論文中英文摘要格式

1、百度文庫(kù)- 讓每個(gè)人平等地提升自我附件 2作者姓名： 顧振華論文題目 ：2,3- 聯(lián)烯酸 ( 酰胺) 與聯(lián)烯和炔烴的偶聯(lián)環(huán)化反應(yīng)研究作者簡(jiǎn)介 ：顧振華，男，1979 年 02 月出生， 2002 年 09 月師從于中國(guó)科學(xué)院上海有機(jī)化學(xué)研究所麻生明教授，于2007 年 7 月獲博士學(xué)位。中文摘要聯(lián)烯是一類含有1,2-丙二烯官能團(tuán)的化合物。在聯(lián)烯的三個(gè)碳原子中，末端的兩個(gè)sp2雜化的碳原子以剩下的未雜化的 p 軌道與中間的 sp 雜化的碳原子的兩個(gè)互相垂直的 p- 軌道交蓋形成兩個(gè)互相垂直的 軌道。當(dāng)聯(lián)烯末端的同一碳原子上的取代基兩兩不同時(shí)， 聯(lián)烯則具有軸手性，其構(gòu)型可通過(guò) Cahn-Ingol

2、d-Prelog 規(guī)則判定。聯(lián)烯化合物獨(dú)特的反應(yīng)性一方面來(lái)自這種獨(dú)特的互相垂直交蓋 -軌道，另一方面來(lái)自聯(lián)烯末端的兩個(gè)碳原子（四個(gè)取代基）對(duì)不同取代基的裝載能力。通過(guò)對(duì)底物及反應(yīng)條件的調(diào)控，反應(yīng)可以選擇性的發(fā)生在聯(lián)烯的三個(gè)不同的碳原子上。 由于其獨(dú)特的結(jié)構(gòu)及反應(yīng)性， 聯(lián)烯在天然產(chǎn)物的合成中也有比較廣泛地應(yīng)用。近年來(lái)越來(lái)越多的含聯(lián)烯結(jié)構(gòu)的天然產(chǎn)物被分離和鑒定，到目前為止已有約150 個(gè)，這也極大地推動(dòng)了聯(lián)烯化學(xué)的發(fā)展。我們小組在官能化的聯(lián)烯的環(huán)化反應(yīng)方面也作了一些研究。最近我們小組發(fā)現(xiàn)并發(fā)展了官能化聯(lián)烯的雙分子氧化偶聯(lián)反應(yīng)，該反應(yīng)能有效的一步構(gòu)建雙環(huán)化合物?；谶@些發(fā)現(xiàn)，我的工作就是設(shè)計(jì)和發(fā)展聯(lián)

3、烯與聯(lián)烯、聯(lián)烯與炔烴的偶聯(lián)環(huán)化反應(yīng)。 主要包括以下三大部分：第一部分： 2,3-聯(lián)烯酸 (酰胺 )與聯(lián)烯的偶聯(lián)環(huán)化反應(yīng)1我們研究了 2,3-聯(lián)烯酸雙分子氧化偶聯(lián)反應(yīng)。 在研究過(guò)程中我們發(fā)展了三套氧化體系(a) n-C3H7I + O2, (b) KI + O 2, (c) 苯醌來(lái)實(shí)現(xiàn)鈀物種的催化循環(huán)， 并且還研究了在這三套氧化體系下的取代基效應(yīng)。2在實(shí)現(xiàn)了 2,3-聯(lián)烯酸自身雙分子氧化偶聯(lián)反應(yīng)之后我們又研究了2,3-聯(lián)烯酰胺與 1,2-聯(lián)烯基酮的交叉偶聯(lián)反應(yīng)。根據(jù)我們小組以前的研究2,3-聯(lián)烯酰胺有兩種環(huán)化方式：即氧進(jìn)攻生成 Furanimine 結(jié)構(gòu)的化合物，或氮進(jìn)攻生成內(nèi)酰胺的產(chǎn)物。通過(guò)X

4、- 射線單晶衍射和核磁研究，我們確認(rèn)了在這一雙分子氧化偶聯(lián)反應(yīng)中聯(lián)烯酰胺的關(guān)環(huán)方式是氧進(jìn)攻生成Furanimine 結(jié)構(gòu)的化合物，并且產(chǎn)物亞胺部分的結(jié)構(gòu)是順式的。同時(shí)我們還觀察到了2,3-聯(lián)烯酰胺自身雙分子偶聯(lián)環(huán)化后部分水解的產(chǎn)物。1百度文庫(kù)- 讓每個(gè)人平等地提升自我3我們發(fā)現(xiàn)了 2,3-聯(lián)烯酸與 2,3-聯(lián)烯醇的交叉偶聯(lián)反應(yīng)。 與前面的雙分子氧化偶聯(lián)環(huán)化反應(yīng)相比較，這是一種新的聯(lián)烯的雙分子偶聯(lián)反應(yīng)模式，即：(a) 該反應(yīng)并不需要添加任何氧化劑就實(shí)現(xiàn)了鈀物種的循環(huán)；(b) 只有 2,3-聯(lián)烯酸環(huán)化了，而2,3-聯(lián)烯醇則形成了一個(gè)開(kāi)鏈的1,3-共軛二烯結(jié)構(gòu)。 研究過(guò)程中我們發(fā)現(xiàn)當(dāng)使用二級(jí)醇時(shí)，我

5、們得到的是高選擇性的單一的反式產(chǎn)物， 該選擇性可以通過(guò)立體位阻作用及中間體-烯丙基鈀的- - 過(guò)程加以解釋。使用光學(xué)活性2,3-聯(lián)烯酸為底物，我們得到的是部分消旋的產(chǎn)物；但當(dāng)向體系中加入適量的質(zhì)子酸，如三氟醋酸時(shí)，產(chǎn)物的消旋能夠被很大程度的抑制。該實(shí)驗(yàn)間接證明了反應(yīng)的一個(gè)關(guān)鍵步驟- 羥基消除的一個(gè)中間體PdCl+OH - 的存在。我們對(duì)產(chǎn)物的衍生化也作了一些研究，如新形成的1,3-共軛二烯能夠順利地與缺電子親雙烯體發(fā)生Diels-Alder 反應(yīng)。4前面我們實(shí)現(xiàn)了不同官能化聯(lián)烯之間的偶聯(lián)反應(yīng)，但如何實(shí)現(xiàn)兩種性質(zhì)完全不同的聯(lián)烯之間的偶聯(lián)反應(yīng)是一個(gè)比較有挑戰(zhàn)性的課題。這里我們發(fā)展了官能化聯(lián)烯，如2

6、,3-聯(lián)烯酸與簡(jiǎn)單的聯(lián)烯的偶聯(lián)反應(yīng)。在該反應(yīng)中底物溴化鋰的溴負(fù)離子能夠有效的淬滅 -烯丙基鈀中間體，高選擇性地得到了 Z-式產(chǎn)物，而氯負(fù)離子或碘負(fù)離子并不能得到預(yù)期的烯丙基化合物。該反應(yīng)的高選擇性可能源于呋喃酮基鈀物種與簡(jiǎn)單聯(lián)烯靠近時(shí)的立體位阻作用。產(chǎn)物烯丙基溴衍生物在合成中是一個(gè)很有用的中間體，我們也進(jìn)行了對(duì)產(chǎn)物的衍生化研究，如它可以選擇性地與胺或苯亞磺酸鈉發(fā)生SN2型的親核取代反應(yīng)，與 CH3MgBr 在 CuBr?SMe2 催化下高選擇性地發(fā)生 SN2型的取代反應(yīng)，同時(shí)在 NaBH4 存在下 C-Br 鍵能被還原。第二部分： 2,3-聯(lián)烯酸與炔烴衍生物的偶聯(lián)環(huán)化反應(yīng)1我們發(fā)展了 2,3-

7、聯(lián)烯酸與炔丙醇碳酸酯的偶聯(lián)生成-聯(lián)烯基呋喃酮的反應(yīng)。 在反應(yīng)過(guò)程中新生成的聯(lián)烯基并沒(méi)有發(fā)生進(jìn)一步的轉(zhuǎn)化，有效的保留在了呋喃酮的-位。通過(guò)條件篩選我們確立了該反應(yīng)的最佳條件：即以醋酸鈀/三（ 2-呋喃基）膦為催化劑，二甲亞砜為溶劑。 研究過(guò)程中我們發(fā)現(xiàn)該反應(yīng)有明顯的取代基效應(yīng)，如 2,3-聯(lián)烯酸的-位和炔丙醇碳酸酯的炔烴末端同時(shí)為非氫取代時(shí)該反應(yīng)產(chǎn)率很低，這很可能是由于產(chǎn)物上 1,3-共軛二烯結(jié)構(gòu)上取代基的1,3-張力的影響。 我們同時(shí)對(duì)產(chǎn)物-聯(lián)烯基呋喃酮作了衍生化研究：(a) -聯(lián)烯基呋喃酮能與缺電子炔烴進(jìn)行 Diels-Alder 反應(yīng)，進(jìn)一步異構(gòu)化后能一步有效地構(gòu)建多取代及全取代苯環(huán)衍生物

8、，為這類化合物提供了一個(gè)有效的合成方法。(b) 我們還發(fā)現(xiàn) -聯(lián)烯基呋喃酮能發(fā)生高選擇性的羥碘化反應(yīng)，該反應(yīng)的選擇性可能2百度文庫(kù)- 讓每個(gè)人平等地提升自我來(lái)自親核試劑進(jìn)攻碘鎓三元環(huán)時(shí)的立體位阻效應(yīng)。這是少數(shù)幾例非雜原子導(dǎo)向的高選擇性羥碘化反應(yīng)。(c) 我們還初步研究了 -聯(lián)烯基呋喃酮的 -羥基化反應(yīng)。在有氧和堿性條件下， 2(5H)-呋喃酮能發(fā)生-羥基化反應(yīng)生成5-羥基 2(5H)-呋喃酮。當(dāng)?shù)孜锸?聯(lián)烯基呋喃酮時(shí)，-羥基化產(chǎn)物在 I2 存在下能有效的發(fā)生碘環(huán)化反應(yīng)，有效地構(gòu)建了雙環(huán)化合物。(d) 我們發(fā)現(xiàn)了 1,2,4(Z),7-四烯 ( -烯丙基 - -聯(lián)烯基呋喃酮 )異構(gòu)環(huán)化成八元環(huán)的

9、反應(yīng)。該反應(yīng)操作非常簡(jiǎn)單，只要將 1,2,4Z,7-四烯在二甲苯中 100 oC 攪拌反應(yīng) 6 小時(shí)即可，產(chǎn)率高達(dá) 98%。當(dāng)向體系中加入親雙烯體，如馬來(lái)酰胺時(shí)我們能得到一系列結(jié)構(gòu)新穎的橋環(huán)化合物， 反應(yīng)的立體選擇性是單一的， 即親雙烯體是以 endo方式從位阻較小的一面靠近底物的。我們對(duì)反應(yīng)的機(jī)理作了比較詳細(xì)的研究，當(dāng)將- 位烯丙基換成丙基取代基時(shí)，中間體發(fā)生了進(jìn)一步地1,7-氫遷移反應(yīng)，得到一種新的共軛三烯（順?lè)串悩?gòu)體）；當(dāng)將 -位烯丙基換成芐基取代基時(shí)，中間體則發(fā)生了進(jìn)一步的 6 - 電環(huán)化反應(yīng)，得到一類五元并六元的雙環(huán)化合物。氘代實(shí)驗(yàn)顯示聯(lián)烯末端的烷基上的氫與 -位烯丙基上的亞甲基的氫

10、有交換，這說(shuō)明了聯(lián)烯末端的烷基上的氫參與了該異構(gòu)化過(guò)程。最后我們認(rèn)為該反應(yīng)可能經(jīng)歷了如下一個(gè)比較復(fù)雜的過(guò)程：首先底物發(fā)生 1,5-H 遷移得到順?lè)磧蓚€(gè)中間體， 其中一個(gè)反式中間體可以通過(guò)8 -電環(huán)化最終形成八元環(huán)產(chǎn)物，而順式中間體則不能；但是這兩個(gè)中間體可以通過(guò)兩次1,7-H遷移相互轉(zhuǎn)化。2我們研究了2,3-聯(lián)烯酸與貧電子炔烴的偶聯(lián)反應(yīng)。當(dāng)炔烴是丙炔酸甲酯時(shí)，產(chǎn)物是1:1 加成和 1:2 加成的混合物，但新形成的C=C 雙鍵是單一反式的。通過(guò)條件優(yōu)化，我們能得到以 1:2 加成為主的產(chǎn)物，比例為9:116:1。我們還發(fā)現(xiàn) 2,3-聯(lián)烯酸與丙炔酸甲酯的 1:2 加成產(chǎn)物發(fā)生了-鍵的遷移，通過(guò)機(jī)理

11、研究我們認(rèn)為該-鍵的遷移可能是通過(guò)分子內(nèi)的兩次1,7-H 遷移來(lái)實(shí)現(xiàn)的。當(dāng)炔烴是炔酮時(shí)，并沒(méi)有發(fā)現(xiàn)1:2 加成的產(chǎn)物，但反應(yīng)得到的是一對(duì)順?lè)串悩?gòu)體。在n-Bu3P 作用下能有效地將順式產(chǎn)物轉(zhuǎn)化為反式產(chǎn)物，最終高選擇地得到以反式為主的產(chǎn)物。在這一部分的工作中我們發(fā)現(xiàn)以呋喃酮為母體的這一類結(jié)構(gòu)中較普遍地存在著的氫遷移反應(yīng)，而氫遷移得到的中間體（含兩個(gè)環(huán)外雙鍵的呋喃酮）并不穩(wěn)定，它會(huì)進(jìn)一步發(fā)生氫遷移或電環(huán)化反應(yīng)得到開(kāi)鏈或環(huán)狀的共軛烯烴衍生物。第三部分：鈀和胺共催化的有機(jī)碘化物與聯(lián)烯-醛的偶聯(lián)反應(yīng)有機(jī)小分子催化是近年來(lái)備受有機(jī)化學(xué)家關(guān)注的領(lǐng)域，如何結(jié)合有機(jī)小分子催3百度文庫(kù)- 讓每個(gè)人平等地提升自我化

12、劑及過(guò)渡金屬催化劑，在同一反應(yīng)中發(fā)揮它們各自不同的功能是一個(gè)十分有意義的課題。這里我們初步研究了過(guò)渡金屬鈀和有機(jī)小分子胺共催化的有機(jī)碘化物與聯(lián)烯-醛的偶聯(lián)反應(yīng)。在該反應(yīng)中聯(lián)烯的鈀碳化反應(yīng)得到 -烯丙基鈀中間體，其接受被胺活化了的醛的 -位的進(jìn)攻得到環(huán)狀化合物。通過(guò)條件篩選發(fā)現(xiàn)，二異丙胺和脯氨酸都能有效的催化該反應(yīng)，順?lè)幢葹?1:71:11。對(duì)比實(shí)驗(yàn)表明鈀和胺在該催化反應(yīng)中缺一不可。關(guān)鍵詞：聯(lián)烯、鈀、交叉偶聯(lián)、 1, n-氫遷移、電環(huán)化4百度文庫(kù)- 讓每個(gè)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-attack5百度文庫(kù)- 讓每個(gè)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、百度文庫(kù)- 讓每個(gè)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.7百度文庫(kù)- 讓每個(gè)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