【作者】 李云霞；

【导师】 王全瑞；

【作者基本信息】 复旦大学 ， 有机化学， 2007， 博士

【摘要】 σ重排反应是有机化学中的一个重要反应。由于其独特的立体选择性及区域选择性,并可实现分子结构重组及碳-碳键的形成,进行一些传统反应难以实现的分子特定骨架的构建;因此被广泛应用于一些天然产物及目标分子的合成中,国际上有许多关于这类重排反应的理论及应用研究。而σ重排反应的串联反应,由于其高效、简洁的特点迎合了现代有机化学发展的主流方向,也开始成为研究的热点。本论文研究的σ重排反应主要为Ireland-Claisen重排与[2,3]-Wittig重排。本论文第一部分工作对不饱和羧酸烯丙基酯类化合物的Ireland-Claisen重排进行了深入的研究,并将Ireland-Claisen重排产物的衍生化应用于潜香物质的合成,主要有以下四个方面:一、研究了丙烯酸烯丙酯类化合物的Ireland-Claisen重排反应。将Baylis-Hillman反应条件与Ireland-Claisen重排反应有机结合起来,创建了一条新颖的DABCO-催化的丙烯酸烯丙酯类化合物的Ireland-Claisen重排反应路线;另外在研究反应应用范围及选择性的同时,使用一些价廉易得的香料分子为原料进行底物7a-o的合成,然后重排得到系列α-亚甲基-γ,δ-不饱和羧酸类化合物19a-m。二、研究了DBU-促进的烯酸烯丙酯类化合物的Ireland-Claisen重排反应。利用DBU作为烯醇化碱,对含有活泼质子的烯酸烯丙酯类化合物9-16的Ireland-Claisen重排进行了系统的研究,创建了一条新颖的DBU-促进的Ireland-Claisen重排/异构化串联反应及Ireland-Claisen重排/Cope重排的串联反应路线。通过对其应用范围的考察,发现此重排序列可以广泛应用于各种类型的底物,实现了多类取代不饱和共轭羧酸类化合物23a-f,25,29a-f,31a-c,33及35a-g的制备。三、研究了不饱和羧酸炔丙酯类化合物的Ireland-Claisen重排反应。首先在进行DABCO-催化的丙烯酸炔丙酯类化合物18b-d的Ireland-Claisen重排反应的同时,于反应体系中分别加入亲二烯体40a-f捕获重排得到的连二烯中间体,一步反应获得了单一区域选择性的Diels-Alder环加成产物41a-i,从而创建了一条新颖的丙烯酸炔丙酯类化合物的Ireland-Claisen重排与Diels-Alder环加成的串联反应路线。其次,以含有活泼质子的烯酸炔丙酯18e-k为底物,在DBU为烯醇化碱、TMSCl为硅试剂的条件下,底物18e-h发生了Ireland-Claisen重排/异构化串联反应,得到完全共轭的三烯类化合物42a-b及43a-b;而以己二烯酸炔丙基酯18i-j为底物时,重排/异构化后的产物进一步发生电环化等反应最终得到芳构化产物——取代苯甲酸类化合物44a-b。这为合成此类取代模式的芳香化合物提供了一条新颖的路线。四、基于合成香料化学目前发展的现状,以香料的分子结构对香气影响的一些规律为指导,对所获得的部分Ireland-Claisen重排产物羧酸进行结构修饰,合成了系列潜香分子46a-s,47a-b,48a-d及49a-e,并进行了评香。发现此类分子大多具有水果、花香的味道。本论文第二部分工作对利用[2,3]-Wittig重排构建叔醇类化合物进行了初步尝试研究。通过对一些底物的[2,3]-Wittig重排条件的摸索,发现其中烯丙基末端没有取代基的醚类底物52a与56a可以发生[2,3]-Wittig得到叔醇类化合物57a与58a,而有取代基的烯丙基醚类底物52b与56b在探索多种条件下均未能发生反应。对此[2,3]-Wittig重排反应的应用范围及局限性还有待进一步深入研究。更多还原

【Abstract】 Sigmatropic rearrangement is an important reaction in organic chemistry. Because of its special stereoselectivity and regioselectivity, realization of molecule’s structure reorganization and carbon-carbon bond’s formation, establishing compound’s particular framework instead of some conventional reaction, it has been widely used in the synthesis of a diverse range of natural products and other targets. Several research of theoretics and application about sigmatropic rearrangement have been reported. Again, tandem reaction of sigmatropic rearrangement and other reaction has also begun to become research focus because of it’s high-efficiency and concision, meeting the orientation of modern organic chemistry.Sigmatropic rearrangement studied in this thesis mainly includes Ireland-Claisen rearrangement and [2,3]-Wittig rearrangement.In part 1 of this thesis, we investigated Ireland-Claisen rearrangement of allyl esters of unsaturated acids systemically, and applied the rearranged products for derivation to some fragrant molecules; Four topics are addressed, which are:1. We studied Ireland-Claisen rearrangement of allylic acrylates. Combined Baylis-Hillman reaction condition with Ireland-Claisen rearrangement, we have established a novel DABCO-catalyzed Ireland-Claisen rearrangement of allylic acrylates. Furthermore, in the course of studying the scope and limitations, we empolyed readily available molecules 7a-o as the starting materials. The rearranged products represents new unsaturated compounds 19a-m after rearrangement.2. We studied DBU-mediated Ireland-Claisen rearrangement. Using DBU as the base for enolization of allylic esters of unsaturated acids 9-16, we found a novel DBU-mediated tandem Ireland-Claisen rearrangement /isomerization reactions and established a consecutive Ireland-Claisen rearrangement /Cope rearrangement. By investigation of its scope and limitations, we found the protocol could work well for a wide variety of substrates to provide polyfunctionalized conjugated carboxylic acids 23a-f, 25, 29a-f, 31a-c, 33 and 35a-g .3. We studied Ireland-Claisen rearrangement of propargylic esters of unsaturated acids. First, when operating the DABCO-catalyzed Ireland-Claisen rearrangement of propargylic acrylates 18b-d, we added dienophiles 40a-f in the reaction system to capture the rearranged allenes products respectively. The Diels-Alder adducts 41a-i were obtained with complete regioselectivity. Thus a novel tandem Ireland-Claisen rearrangement /Diels-Alder reaction process with propargylic acrylates has been developed. Second, using DBU as the base for enolization of propargylic esters of unsaturated acids 18e-k, we developed a tandem Ireland-Claisen rearrangement /isomerization reactions. It has been shown that the reaction sequence affords triene molecules 42a-b and 43a-b in moderated to high yields. Interestingly, with allyl hexa-3,5-dienoates 18i-j as the substrate, the rearranged products underwent further aromatization to give uniquely substituted benzyl acids 44a-b. This offers an efficient synthetic way to this kind of aromatic acids.4. Based on the concepts of fragrance chemistry, under the guidance of molecules’ structure and odour relationships, we synthesized a list of potential odorants 46a-s, 47a-b, 48a-d and 49a-e by esterification, lactonization and reduction of the Ireland-Claisen rearranged products. Some of them were evaluated. It indicated that these deviratives prossess fruity and floral flavour.In part 2 of this thesis, we attempted to investigate the synthesis of quarternary carbon alcohols using [2,3]-Wittig rearrangement. By exploring [2,3]-Wittig reaction condition of some substrates, we found that [2,3]-Wittig rearrangement could be applied only to non-substituted allyl ethers 52 a and 56a. However, for substituted substrates 52b and 56b, negative results were obtained. Thus, more detailed work has to be done to demonstrate the scope and limitations.更多还原