of asymmetric catalysis. On the basis of chiral thiourea catalysts, chiral butylamides have become a new type of catalysts for asymmetric synthesis of chiral molecules, and have become one of the hot spots in recent years. In this paper, a new method was developed for the determination of cinchona alkaloid and 2-cyclohexanediamine. Trifluoromethyl aniline and 2o 3-dimethoxy-3-cyclobutene-2-diketone were used as raw materials to synthesize three kinds of chiral catalysts, 6 / 18 ~ (18) O ~ (4) ~ (4). The intermediates 34, trifluoromethylaniline and 2H ~ (3-) were synthesized by hydroxyl conversion from cinchona base. Synthesis of dimethoxy-3-cyclobutene-2-diketone catalyst intermediate 36, intermediate 34 and intermediate 36 synthesis of chiral galactamide catalyst 6 derived from cinnabine. The catalyst 18 was then methylated by amines, and the substrate was condensed with glutaraldehyde. Sodium borohydride acetic acid was reduced to a chiral catalyst for synthesis of ~ (1) S ~ (2 +) S ~ (2) -piperidine ~ (-1) -cyclohexylamine, which was substituted for 36 nucleophilic intermediates. In this paper, the feeding order, reaction temperature and reaction material ratio of catalyst intermediate 36 were studied. The yield of catalyst intermediate 36 was increased by about 30% by optimizing the reaction conditions. The optimum reaction time was obtained, and the reaction time was shortened by half. In the nucleophilic substitution of aliphatic amine, the reaction solvent, time, temperature and the ratio of substrate were studied. The optimum reaction conditions for the synthesis of catalyst 6 ~ (18) O _ (4) were obtained. In the asymmetric Michael addition reaction of 2-hydroxy-naphthoquinone with 1-dicyano-2-phenylethylene, the catalytic effects of three different chiral catalysts were studied. There was little difference in enantioselectivity between several chiral sulfamide catalysts, among which, the chiral sulfamide catalyst 6a had the best catalytic effect, and the corresponding selectivity was 25.5%. Asymmetric catalytic reaction of 2-hydroxy-naphthoquinone with 1-tri-2-dicyano-2-phenylene was carried out using chiral calcite catalyst 6a as catalyst. The reaction was carried out in dichloromethane as solvent at 20 mol / 0 鈩

本文編號：1636549