论文中英文摘要格式附件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π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-Ingold-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π-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 + O2, (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-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。

(a)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。

(b)我们还初步研究了β-联烯基呋喃酮的γ-羟基化反应。

在有氧和碱性条件下，2(5H)-呋喃酮能发生γ-羟基化反应生成5-羟基2(5H)-呋喃酮。

当底物是β-联烯基呋喃酮时，γ-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。

(c)我们发现了1,2,4(Z),7-四烯(α-烯丙基-β-联烯基呋喃酮)异构环化成八元环的反应。

该反应操作非常简单，只要将1,2,4Z,7-四烯在二甲苯中100 o C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α-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α-位烯丙基换成苄基取代基时，中间体则发生了进一步的6π-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α-位烯丙基上的亚甲基的氢有交换，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8π-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。

1．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9:1~16:1。

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π-键的迁移，通过机理研究我们认为该π-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化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π-烯丙基钯中间体，其接受被胺活化了的醛的α-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1:7~1:11。

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The Coupling Cyclization Reaction Between 2,3-Allenoic Acids (orAmides) and Allene or AlkynesZhenhua GuABSTRACTAllenes are a class of compounds with a 1,2-diene functionality possessing two mutally perpendicular π-orbitals. This type of molecules has chirality when the two subsituents on both of the two terminal carbons are different to each other. Their configuration can be assigned based on Cahn-Ingold-Prelog rule. The unique reactivity of allenes is due to the presence of the two perpendicular π-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 reaction 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 program 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 of 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 differentsets of reaction 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 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 theN-attack to form γ-lactams and the other is the O-attack to form furanimines. The NMR and X-ray diffraction studies show that the reaction only afforded furanimine-type structures, the O-attack 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 discovered and studied the cyclization of 2,3-allenoic acids in the 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 function differently, i.e., 2,3-allenoic acids form the butenolide skeletons while the 2,3-allenols introduce the 1,3-diene substituent to the β-position of the butenolides formed. It is interesting when secondary alcohols were used the reaction afforded exclusively the E-products, which might be explained via a σ-π-σ process of the π-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, i.e., trifluoroacetic acid, could greatly inhibit the racemization of the products, which indirectly supported the formation of [PdCl+][OH-] during the β-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 simpleallenes. The allenes 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 acids 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 via the S N2 nucleophilic substitution with amine or sodium benzenesulfinate, the reduction of C-Br bond by NaBH4 and the CuBr•SMe2-catalyzed S N2’-substitution with CH3MgBr.Part II: The Coupling Cyclization Reactions Between 2,3-Allenoic Acids and Alkynes1.We have established a protocol of the palladium-catalyzed coupling reaction of2,3-allenoic acids with propargylic carbonates forming β-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 is the best for this reaction. It was observed there are serious substituent effects, i.e., the reaction of 2,3-allenoic acids with non-hydrogen substituents of α-position with non-terminal propargylic carbonates would give the preducts in very poor yields probably due to the high 1,3-strain of the products. We also studied the synthetic application of these β-allenyl butenolides:(a)It is a challenge to synthesize poly- and fully- substituted benzene derivatives. Theβ-allenyl butenolides would highly selectively react with electron-deficient alkynes to give poly- and fully- substituted benzene derivatives.(b)We studied the highly regio- and stereoselective iodohydroxylation of β-allenylbutenolides. Electrophilic additions of allenes are synthetically attractive since two functionalities are introduced in one step. However, the poor regio- and stereoselectivity greatly inhibit the application of this reaction. It is interesting to observed that the β-allenyl butenolides would high selectively afford 4-[3’-hydroxy-2’-iodoalk-1’(Z)enyl]-2(5H)-furanones in the presence of I2and H2O.The regio- and stereoselectivity of this reaction may be controlled by the electronic and steric effects of the furanone ring.(c)We studied the γ-hydroxylation reaction of β-allenyl butenolides. Theγ-hydroxylation products could be easily cyclized in the presence of I2.(d)We have discovered a cycloisomerization reaction of 1,2,4(Z),7-tetraenes, i.e.α-allyl-β-allenyl butenolides, for the synthesis of eight-membered bicyclic compounds. The procedures are straightforward, the conditions (xylene, 100 o C, 6 h) are mild, and the yields are high (up to 98% yield). In the presence of dienophile, i.e., 1H-pyrrole-2,5-dione, the reaction would highly selectively afford poly-cyclic products. When a propyl group was induced to α-position instead of the alllylic one, the reaction would give a new triene. When a benzyl group was induced to α-position, the intermediate would afford a new six-membered ring via 6π-electrocyclization. The deuterium-labeling studies show that the hydrogen of thealkyl group at allenyl terminal involved in the isomerization process. We proposedthat 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 via8π-electrocyclization, while the Z-isomer could not. However, these two intermediatescould be interconverted to each other via a double 1,7-H shift.2.We have studied the coupling cyclization reaction of 2,3-allenoic acids in the presenceof electron-deficient alkynes. When methyl propiolate was used as substrate, thenewly formed C=C double bond in the products was exclusively in their E-forms.However, both 1:1 and 1:2 adducts were formed. After optimizing the reactioncondition, 1:2 adducts were formed as the major products with the ratio up to 16:1.It is interesting that “π-bond migration” was observed in the 1:2 adducts. After somemechanistic studies we believed that the “π-bond migration” product may be formedvia double 1,7-H shifts of the normal 1:2 adducts. When 1-alkynyl ketones were usedas substrates, no 1:2 adduct was observed. Instead, the reaction afforded a mixture ofZ/E isomers of the 1:1 adduct. In the presence of a catalytic n-Bu3P, the Z/E mixtureswould highly selectively be converted to the E-isomers.Part III: The Cross-Coupling Reaction between Allene-Aldehyde and Organic Halides under the Cocatalysis of Pd(OAc)2/TFP and the Secondary AminesRecently, the use of organic molecule as catalyst has attracted muchattention of organic chemists. It is a challenge to develop a reactionco-catalyzed by transition metal and organic molecule, in which two catalystsfunctioned differently. In this part, we have studied the cross-couplingreaction of allene-aldehydes with organic halides under the cocatalysis ofPd(OAc)2/TFP and the secondary amines. The π-allylic palladiumintermediate could be trapped by the nucleophlic attack of α-carbon ofaldehyde, which was activated by the secondary amine. After some survey, wefound two sets of conditions: Pd(OAc)2/TFP/diisopropylamine andPd(OAc)2/TFP/proline/K2CO3. The ratio of cis/trans is 1:7~1:11. The reactionwould not take place in the absence of either the palladium complex or anamine.Key words: allene •palladium •cross-coupling •1,n-hydrogen shift •electrocyclization11。