路易斯酸催化多取代链状二烯Diels-Alder反应研究

发布时间：2018-01-11 11:23

本文关键词：路易斯酸催化多取代链状二烯Diels-Alder反应研究　出处：《中国科学技术大学》2017年博士论文　论文类型：学位论文

【摘要】：本论文主要研究路易斯酸催化多取代链状双烯在Diels-Alder反应中的反应性能,主要包括以下三部分内容:1.多取代链状二烯与顺/反式构型的α,β-不饱和醛在三氟化硼乙醚催化作用下发生分子间Diels-Alder反应活性差异的研究。我们在探索合成松胞素(Cytochalasans)路线的过程中发现,开链多取代双烯和α,ββ-不饱和醛的顺反异构体的反应活性存在很大的差异。在路易斯酸三氟化硼乙醚催化作用下,具有顺式或者反式构型的α,β-不饱和醛与简单的共轭双烯类化合物的反应活性相差不大。但是对于反应活性较低的开链多取代双烯,使其与顺式构型的α,α,β-三取代的不饱和醛类化合物发生反应,则会得到高产率、高立体选择性的endo-构型环加成产物;而与反式构型的α,α,β-三取代的不饱和醛类化合物完全不反应,利用该反应差异性可以高立体选择性合成含多取代环己烯片段的天然产物分子。2.大位阻路易斯酸三(五氟苯基)硼催化多取代链状二烯与α,β-不饱和醛exo选择性的Diels-Alder反应。在这一研究中,通过对反应条件的探索和优化,我们发现利用大位阻强路易斯酸三(五氟苯基)硼可以催化开链多取代共轭双烯与α,β-不饱和醛发生分子间的Diels-Alder反应,生成exo构型产物。研究还发现,共轭双烯含叔丁基二苯基硅基取代基时,产物的立体选择性最高;另外,α,β-不饱和醛的β-位含缺电子取代基时比含富电子基团时的反应效果好。合成了一系列具有exo构型的环化产物,部分产物通过单晶衍射和2D-NOSEY核磁解析进行了确认。机理研究中,我们认为催化剂与双烯中的取代基之间的空间位阻效应大大削弱了形成endo构型过渡态时的二级轨道重叠效应,促使该反应更容易生成exo构型产物。3.三氟化硼乙醚催化多取代链状二烯与反式构型β-酰基丙烯醛的分子间Hetero Diels-Alder 反应。在该工作中,我们发现路易斯酸三氟化硼乙醚可以催化开链多取代共轭双烯与反式构型的β-酰基丙烯醛发生分子间Hetero Diels-Alder反应。在底物的筛选过程中,我们发现如果双烯化合物中含三异丙基硅基取代基,反应得到较高的产率和立体选择性。另外,共轭双烯中C-4位如果含大位阻基团则会降低反应活性,而在C-3位如果含线性结构的烷烃取代基时,则会促进反应进行。而β-酰基丙烯醛的β位如果含酯基或酮羰基取代基时,反应都可以中等或者较高的产率和高选择性得到杂环Diels-Alder环化产物。
[Abstract]:This paper mainly studies the catalysis of Lewis acid substituted diene chain reaction performance in Diels-Alder reaction, the main content includes the following three parts: chain substituted diene with cis / trans 1. alpha, beta unsaturated aldehydes on Diels-Alder molecular reactivity differences occur between three boron trifluoride ether as catalyst. We explore the synthesis of cytochalasin (Cytochalasans) found that the route in the process of open chain multi substituted diene and alpha, beta beta unsaturated aldehyde CIS trans isomer reaction activity there is a big difference. In three Lewis acid boron trifluoride ether catalyzed with cis or trans alpha, beta unsaturated reactive aldehydes with simple conjugated diene compounds have little difference. But for the low reactivity of open chain substituted diene, the CIS configuration of alpha, alpha, beta three substituted unsaturated aldehyde compounds occur The reaction, will be of high yield, high stereoselectivity of endo- type cyclic adducts; and trans alpha, alpha, beta three substituted unsaturated aldehydes without reaction, the reaction difference can be highly stereoselective synthesis of multi substituted cyclohexene fragments of natural product molecules.2. macroligand Lewis acid three (five fluoro phenyl) catalyzed by boron substituted diene chain reaction of Diels-Alder and alpha, beta unsaturated aldehyde selectivity of exo. In this study, by exploring and optimizing the reaction conditions, we found that the use of sterically hindered Lewis acid three (five fluoro phenyl) boron can catalyze the open chain multi substituted conjugated dienes and alpha, beta unsaturated aldehyde Diels-Alder reaction between molecules, generating exo configurations of the products. It is also found that the conjugated diene containing two tert butyl phenyl silicone substituent, the product stereoselectivity is highest; in addition, alpha, beta unsaturated aldehyde The beta - containing electron deficient substituent reaction than the effect of containing electron rich groups. When a series of exo configuration of cyclization product synthesis, part of the product is confirmed by X-ray diffraction and 2D-NOSEY NMR. The mechanism research, we believe that between the catalyst and the substituents take 16-dpa in space resistance effect greatly weakened the formation of Endo configuration transition state two molecular orbital overlap effect, prompting the reaction easier to generate the product of exo configuration.3. three boron trifluoride ether catalyzed by substituted diene chain and trans beta acyl acrolein Hetero Diels-Alder reaction. In this work, we found that three of Lewis acid fluoride boron trifluoride ether can catalyze open chain multi substituted conjugated diene and trans beta acyl acrolein intermolecular Hetero Diels-Alder reaction. In the process of selecting the substrate, we found that if 16-dpa. Three isopropyl substituent containing silicon substrate, high yield and the selectivity of response. In addition, conjugated dienes in C-4 position if the macroligand group will reduce the reaction activity, and in the C-3 if the linear structure of alkane substituent, will promote the reaction. While beta propylene acyl if a beta aldehyde containing ester or ketone carbonyl substituents, the reaction can moderate or high yield and high selectivity are heterocyclic Diels-Alder cyclization product.

【学位授予单位】：中国科学技术大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：O621.251

【相似文献】