兰州大学机构库 >生命科学学院
官能团化手性炔丙醇的不对称合成研究及其在昆虫信息素不对称全合成中的应用
Alternative TitleAsymmetric Synthesis of Functionalized Chiral Propargylic Alcohols and Application in Total Synthesis of Insect Pheromone
林利
Thesis Advisor王锐
2009-05-28
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name博士
Keyword不对称催化 平均对映选择性反转率 手性炔丙醇 炔基锌 γ-丁内酯 全合成
Abstract手性炔丙醇结构存在于许多具有生物活性的天然产物中,并且也是许多手性药物的重要合成前体。由于催化末端炔对羰基化合物的不对称加成在制备手性炔丙醇的同时,能够构建一个碳碳键和一个手性中心,因而该领域的研究受到了研究者的广泛关注,有大量的研究工作见报道。本论文即针对现有催化体系的底物局限性、催化效率低、应用研究少等展开研究: 1、 我们将简便合成的磺酰胺基醇配体-钛催化体系应用于催化丙炔酸甲酯对各类芳香醛及脂肪醛的不对称加成取得了理想的结果。以DME为添加剂使不对称合成手性γ-羟基-α,β-炔酸酯的反应条件更加温和、易于操作,避免了剧毒物质(HMPA)的使用。与其他催化体系进行充分对比,指出磺酰氨基醇配体中的磺酰基硫氧作为路易斯碱在反应过程中起到了重要的作用。 2、 对不同方式负载的手性催化剂在不对称炔加成中的应用比较后发现,直链聚苯乙烯负载的磺酰胺基醇-钛体系能够高效的催化苯乙炔对芳香醛的不对称加成,以三乙胺为添加剂能够大大提高催化剂的反转率,催化体系效率不仅较其单体大大提高,且高于现有其他各类催化体系。负载的配体能够方便的循环利用六次而催化活性无显著丧失。并与第一部分的研究共同阐明了不同类型的路易斯碱在炔对醛加成中的不同作用。 3、 我们首次提出以配体(或催化剂)的平均对映选择性反转率(E-TOF)来综合评价不对称催化体系的有效催化效率。这一概念包括反应产率、对映选择性、配体(或催化剂)用量以及反应时间四个重要反应参数,不仅适用同一反应不同催化体系的横向综合性评价,而且适用于某一特定反应催化体系的优化过程,有助于研究人员选择最佳的反应条件。 4、 我们发展了以手性γ-羟基-α,β-炔酸酯为关键中间体完成了手性γ-丁内酯类天然产物的对映立体选择性全合成,该关键中间体能够以我们的催化体系方便的对映选择性合成,之后的官能团转换方法成熟,易于操作,无需进行繁琐的官能团保护和脱保护过程,绿色经济。由这一合成策略,我们由最简单的原料经过3-5步即可以84%的ee值方便的得到所需关键中间体,经过三步转换即以大于87%的总产率得到结构类似的昆虫信息素(4S, 5Z)-1和(4R, 9Z)-2。
Other AbstractChiral propargylic alcohols present in many bioactive natural products. These building blocks are also important pharmaceutical intermediates. The asymmetric alkynylation of carbonyls is proved to be one of the most powerful procedures for organic synthetic chemistry, where the formation of one carbon-carbon bond and one chiral center of propargylic alcohol can be achieved in one step, and has attracted organic chemists’ most attentions. Plenty of works have been reported in recent years. This thesis mainly focuses on overcoming the substrates limition of the present catalytic systems, low catalytic efficiency, and application in total synthesis. 1. Conveniently synthesized sulfonamide alcohol titanium complex has been used to catalyze the asymmetric addtition of methyl propiolate to various aromatic and aliphatic aldehydes with high enantioselectivity. With 1,2-dimethoxyethane (DME) as an additive, the reaction proceeded under mild condition to gave the highly functionalized γ-hydroxy-α,β-acetylenic esters, and highly toxic reagent was avoided. Compared with other catalytic systems, the sulfonyl oxygen atoms of the sulfonamide alcohol played an important role in the catalytic addition as an Lewis base. 2. Different supported chiral ligands have been used to catalyze the asymmetric alkynylation. the asymmetric addition of phenylacetylene to aromatic aldehydes can be effectively catalyzed by linear polystyrene supported sulfonamide alcohol-Titanium complex. Additive TEA can highly accelerate the turnover frequency of the catalyst. The efficiency of this catalytic system is much higher than that of its mono-analogue or any other homogeneous catalytic systems. The easily recoverble linear PS-supported ligand has been reused six times without loss of catalytic activity. In combination of the former studies, it is found that different type of Lewis base exhibit different influences. 3. For the first time, we introduced the average enantioselective turnover frequency (E-TOF) in the asymmetric phenylacetylene addition to aromatic aldehydes to evaluate the positive efficiency for different catalytic systems in principle which taking enantioselectivity, yield, catalyst loading, as well as reaction time into account. The E-TOF will also be feasible and practical to assist chemists in screening the optimal reaction condition or evaluating the overall efficiency of different catalytic systems for a specific asymmetric reaction. 4. For the first time, we explored...
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Language中文
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/221303
Collection生命科学学院
Recommended Citation
GB/T 7714
林利. 官能团化手性炔丙醇的不对称合成研究及其在昆虫信息素不对称全合成中的应用[D]. 兰州. 兰州大学,2009.
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