论文中英文摘要格式

1、百度文库- 让每个人平等地提升自我附件 2作者姓名： 顾振华论文题目 ：2,3- 联烯酸 ( 酰胺) 与联烯和炔烃的偶联环化反应研究作者简介 ：顾振华，男，1979 年 02 月出生， 2002 年 09 月师从于中国科学院上海有机化学研究所麻生明教授，于2007 年 7 月获博士学位。中文摘要联烯是一类含有1,2-丙二烯官能团的化合物。在联烯的三个碳原子中，末端的两个sp2杂化的碳原子以剩下的未杂化的 p 轨道与中间的 sp 杂化的碳原子的两个互相垂直的 p- 轨道交盖形成两个互相垂直的 轨道。当联烯末端的同一碳原子上的取代基两两不同时， 联烯则具有轴手性，其构型可通过 Cahn-Ingol

2、d-Prelog 规则判定。联烯化合物独特的反应性一方面来自这种独特的互相垂直交盖 -轨道，另一方面来自联烯末端的两个碳原子（四个取代基）对不同取代基的装载能力。通过对底物及反应条件的调控，反应可以选择性的发生在联烯的三个不同的碳原子上。 由于其独特的结构及反应性， 联烯在天然产物的合成中也有比较广泛地应用。近年来越来越多的含联烯结构的天然产物被分离和鉴定，到目前为止已有约150 个，这也极大地推动了联烯化学的发展。我们小组在官能化的联烯的环化反应方面也作了一些研究。最近我们小组发现并发展了官能化联烯的双分子氧化偶联反应，该反应能有效的一步构建双环化合物。基于这些发现，我的工作就是设计和发展联

3、烯与联烯、联烯与炔烃的偶联环化反应。 主要包括以下三大部分：第一部分： 2,3-联烯酸 (酰胺 )与联烯的偶联环化反应1我们研究了 2,3-联烯酸双分子氧化偶联反应。 在研究过程中我们发展了三套氧化体系(a) n-C3H7I + O2, (b) KI + O 2, (c) 苯醌来实现钯物种的催化循环， 并且还研究了在这三套氧化体系下的取代基效应。2在实现了 2,3-联烯酸自身双分子氧化偶联反应之后我们又研究了2,3-联烯酰胺与 1,2-联烯基酮的交叉偶联反应。根据我们小组以前的研究2,3-联烯酰胺有两种环化方式：即氧进攻生成 Furanimine 结构的化合物，或氮进攻生成内酰胺的产物。通过X

4、- 射线单晶衍射和核磁研究，我们确认了在这一双分子氧化偶联反应中联烯酰胺的关环方式是氧进攻生成Furanimine 结构的化合物，并且产物亚胺部分的结构是顺式的。同时我们还观察到了2,3-联烯酰胺自身双分子偶联环化后部分水解的产物。1百度文库- 让每个人平等地提升自我3我们发现了 2,3-联烯酸与 2,3-联烯醇的交叉偶联反应。 与前面的双分子氧化偶联环化反应相比较，这是一种新的联烯的双分子偶联反应模式，即：(a) 该反应并不需要添加任何氧化剂就实现了钯物种的循环；(b) 只有 2,3-联烯酸环化了，而2,3-联烯醇则形成了一个开链的1,3-共轭二烯结构。 研究过程中我们发现当使用二级醇时，我

5、们得到的是高选择性的单一的反式产物， 该选择性可以通过立体位阻作用及中间体-烯丙基钯的- - 过程加以解释。使用光学活性2,3-联烯酸为底物，我们得到的是部分消旋的产物；但当向体系中加入适量的质子酸，如三氟醋酸时，产物的消旋能够被很大程度的抑制。该实验间接证明了反应的一个关键步骤- 羟基消除的一个中间体PdCl+OH - 的存在。我们对产物的衍生化也作了一些研究，如新形成的1,3-共轭二烯能够顺利地与缺电子亲双烯体发生Diels-Alder 反应。4前面我们实现了不同官能化联烯之间的偶联反应，但如何实现两种性质完全不同的联烯之间的偶联反应是一个比较有挑战性的课题。这里我们发展了官能化联烯，如2

6、,3-联烯酸与简单的联烯的偶联反应。在该反应中底物溴化锂的溴负离子能够有效的淬灭 -烯丙基钯中间体，高选择性地得到了 Z-式产物，而氯负离子或碘负离子并不能得到预期的烯丙基化合物。该反应的高选择性可能源于呋喃酮基钯物种与简单联烯靠近时的立体位阻作用。产物烯丙基溴衍生物在合成中是一个很有用的中间体，我们也进行了对产物的衍生化研究，如它可以选择性地与胺或苯亚磺酸钠发生SN2型的亲核取代反应，与 CH3MgBr 在 CuBr?SMe2 催化下高选择性地发生 SN2型的取代反应，同时在 NaBH4 存在下 C-Br 键能被还原。第二部分： 2,3-联烯酸与炔烃衍生物的偶联环化反应1我们发展了 2,3-

7、联烯酸与炔丙醇碳酸酯的偶联生成-联烯基呋喃酮的反应。 在反应过程中新生成的联烯基并没有发生进一步的转化，有效的保留在了呋喃酮的-位。通过条件筛选我们确立了该反应的最佳条件：即以醋酸钯/三（ 2-呋喃基）膦为催化剂，二甲亚砜为溶剂。 研究过程中我们发现该反应有明显的取代基效应，如 2,3-联烯酸的-位和炔丙醇碳酸酯的炔烃末端同时为非氢取代时该反应产率很低，这很可能是由于产物上 1,3-共轭二烯结构上取代基的1,3-张力的影响。 我们同时对产物-联烯基呋喃酮作了衍生化研究：(a) -联烯基呋喃酮能与缺电子炔烃进行 Diels-Alder 反应，进一步异构化后能一步有效地构建多取代及全取代苯环衍生物

8、，为这类化合物提供了一个有效的合成方法。(b) 我们还发现 -联烯基呋喃酮能发生高选择性的羟碘化反应，该反应的选择性可能2百度文库- 让每个人平等地提升自我来自亲核试剂进攻碘鎓三元环时的立体位阻效应。这是少数几例非杂原子导向的高选择性羟碘化反应。(c) 我们还初步研究了 -联烯基呋喃酮的 -羟基化反应。在有氧和碱性条件下， 2(5H)-呋喃酮能发生-羟基化反应生成5-羟基 2(5H)-呋喃酮。当底物是-联烯基呋喃酮时，-羟基化产物在 I2 存在下能有效的发生碘环化反应，有效地构建了双环化合物。(d) 我们发现了 1,2,4(Z),7-四烯 ( -烯丙基 - -联烯基呋喃酮 )异构环化成八元环的

9、反应。该反应操作非常简单，只要将 1,2,4Z,7-四烯在二甲苯中 100 oC 搅拌反应 6 小时即可，产率高达 98%。当向体系中加入亲双烯体，如马来酰胺时我们能得到一系列结构新颖的桥环化合物， 反应的立体选择性是单一的， 即亲双烯体是以 endo方式从位阻较小的一面靠近底物的。我们对反应的机理作了比较详细的研究，当将- 位烯丙基换成丙基取代基时，中间体发生了进一步地1,7-氢迁移反应，得到一种新的共轭三烯（顺反异构体）；当将 -位烯丙基换成苄基取代基时，中间体则发生了进一步的 6 - 电环化反应，得到一类五元并六元的双环化合物。氘代实验显示联烯末端的烷基上的氢与 -位烯丙基上的亚甲基的氢

10、有交换，这说明了联烯末端的烷基上的氢参与了该异构化过程。最后我们认为该反应可能经历了如下一个比较复杂的过程：首先底物发生 1,5-H 迁移得到顺反两个中间体， 其中一个反式中间体可以通过8 -电环化最终形成八元环产物，而顺式中间体则不能；但是这两个中间体可以通过两次1,7-H迁移相互转化。2我们研究了2,3-联烯酸与贫电子炔烃的偶联反应。当炔烃是丙炔酸甲酯时，产物是1:1 加成和 1:2 加成的混合物，但新形成的C=C 双键是单一反式的。通过条件优化，我们能得到以 1:2 加成为主的产物，比例为9:116:1。我们还发现 2,3-联烯酸与丙炔酸甲酯的 1:2 加成产物发生了-键的迁移，通过机理

11、研究我们认为该-键的迁移可能是通过分子内的两次1,7-H 迁移来实现的。当炔烃是炔酮时，并没有发现1:2 加成的产物，但反应得到的是一对顺反异构体。在n-Bu3P 作用下能有效地将顺式产物转化为反式产物，最终高选择地得到以反式为主的产物。在这一部分的工作中我们发现以呋喃酮为母体的这一类结构中较普遍地存在着的氢迁移反应，而氢迁移得到的中间体（含两个环外双键的呋喃酮）并不稳定，它会进一步发生氢迁移或电环化反应得到开链或环状的共轭烯烃衍生物。第三部分：钯和胺共催化的有机碘化物与联烯-醛的偶联反应有机小分子催化是近年来备受有机化学家关注的领域，如何结合有机小分子催3百度文库- 让每个人平等地提升自我化

12、剂及过渡金属催化剂，在同一反应中发挥它们各自不同的功能是一个十分有意义的课题。这里我们初步研究了过渡金属钯和有机小分子胺共催化的有机碘化物与联烯-醛的偶联反应。在该反应中联烯的钯碳化反应得到 -烯丙基钯中间体，其接受被胺活化了的醛的 -位的进攻得到环状化合物。通过条件筛选发现，二异丙胺和脯氨酸都能有效的催化该反应，顺反比为 1:71:11。对比实验表明钯和胺在该催化反应中缺一不可。关键词：联烯、钯、交叉偶联、 1, n-氢迁移、电环化4百度文库- 让每个人平等地提升自我The Coupling Cyclization Reaction Between 2,3-Allenoic Acids (o

13、r Amides)and Allene or AlkynesZhenhua GuABSTRACTAllenes are a class of compounds with a 1,2-diene functionality possessing two mutally perpendicular -orbitals. This type of molecules has chirality when the two subsituents on both of the two terminal carbons are different to each other. Their configu

14、ration can be assigned based on Cahn-Ingold-Prelog rule. The unique reactivity of allenes is due to the presence of the two perpendicular -orbitals as well as the substituent-loading capability. The reaction site may selectively be any carbon atom of the three-carbon unit via the tuning of the react

15、ion conditions and its substituents. In many cases, it is advantageous to use the allene unit as a retrosynthetic fragment. In addition, about 150 natural products containing an allenic or cumulenic structure are also known, which greatly stimulates the development of allene chemistry.The research p

16、rogram in our group is mainly on the cyclization of functionalized allenes. Recently, we have discovered an oxidative dimeric cyclization reaction of functionalized allenes, which would easily afford bicyclic compounds in one step. In this dissertation, I have focused on the design and development o

17、f the cross-coupling cyclization between two allenes, or allene and alkyne. Thus, the dissertation can be divided into three parts: Part I: The Coupling Cyclization Reaction between Two Allenes1. We have studied the oxidative dimeric cyclization of 2,3-allenoic acids. Three different sets of reactio

18、n conditions: (a) n-C3H7I + O2, (b) KI + O2, and (c) benzoquinone, have been developed to regenerate the catalytic active Pd(II) species. We also studied the substituent effects of the oxidative dimeric cyclization reaction under these three systems.2. We realized the heterodimerization reaction of

19、2,3-allenamides and 1,2-allenyl ketones. Based on the previous study on the coupling-cyclization reaction of 2,3-allenamides with organic halides in this group, there are two cyclization patterns: one is the N-attack to form -lactams and the other is theO-attack to form furanimines. The NMR and X-ra

20、y diffraction studies show that the reaction only afforded furanimine-type structures, the O-attack5百度文库- 让每个人平等地提升自我products. We also observed the formation of the homodimerization monohydrolysis product of 2,3-allenamides, whose structure was also determined by the X-ray diffraction analysis.3.We

21、discovered and studied the cyclizationof2,3-allenoic acids inthe presence of2,3-allenols. It is a new reaction pattern between two different type of functionalized allenes, in which (1) the catalytically active Pd(II) species would be regenerated “automatically”after the reaction and (2) two allenes

22、 function differently, ., 2,3-allenoic acids form the butenolide skeletons while the 2,3-allenols introduce the 1,3-diene substituent to the-position of the butenolides formed. It is interesting when secondary alcohols were usedthe reaction afforded exclusively the E-products, which might be explain

23、ed via a - - process of the -allylic palladium intermediate. When optically active 2,3-allenoic acid was used as a substrate, the reaction afforded the product with partial racemization. Interestingly,the addition of an carboxylic acid, ., trifluoroacetic acid, could greatly inhibit the racemization

24、 of the products, which indirectly supported the formation of PdCl+OH -during the -hydroxide elimination process. We also studied the Diels-Alder reaction of the products with dienophiles.4. We have developed a cyclization reaction of 2,3-allenoic acids in the presence of simple allenes. The allenes

25、 used in the above three cyclization reactions are all functionalized ones. It is a challenge to couple with two allenes with completely different nature, such as 2,3-allenoic acids and simple allenes. In the presence of LiBr, we successfully realized the coupling-cylization between 2,3-allenoic aci

26、ds and simple allenes affording highly selectively gave the Z-isomer. A plausible mechanism based on face-selective coordination of allenes was proposed to explain this Z-selectivity. The newly formed allylic bromide derivatives are useful synthetic intermediates, which could be further elaborated v

27、ia the SN2 nucleophilic substitution with amine or sodium benzenesulfinate, the reduction of C-Br bond by NaBH4 and the CuBr?SMe2-catalyzed SN2-substitution with CH 3MgBr.Part II: The Coupling Cyclization Reactions Between 2,3-Allenoic Acids and Alkynes1.We have established a protocol of the palladi

28、um-catalyzed coupling reaction of 2,3-allenoic acids with propargylic carbonates forming -allenyl butenolides, in which the newly formed allene moiety does not undergo further transformation under the current coupling cyclization conditions. A survey of ligands showed that tri-(2-furyl)phosphine is6

29、百度文库- 让每个人平等地提升自我the best for this reaction. It was observed there are serious substituent effects, ., thereaction of2,3-allenoicacids withnon-hydrogen substituents of-positionwithnon-terminal propargylic carbonates would give the preducts in very poor yields probablydue to the high 1,3-strain of th

30、e products. We also studied the synthetic application ofthese -allenyl butenolides:(a) It is a challenge to synthesize poly- and fully- substituted benzene derivatives. The-allenyl butenolides would highly selectively react with electron-deficient alkynes to givepoly- and fully- substituted benzene

31、derivatives.(b) We studied the highlyregio- and stereoselective iodohydroxylationof-allenylbutenolides. Electrophilicadditions of allenes are synthetically attractive since twofunctionalities are introduced in one step. However, the poor regio- and stereoselectivitygreatly inhibit the application of

32、 this reaction. It is interesting to observed that the-allenylbutenolideswouldhighselectivelyafford4-3-hydroxy-2 -iodoalk-1(Z)enyl-2(5 H)-furanones in the presence of I2 and H 2O. The regio- and stereoselectivity of this reaction may be controlled by the electronic and steric effects of the furanone

33、 ring.(c)We studied the -hydroxylation reaction of-allenyl butenolides. The -hydroxylationproducts could be easily cyclized in the presence of2 .I(d) Wehavediscoveredacycloisomerizationreactionof1,2,4(Z),7-tetraenes, .-allyl-allenyl butenolides, for the synthesis of eight-membered bicyclic compounds

34、.The procedures are straightforward, the conditions (xylene, 100oC, 6 h) are mild, and the yields are high (up to 98% yield). In the presence of dienophile, ., 1 H-pyrrole-2,5-dione, the reaction would highly selectively afford poly-cyclic products. When a propyl group was induced to -position inste

35、ad of the alllylic one, the reaction would give a new triene. When a benzyl group was induced to -position, the intermediate would afford a newsix-membered ring via 6 -electrocyclization. The deuterium-labeling studies show that the hydrogen of the alkyl group at allenyl terminal involved in the iso

36、merization process. We proposed that 1,5-H shift of the starting material would afford both E- and Z-intermediates. The E-intermediates would afford the eight-membered ring compounds via 8 -electrocyclization, while the Z-isomer could not. However, these two intermediates could be interconverted to

37、each other via a double 1,7-H shift.7百度文库- 让每个人平等地提升自我2. We have studied the coupling cyclization reaction of 2,3-allenoic acids in the presence of electron-deficient alkynes. When methyl propiolate was used as substrate, the newly formed C=C double bond in the products was exclusively in their E-fo

38、rms. However, both 1:1 and 1:2 adducts were formed. After optimizing the reaction condition, 1:2 adducts were formed as the major products with the ratio up to 16:1. It is interesting that “-bond migration”was observed in the 1:2 adducts. After some mechanistic studies we believed that the “-bond migration ”product may be formed via double 1,7-H shifts of the normal 1:2 adducts. When 1-a