有機合成中間體概念綜合教學(xué)實驗

有機合成中間體概念綜合教學(xué)實驗——以烯基硅的高效合成與衍生化應(yīng)用為例摘要：有機合成中間體是一個歷史悠久，應(yīng)用廣泛的概念，在有機合成大師、諾貝爾獎獲得者EliasJamesCorey提出了逆合成分析概念后，與合成子概念息息相關(guān)的有機合成中間體進一步發(fā)揮著中流砥柱的作用。烯基硅化合物由于其多功能反應(yīng)性、低毒、穩(wěn)定等特點在近年來備受矚目，合成與應(yīng)用方法層出不窮，成為了一個新興的有機合成中間體。本實驗項目將基于烯基硅中間體，把有機合成中間體概念引入到有機化學(xué)實驗教學(xué)中。以制備與應(yīng)用兩個模塊化實驗內(nèi)容為主體，改變了原先教學(xué)實驗較為單一且缺乏故事性、目的性、理論性的特點，同時涉及經(jīng)典人名反應(yīng)Hiyama偶聯(lián)及最新科研成果，覆蓋了大量有機合成方法學(xué)研究和實驗的基本操作、并通過探究性實驗激發(fā)學(xué)生學(xué)習(xí)興趣。本實驗由模塊化實驗組成，允許高校較為容易地依照自身條件改編選用入課程教學(xué)中。關(guān)鍵詞：有機合成中間體；逆合成分析；合成子；烯基硅化合物；Hiyama偶聯(lián)ATeachingExperimentabouttheConceptofOrganicIntermediate——TakingtheEfficientSynthesisandApplicationofVinylsilanesasanExampleAbstract:Organicintermediateisalong-establishedandwidelyusedconcept,afterEliasJamesCorey,theorganicsynthesismasterandNobelprizewinnerdevelopedtheconceptofinversesynthesis,organicintermediates,whicharecloselyrelatedtotheconceptofsynthonhavefurtherplayedadominantroleinorganicsynthesis.Vinylsilaneshaveattractedmuchattentioninrecentyearsduetotheirversatilereactivity,lowtoxicity,highstability,lotsofsynthesisandapplicationmethodshavebeendevelopedwhichmakevinylsilanesapromisingorganicintermediates.Herein，weintroducetheconceptoforganicintermediatetotheteachingexperimentbasedonvinylsilaneintermediates.Basedonthepreparationandapplicationoftwomodularexperiments,weimprovetheshortcomingsofclassicteachingexperimentslikesimplicityandthelackofstory、goalandtheoreticalproperty.Besides,thisexperimentisrelatedtoclassicnamereaction,Hiyamacrosscouplingandtheresearchfrontline,coveredabundantbasicoperationsaboutorganicsynthesismethodologyresearchandteachingexperimental、Exploratoryexperiment,whichcaninspirestudent’sinterestinlearning.Thecharacterofmodularexperimentallowseachcollegesadaptandselectthisschemeintoteachingplanbasedontheirownconditionseasily.KeyWords:Organicsynthesisintermediate;inversesynthesis;synthon;vinylsilanes;Hiyamacrosscoupling1引言有機化學(xué)自1828年德國化學(xué)家魏勒（E.Wohler）借助無機化合物制備尿素發(fā)軔以來，已經(jīng)與人類的生活息息相關(guān)，密不可分。在有機化學(xué)的產(chǎn)學(xué)研過程中，為獲取所需要的有機化合物，人們常常要通過商業(yè)購買，或經(jīng)由商業(yè)可得的原料自行合成?；谶@樣的需求，越來越多的化合物經(jīng)由人們的研究和生產(chǎn)，成為了商業(yè)可得的有機合成原料，即有機合成中間體。圖SEQ圖\*ARABIC1：逆合成分析法在過去的幾十年中，針對有機合成中間體的研究不斷進行，遠遠超過了1951年數(shù)千的可得數(shù)量。ADDINEN.CITE<EndNote><Cite><Author>Allen</Author><Year>1951</Year><RecNum>7</RecNum><DisplayText><styleface="superscript">1</style></DisplayText><record><rec-number>7</rec-number><foreign-keys><keyapp="EN"db-id="tzzrza5fc2xpate0rd65rvvlszrtp2a5d5pe"timestamp="1586949872">7</key></foreign-keys><ref-typename="Book">6</ref-type><contributors><authors><author>SHIRLEYDavidAllen</author></authors></contributors><titles><title>PreparationofOrganicIntermediates</title></titles><dates><year>1951</year></dates><publisher>JohnWiley&Sons</publisher><urls></urls></record></Cite></EndNote>1逆合成分析法（圖1）大大促進有機合成進步的同時，也加速了有機合成中間體的選擇與開發(fā)——通過逆合成手段，我們通過不同切斷邏輯獲取合成子，并提供有機合成中間體來擔(dān)當(dāng)合成子等價試劑來實現(xiàn)逆合成分析與有機合成ADDINEN.CITE<EndNote><Cite><Author>Warren</Author><Year>2010</Year><RecNum>8</RecNum><DisplayText><styleface="superscript">2</style></DisplayText><record><rec-number>8</rec-number><foreign-keys><keyapp="EN"db-id="tzzrza5fc2xpate0rd65rvvlszrtp2a5d5pe"timestamp="1586951836">8</key></foreign-keys><ref-typename="Book">6</ref-type><contributors><authors><author>StuartWarren</author><author>PaulWyatt</author></authors></contributors><titles><title><styleface="normal"font="default"charset="134"size="100%">有機合成：切斷法（原書第</style><styleface="normal"font="default"size="100%">2</style><styleface="normal"font="default"charset="134"size="100%">版）</style><styleface="normal"font="default"size="100%">[OrganicSynthesis:TheDisconnectionApproach]</style></title></titles><dates><year>2010</year></dates><publisher><styleface="normal"font="default"charset="134"size="100%">科學(xué)出版社</style></publisher><isbn>9787030276704</isbn><urls></urls></record></Cite></EndNote>2。有機合成與有機合成中間體兩個概念已然密不可分（圖2）。通過教學(xué)實驗掌握中間體構(gòu)建、應(yīng)用的知識點，將有利于化學(xué)、藥學(xué)等專業(yè)專業(yè)素質(zhì)的培養(yǎng)。圖SEQ圖\*ARABIC1：逆合成分析法圖SEQ圖\*ARABIC2:有機合成與有機合成中間體：a)格氏試劑的親核反應(yīng)ADDINEN.CITE<EndNote><Cite><Author>Haugan</Author><Year>1997</Year><RecNum>10</RecNum><DisplayText><styleface="superscript">3</style></DisplayText><record><rec-number>10</rec-number><foreign-keys><keyapp="EN"db-id="tzzrza5fc2xpate0rd65rvvlszrtp2a5d5pe"timestamp="1586963375">10</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Haugan,JarleAndré</author><author>Songe,P?l</author><author>R?mming,Christian</author><author>Rise,Frode</author><author>Hartshorn,MichaelP.</author><author>Merchán,Manuela</author><author>Robinson,WardT.</author><author>Roos,Bj?rnO.</author><author>Vallance,Claire</author><author>Wood,BryanR.</author></authors></contributors><titles><title>TotalSynthesisofC31-MethylKetoneApocarotenoids2:TheFirstTotalSynthesisof(3R)-Triophaxanthin</title><secondary-title>ActaChemicaScandinavica</secondary-title></titles><periodical><full-title>ActaChemicaScandinavica</full-title></periodical><pages>1096-1103</pages><volume>51</volume><section>1096</section><dates><year>1997</year></dates><isbn>0904-213X</isbn><urls></urls><electronic-resource-num>10.3891/acta.chem.scand.51-1096</electronic-resource-num></record></Cite></EndNote>3b)鎂鹵交換ADDINEN.CITE<EndNote><Cite><Author>Knochel</Author><Year>2003</Year><RecNum>11</RecNum><DisplayText><styleface="superscript">4</style></DisplayText><record><rec-number>11</rec-number><foreign-keys><keyapp="EN"db-id="tzzrza5fc2xpate0rd65rvvlszrtp2a5d5pe"timestamp="1586963651">11</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Knochel,P.</author><author>Dohle,W.</author><author>Gommermann,N.</author><author>Kneisel,F.F.</author><author>Kopp,F.</author><author>Korn,T.</author><author>Sapountzis,I.</author><author>Vu,V.A.</author></authors></contributors><auth-address>DepartmentChemie,Ludwig-Maximilians-UniversitatMunchen,Butenandtstrasse5-13,HausF,81377Munich,Germany.paul.knochel@cup.uni-muenchen.de</auth-address><titles><title>Highlyfunctionalizedorganomagnesiumreagentspreparedthroughhalogen-metalexchange</title><secondary-title>AngewChemIntEdEngl</secondary-title></titles><periodical><full-title>AngewChemIntEdEngl</full-title></periodical><pages>4302-20</pages><volume>42</volume><number>36</number><edition>2003/09/23</edition><dates><year>2003</year><pub-dates><date>Sep22</date></pub-dates></dates><isbn>1433-7851(Print) 1433-7851(Linking)</isbn><accession-num>14502700</accession-num><urls><related-urls><url>/pubmed/14502700</url></related-urls></urls><electronic-resource-num>10.1002/anie.200300579</electronic-resource-num></record></Cite></EndNote>4c)環(huán)氧開環(huán)ADDINEN.CITE<EndNote><Cite><Author>Ashcroft</Author><Year>1984</Year><RecNum>12</RecNum><DisplayText><styleface="superscript">5</style></DisplayText><record><rec-number>12</rec-number><foreign-keys><keyapp="EN"db-id="tzzrza5fc2xpate0rd65rvvlszrtp2a5d5pe"timestamp="1586964274">12</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Ashcroft,MartynR.</author><author>Bougeard,Peter</author><author>Bury,Adrian</author><author>Cooksey,ChristopherJ.</author><author>Johnson,MichaelD.</author><author>Hungerford,JamesM.</author><author>Lampman,GaryM.</author></authors></contributors><titles><title>Homolyticdisplacementatsaturatedcarbon.Part9.Thereactionsoftrichloromethanesulfonylchloridewithpent-4-enylcobaloximesandwitholefins.Anovelrouteto(trichloroethyl)sulfolanesviaanSHimechanism</title><secondary-title>TheJournalofOrganicChemistry</secondary-title></titles><periodical><full-title>TheJournalofOrganicChemistry</full-title></periodical><pages>1751-1761</pages><volume>49</volume><number>10</number><section>1751</section><dates><year>1984</year></dates><isbn>0022-3263 1520-6904</isbn><urls></urls><electronic-resource-num>10.1021/jo00184a017</electronic-resource-num></record></Cite></EndNote>5d)制備酚醛樹脂ADDINEN.CITE<EndNote><Cite><Author>Sunitha</Author><Year>2017</Year><RecNum>13</RecNum><DisplayText><styleface="superscript">6</style></DisplayText><record><rec-number>13</rec-number><foreign-keys><keyapp="EN"db-id="tzzrza5fc2xpate0rd65rvvlszrtp2a5d5pe"timestamp="1586964449">13</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Sunitha,K.</author><author>Bhuvaneswari,S.</author><author>Mathew,Dona</author><author>Unnikrishnan,G.</author><author>Nair,C.P.Reghunadhan</author></authors></contributors><titles><title>CombPolymerNetworkofPolydimethylsiloxanewithaNovolacStem:SynthesisviaClickCouplingandSurfaceMorphologyArchitecturingbySolvents</title><secondary-title>Macromolecules</secondary-title></titles><periodical><full-title>Macromolecules</full-title></periodical><pages>9656-9665</pages><volume>50</volume><number>24</number><section>9656</section><dates><year>2017</year></dates><isbn>0024-9297 1520-5835</isbn><urls></urls><electronic-resource-num>10.1021/acs.macromol.7b02046</electronic-resource-num></record></Cite></EndNote>6e)制備苦味酸ADDINEN.CITE<EndNote><Cite><Author>Crampton</Author><Year>2002</Year><RecNum>14</RecNum><DisplayText><styleface="superscript">7</style></DisplayText><record><rec-number>14</rec-number><foreign-keys><keyapp="EN"db-id="tzzrza5fc2xpate0rd65rvvlszrtp2a5d5pe"timestamp="1586964572">14</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Crampton,MichaelR.</author><author>Cropper,EmmaL.</author><author>Gibbons,LindaM.</author><author>Millar,RossW.</author></authors></contributors><titles><title>Thenitrationofarenesinperfluorocarbonsolvents</title><secondary-title>GreenChemistry</secondary-title></titles><periodical><full-title>GreenChemistry</full-title></periodical><pages>275-278</pages><volume>4</volume><number>3</number><section>275</section><dates><year>2002</year></dates><isbn>14639262 14639270</isbn><urls></urls><electronic-resource-num>10.1039/b200627h</electronic-resource-num></record></Cite></EndNote>7f)制備三溴苯酚ADDINEN.CITE<EndNote><Cite><Author>Sun</Author><Year>2019</Year><RecNum>15</RecNum><DisplayText><styleface="superscript">8</style></DisplayText><record><rec-number>15</rec-number><foreign-keys><keyapp="EN"db-id="tzzrza5fc2xpate0rd65rvvlszrtp2a5d5pe"timestamp="1586964662">15</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Sun,Meng</author><author>Zhang,Shaowei</author><author>Zhang,Jie</author><author>Xia,Wen</author><author>Chen,Jialiang</author><author>Yu,Xianyong</author></authors></contributors><titles><title>Crystalstructureandcatalyticpropertiesofavanadiumcomplexcis-[VO2(Him-py)(im-py)]2·3H2O</title><secondary-title>JournalofCoordinationChemistry</secondary-title></titles><periodical><full-title>JournalofCoordinationChemistry</full-title></periodical><pages>1899-1909</pages><volume>72</volume><number>11</number><section>1899</section><dates><year>2019</year></dates><isbn>0095-8972 1029-0389</isbn><urls></urls><electronic-resource-num>10.1080/00958972.2019.1618848</electronic-resource-num></record></Cite></EndNote>8g)雙鍵異構(gòu)化ADDINEN.CITE<EndNote><Cite><Author>Fa?bender</Author><Year>2019</Year><RecNum>3</RecNum><DisplayText><styleface="superscript">9</style></DisplayText><record><rec-number>3</rec-number><foreign-keys><keyapp="EN"db-id="tzzrza5fc2xpate0rd65rvvlszrtp2a5d5pe"timestamp="1586930376">3</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Fa?bender,SvenjaI.</author><author>Molloy,JohnJ.</author><author>Mück‐Lichtenfeld,Christian</author><author>Gilmour,Ryan</author></authors></contributors><titles><title>GeometricE→ZIsomerisationofAlkenylSilanesbySelectiveEnergyTransferCatalysis:StereodivergentSynthesisofTriarylethylenesviaaFormalanti‐Metallometallation</title><secondary-title>AngewandteChemie</secondary-title></titles><periodical><full-title>AngewandteChemie</full-title></periodical><pages>18792-18799</pages><volume>131</volume><number>51</number><section>18792</section><dates><year>2019</year></dates><isbn>0044-8249 1521-3757</isbn><urls></urls><electronic-resource-num>10.1002/ange.201910169</electronic-resource-num></record></Cite></EndNote>9h)硅醇轉(zhuǎn)換ADDINEN.CITE<EndNote><Cite><Author>Denmark</Author><Year>2006</Year><RecNum>2</RecNum><DisplayText><styleface="superscript">10</style></DisplayText><record><rec-number>2</rec-number><foreign-keys><keyapp="EN"db-id="tzzrza5fc2xpate0rd65rvvlszrtp2a5d5pe"timestamp="1586930361">2</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Denmark,S.E.</author><author>Neuville,L.</author><author>Christy,M.E.</author><author>Tymonko,S.A.</author></authors></contributors><auth-address>RogerAdamsLaboratory,DepartmentofChemistry,UniversityofIllinois,Urbana,Illinois61801,USA.denmark@</auth-address><titles><title>Aqualitativeexaminationoftheeffectsofsiliconsubstituentsontheefficiencyofcross-couplingreactions</title><secondary-title>JOrgChem</secondary-title></titles><periodical><full-title>JOrgChem</full-title></periodical><pages>8500-9</pages><volume>71</volume><number>22</number><edition>2006/10/27</edition><keywords><keyword>Alkenes/*chemistry</keyword><keyword>MolecularStructure</keyword><keyword>OrganosiliconCompounds/*chemicalsynthesis/*chemistry</keyword><keyword>Silanes/*chemistry</keyword></keywords><dates><year>2006</year><pub-dates><date>Oct27</date></pub-dates></dates><isbn>0022-3263(Print) 0022-3263(Linking)</isbn><accession-num>17064026</accession-num><urls><related-urls><url>/pubmed/17064026</url></related-urls></urls><electronic-resource-num>10.1021/jo061481t</electronic-resource-num></record></Cite></EndNote>10i)Hiyama偶聯(lián)ADDINEN.CITE<EndNote><Cite><Author>Du</Author><Year>2017</Year><RecNum>1</RecNum><DisplayText><styleface="superscript">11</style></DisplayText><record><rec-number>1</rec-number><foreign-keys><keyapp="EN"db-id="tzzrza5fc2xpate0rd65rvvlszrtp2a5d5pe"timestamp="1586930297">1</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Du,Xiaoyong</author><author>Hou,Wenjun</author><author>Zhang,Yanlu</author><author>Huang,Zheng</author></authors></contributors><titles><title>Pincercobaltcomplex-catalyzedZ-selectivehydrosilylationofterminalalkynes</title><secondary-title>OrganicChemistryFrontiers</secondary-title></titles><periodical><full-title>OrganicChemistryFrontiers</full-title></periodical><pages>1517-1521</pages><volume>4</volume><number>8</number><section>1517</section><dates><year>2017</year></dates><isbn>2052-4129</isbn><urls></urls><electronic-resource-num>10.1039/c7qo00250e</electronic-resource-num></record></Cite></EndNote>112010年諾貝爾化學(xué)獎授予Heck,Negishi和Suzuki，表彰他們在交叉偶聯(lián)反應(yīng)方面做出的杰出貢獻。偶聯(lián)反應(yīng)對于現(xiàn)代合成化學(xué)、醫(yī)藥領(lǐng)域和活性生物分子的合成至關(guān)重要，人們利用偶聯(lián)反應(yīng)高效地合成了各種復(fù)雜的分子，而偶聯(lián)反應(yīng)離不開三種元素——硼、硅和錫。ADDINEN.CITE<EndNote><Cite><Author>Chen</Author><Year>2018</Year><RecNum>18</RecNum><DisplayText><styleface="superscript">12</style></DisplayText><record><rec-number>18</rec-number><foreign-keys><keyapp="EN"db-id="tzzrza5fc2xpate0rd65rvvlszrtp2a5d5pe"timestamp="1586966074">18</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Chen,Jianhui</author><author>Xi,Tuo</author><author>Lu,Zhan</author></authors></contributors><titles><title>10gram-scalesynthesisofachiraloxazolineiminopyridineligandanditsapplications</title><secondary-title>OrganicChemistryFrontiers</secondary-title></titles><periodical><full-title>OrganicChemistryFrontiers</full-title></periodical><pages>247-253</pages><volume>5</volume><number>2</number><section>247</section><dates><year>2018</year></dates><isbn>2052-4129</isbn><urls></urls><electronic-resource-num>10.1039/c7qo00816c</electronic-resource-num></record></Cite></EndNote>16其中，有機硅材料在生產(chǎn)生活中應(yīng)用廣泛，例如線性聚硅氧烷產(chǎn)品——硅油是常見的潤滑劑、添加劑和油浴的熱載體。有機硅中間體同樣也是有機合成的重要合成砌塊，正是由于其較好的穩(wěn)定性和多種的轉(zhuǎn)化途徑，它可以為之后進行精準構(gòu)筑碳碳鍵或碳氧鍵以及修飾硅原子上的基團提供便利。但是在本科理論教學(xué)和實驗教學(xué)中缺少對有機硅化學(xué)的講解，存在一定空白與填補空間。基于以上教學(xué)目標(biāo)，我們所設(shè)計的教學(xué)實驗，將圍繞逆合成分析法所緊密結(jié)合的有機合成中間體概念進行。以新興有機硅中間體——烯基硅中間體的高效合成與衍生化應(yīng)用為例，選擇了合成方法學(xué)領(lǐng)域發(fā)表的較新科研成果ADDINEN.CITE<EndNote><Cite><Author>Chen</Author><Year>2018</Year><RecNum>18</RecNum><DisplayText><styleface="superscript">12</style></DisplayText><record><rec-number>18</rec-number><foreign-keys><keyapp="EN"db-id="tzzrza5fc2xpate0rd65rvvlszrtp2a5d5pe"timestamp="1586966074">18</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Chen,Jianhui</author><author>Xi,Tuo</author><author>Lu,Zhan</author></authors></contributors><titles><title>10gram-scalesynthesisofachiraloxazolineiminopyridineligandanditsapplications</title><secondary-title>OrganicChemistryFrontiers</secondary-title></titles><periodical><full-title>OrganicChemistryFrontiers</full-title></periodical><pages>247-253</pages><volume>5</volume><number>2</number><section>247</section><dates><year>2018</year></dates><isbn>2052-4129</isbn><urls></urls><electronic-resource-num>10.1039/c7qo00816c</electronic-resource-num></record></Cite></EndNote>9，12,ADDINEN.CITEADDINEN.CITE.DATA13,14及一些已實現(xiàn)大規(guī)模應(yīng)用的人名反應(yīng)，通過教學(xué)化改進，設(shè)計了以廉價鈷金屬催化的區(qū)域及立體選擇性末端炔烴的反馬氏硅氫化合成烯基硅中間體、并基于該中間體實現(xiàn)多種應(yīng)用轉(zhuǎn)化的教學(xué)實驗。通過本次實驗在豐富學(xué)生有機硅化學(xué)知識的同時，向?qū)W生傳達有機合成中間體的重要概念，建立學(xué)生應(yīng)用中間體，選擇中間體、設(shè)計中間體的初步認識，體會良好有機合成中間體的適用性及其帶來的不竭的方法學(xué)研究動力。具有較明確的故事性、目的性、理論性。實驗由兩中心六模塊組成（圖3），為中間體的準備及衍生化應(yīng)用，覆蓋基本操作面廣，涉及無水無氧操作技術(shù)、光化學(xué)反應(yīng)等，同時貼近經(jīng)典反應(yīng)與科技前沿，模塊化的形式也便于高校依據(jù)自身課程設(shè)置及硬件條件改編選用為教學(xué)實驗。鼓勵學(xué)生進行分組衍生化實驗，本實驗設(shè)計為衍生化應(yīng)用提供了三個參考方案，同時允許學(xué)生自行查閱文獻進行衍生化應(yīng)用并通過展示的形式來提升學(xué)生團隊合作能力、總結(jié)能力、表達能力，改變了原先死板的“照方抓藥”，提升學(xué)生學(xué)習(xí)興趣。圖SEQ圖\*ARABIC圖SEQ圖\*ARABIC3:兩中心六模塊示意圖2實驗部分2.1實驗原理本實驗由兩中心（中間體的準備、中間體的衍生化應(yīng)用）六模塊組成。2.1.1中間體的準備催化劑準備ADDINEN.CITE<EndNote><Cite><Author>Chen</Author><Year>2018</Year><RecNum>18</RecNum><DisplayText><styleface="superscript">12</style></DisplayText><record><rec-number>18</rec-number><foreign-keys><keyapp="EN"db-id="tzzrza5fc2xpate0rd65rvvlszrtp2a5d5pe"timestamp="1586966074">18</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Chen,Jianhui</author><author>Xi,Tuo</author><author>Lu,Zhan</author></authors></contributors><titles><title>10gram-scalesynthesisofachiraloxazolineiminopyridineligandanditsapplications</title><secondary-title>OrganicChemistryFrontiers</secondary-title></titles><periodical><full-title>OrganicChemistryFrontiers</full-title></periodical><pages>247-253</pages><volume>5</volume><number>2</number><section>247</section><dates><year>2018</year></dates><isbn>2052-4129</isbn><urls></urls><electronic-resource-num>10.1039/c7qo00816c</electronic-resource-num></record></Cite></EndNote>12圖SEQ圖\*ARABIC圖SEQ圖\*ARABIC4：催化劑準備反應(yīng)式合成烯基硅中間體ADDINEN.CITEADDINEN.CITE.DATA13,14通過合成準備的催化劑，合成芳香、脂肪兩類烯基硅中間體。圖6：烯基硅中間體的合成反應(yīng)機理圖圖6：烯基硅中間體的合成反應(yīng)機理圖SEQ圖\*ARABIC5：烯基硅中間體的合成反應(yīng)2.1.2烯基硅中間體的衍生化應(yīng)用應(yīng)用路線一：探究性實驗以衍生化實驗的分組進行，鼓勵學(xué)生查閱文獻、實施實驗、展示成果。應(yīng)用路線二：Hiyama偶聯(lián)ADDINEN.CITE<EndNote><Cite><Author>Du</Author><Year>2017</Year><RecNum>1</RecNum><DisplayText><styleface="superscript">11,15</style></DisplayText><record><rec-number>1</rec-number><foreign-keys><keyapp="EN"db-id="tzzrza5fc2xpate0rd65rvvlszrtp2a5d5pe"timestamp="1586930297">1</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Du,Xiaoyong</author><author>Hou,Wenjun</author><author>Zhang,Yanlu</author><author>Huang,Zheng</author></authors></contributors><titles><title>Pincercobaltcomplex-catalyzedZ-selectivehydrosilylationofterminalalkynes</title><secondary-title>OrganicChemistryFrontiers</secondary-title></titles><periodical><full-title>OrganicChemistryFrontiers</full-title></periodical><pages>1517-1521</pages><volume>4</volume><number>8</number><section>1517</section><dates><year>2017</year></dates><isbn>2052-4129</isbn><urls></urls><electronic-resource-num>10.1039/c7qo00250e</electronic-resource-num></record></Cite><Cite><Author>Hatanaka</Author><Year>1988</Year><RecNum>19</RecNum><record><rec-number>19</rec-number><foreign-keys><keyapp="EN"db-id="tzzrza5fc2xpate0rd65rvvlszrtp2a5d5pe"timestamp="1587043645">19</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Hatanaka,Yasuo</author><author>Hiyama,Tamejiro</author></authors></contributors><titles><title>Cross-couplingoforganosilaneswithorganichalidesmediatedbyapalladiumcatalystandtris(diethylamino)sulfoniumdifluorotrimethylsilicate</title><secondary-title>TheJournalofOrganicChemistry</secondary-title></titles><periodical><full-title>TheJournalofOrganicChemistry</full-title></periodical><pages>918-920</pages><volume>53</volume><number>4</number><section>918</section><dates><year>1988</year></dates><isbn>0022-3263 1520-6904</isbn><urls></urls><electronic-resource-num>10.1021/jo00239a056</electronic-resource-num></record></Cite></EndNote>11,15以學(xué)生自行準備的脂肪族烯基硅與取代碘苯進行偶聯(lián)衍生化。此反應(yīng)有諸多優(yōu)點，包括高原子經(jīng)濟、對環(huán)境影響小、有機硅試劑容易儲存、易于操作、低毒性、反應(yīng)條件溫和、產(chǎn)率和選擇性高以及對其他官能團的耐受性較好等，Hiyama偶聯(lián)是對本類烯基硅化合物的巨大需求之一，也是諸多構(gòu)建烯基硅有機方法學(xué)的重要動力。圖圖7：Hiyama偶聯(lián)反應(yīng)圖8：圖8：Hiyama偶聯(lián)反應(yīng)機理應(yīng)用路線三：異構(gòu)化反應(yīng)ADDINEN.CITE<EndNote><Cite><Author>Fa?bender</Author><Year>2019</Year><RecNum>3</RecNum><DisplayText><styleface="superscript">9</style></DisplayText><record><rec-number>3</rec-number><foreign-keys><keyapp="EN"db-id="tzzrza5fc2xpate0rd65rvvlszrtp2a5d5pe"timestamp="1586930376">3</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Fa?bender,SvenjaI.</author><author>Molloy,JohnJ.</author><author>Mück‐Lichtenfeld,Christian</author><author>Gilmour,Ryan</author></authors></contributors><titles><title>GeometricE→ZIsomerisationofAlkenylSilanesbySelectiveEnergyTransferCatalysis:StereodivergentSynthesisofTriarylethylenesviaaFormalanti‐Metallometallation</title><secondary-title>AngewandteChemie</secondary-title></titles><periodical><full-title>AngewandteChemie</full-title></periodical><pages>18792-18799</pages><volume>131</volume><number>51</number><section>18792</section><dates><year>2019</year></dates><isbn>0044-8249 1521-3757</isbn><urls></urls><electronic-resource-num>10.1002/ange.201910169</electronic-resource-num></record></Cite></EndNote>9圖9：異構(gòu)化反應(yīng)以學(xué)生自行準備的芳香族烯基硅進行雙鍵光化學(xué)異構(gòu)化反應(yīng)。在設(shè)計合成化合物的過程中，對Z/E構(gòu)型的烯基硅開發(fā)出了諸多實現(xiàn)方法，以獲取不同種類的有機合成區(qū)塊。E圖9：異構(gòu)化反應(yīng)圖10：圖10：異構(gòu)化反應(yīng)機理應(yīng)用路線四：硅醇化反應(yīng)ADDINEN.CITE<EndNote><Cite><Author>Denmark</Author><Year>2006</Year><RecNum>2</RecNum><DisplayText><styleface="superscript">10</style></DisplayText><record><rec-number>2</rec-number><foreign-keys><keyapp="EN"db-id="tzzrza5fc2xpate0rd65rvvlszrtp2a5d5pe"timestamp="1586930361">2</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Denmark,S.E.</author><author>Neuville,L.</author><author>Christy,M.E.</author><author>Tymonko,S.A.</author></authors></contributors><auth-address>RogerAdamsLaboratory,DepartmentofChemistry,UniversityofIllinois,Urbana,Illinois61801,USA.denmark@</auth-address><titles><title>Aqualitativeexaminationoftheeffectsofsiliconsubstituentsontheefficiencyofcross-couplingreactions</title><secondary-title>JOrgChem</secondary-title></titles><periodical><full-title>JOrgChem</full-title></periodical><pages>8500-9</pages><volume>71</volume><number>22</number><edition>2006/10/27</edition><keywords><keyword>Alkenes/*chemistry</keyword><keyword>MolecularStructure</keyword><keyword>OrganosiliconCompounds/*chemicalsynthesis/*chemistry</keyword><keyword>Silanes/*chemistry</keyword></keywords><dates><year>2006</year><pub-dates><date>Oct27</date></pub-dates></dates><isbn>0022-3263(Print) 0022-3263(Linking)</isbn><accession-num>17064026</accession-num><urls><related-urls><url>/pubmed/17064026</url></related-urls></urls><electronic-resource-num>10.1021/jo061481t</electronic-resource-num></record></Cite></EndNote>10圖11：硅醇化反應(yīng)以學(xué)生自行準備的脂肪族烯基硅進行氧化硅醇化。硅醇可以用作激活羰基化合物的有機催化劑、碳氫鍵活化的導(dǎo)向基、或在藥物開發(fā)上扮演一個可能的活性結(jié)構(gòu)。硅醇的合成手段也發(fā)展了很多方法，而本次我們將利用常見已圖11：硅醇化反應(yīng)2.2主要試劑或材料9,9-二甲基-4,5-雙二苯基膦氧雜蒽；無水溴化鈷；醋酸鈀；1,4-雙（二苯膦）丁烷；二苯甲酮；1-己炔；苯乙炔；叔丁醇鈉；4-碘三氟甲苯；四丁基氟化銨；碳酸氫鉀；過氧化氫（30%）；環(huán)己烷；甲醇；乙醚；甲苯；四氫呋喃；石油醚；乙酸乙酯；氯化鈉；硫酸鎂；氮氣（瓶）。2.3主要儀器和表征方法Schlenk反應(yīng)瓶；單口、雙口圓底燒瓶；量筒；（微量）注射器；大試管；遮光布；聚四氟乙烯軟管；球形冷凝管；分液漏斗；恒壓分液漏斗；油浴鍋；水浴鍋；硅膠色譜柱；布氏漏斗；砂芯漏斗；吸濾瓶；磁力攪拌儀；電子天平；365nm紫外燈；循環(huán)水真空泵；減壓油泵；減壓旋蒸儀；電吹風(fēng)；烘槍；烘箱；400M液體核磁共振儀。2.4實驗步驟/方法（有機化合物分析結(jié)果見文末支撐材料）2.4.1中間體的準備催化劑準備氮氣氛圍下，往100mL干燥的Schlenk反應(yīng)瓶中依次加入Xantphos(1.7359g,3mmol),THF(30mL)和無水CoBr2(0.5950g,2.72mmol)，室溫下攪拌3小時。反應(yīng)完成后反應(yīng)管中加入15mL乙醚，過濾，真空干燥得到綠色固體。合成烯基硅中間體將25mLSchlenk反應(yīng)管從烘箱中取出，安裝后抽排氣三次（有條件可以使用烘槍或吹風(fēng)機加熱抽氣），打開氮氣球開關(guān)，將CoBr2?Xantphos（0.005mmol,0.0041g,1mol%）加入到25mL干燥的Schlenk反應(yīng)瓶中，置換氣一次。然后按順序用微量注射器加入二苯基硅烷（0.5mmol，93μL），置換氣一次；加入叔丁醇鈉（0.075mmol,0.0072g,15mol%），置換氣一次。最后慢慢地用微量注射器逐滴滴加炔烴（1.0mmol,己炔與苯乙炔均為55μL）。注意所有反應(yīng)物不要黏在瓶壁，且過快地滴加炔烴會導(dǎo)致區(qū)域選擇性和產(chǎn)率下降。室溫下無溶劑攪拌10min，加入15mL石油醚和5mL乙酸乙酯淬滅反應(yīng)，硅膠過濾，用30mL石油醚洗滌，合并。濾液經(jīng)旋蒸除去溶液并抽干，加入10μLTMSPh作為內(nèi)標(biāo)，經(jīng)核磁氫譜確定反應(yīng)產(chǎn)率以及選擇性。粗產(chǎn)物以石油醚為洗脫劑，經(jīng)柱層析分離，核磁共振氫譜確定分離產(chǎn)物。2.4.2烯基硅中間體的衍生化應(yīng)用（選做模塊）由于衍生化應(yīng)用所需的操作較多，因而在默認全選的情況下，建議以三人為小組的形式進行，小組應(yīng)該在授課前完成。應(yīng)用路線一：探究性實驗以三人小組的單位查詢不同于提供方案的烯基硅衍生化應(yīng)用途徑，報教師進行探究。完成探究后，可通過課程論文，課堂展示的形式對學(xué)生的探究成果進行考察，并納入平時分統(tǒng)計。下文提供了三種參考方案，也可以直接選取方案編寫為非探究性實驗進行教學(xué)。應(yīng)用路線二：Hiyama偶聯(lián)氮氣條件下，在25mLSchlenk反應(yīng)管依次加入磁子和二苯基-((E)-2-己烯基)硅烷(分子量是266.458，0.0667g,0.25mmol)，0.5mlTBAF(0.5mmol,THF1.0M)，攪拌5min，依次加入三氟甲基碘苯(0.0408g,0.2mmol)，Pd(OAc)2(5.8mg,0.025mmol)，dppb(10.6mg,0.025mol)。反應(yīng)混合物在30℃下攪拌6h，有機溶劑稀釋，然后將溶液暴露于空氣中進行猝滅，過濾旋干，加入10μLTMSPh作為內(nèi)標(biāo)，經(jīng)核磁氫譜確定反應(yīng)產(chǎn)率以及選擇性。粗產(chǎn)物經(jīng)柱層析（石油醚為洗脫劑），核磁共振氫譜確定分離產(chǎn)物。應(yīng)用路線三：異構(gòu)化反應(yīng)使用1mm內(nèi)徑，2mm外徑，全長五米的聚四氟乙烯軟管作為反應(yīng)管纏繞在大試管上，50mL圓底燒瓶作為接收瓶，配合燒杯、注射器等儀器依照下圖進行組裝，抽排氣三次。取苯基烯基硅（0.25mmol,0.0716g），二苯酮（0.0125mmol，0.0023g）溶解于于3mL環(huán)己烷中，使用注射器加入反應(yīng)管中，利用24W，365nm紫外燈帶進行照射反應(yīng)兩小時。反應(yīng)結(jié)束，注入7ml無水乙醇，以鼓氣泵吹入接收瓶中，重復(fù)三次。接收瓶中產(chǎn)物液體經(jīng)旋蒸除去溶液并抽干。加入10μLTMSPh作為內(nèi)標(biāo)，進行氫譜分析。轉(zhuǎn)化率約為30%。圖圖12：異構(gòu)化反應(yīng)裝置（左為置換氣裝置，右為反應(yīng)階段裝置，主要儀器分別為：1、大試管支撐的聚四氟乙烯反應(yīng)管2、接收瓶3、燈帶4、連接三通的氮氣球及抽氣泵5、加料注射器）應(yīng)用路線四：硅醇化反應(yīng)在50mL圓底燒瓶中依次加入苯基烯基硅（0.25mmol,0.0716g），3mLTHF，3mL甲醇，碳酸氫鉀（0.25mmol,0.0250g），逐滴滴加0.6mL30%過氧化氫，在室溫條件下攪拌3小時。加入5mL水淬滅，乙酸乙酯（15mL×3）萃取，無水硫酸鈉干燥后過濾旋干，固體上樣，粗產(chǎn)物以乙酸乙酯：石油醚=1：10為洗脫劑，經(jīng)柱層析分離，NMR確定分離產(chǎn)物。3參考思考題為便于讀者老師參考使用我們的實驗，此處我們設(shè)計思考題若干，供讀者參考：（1）為什么在鈷催化劑的合成中需要無水無氧操作？（2）無水無氧操作玻璃儀器、油泵使用時有什么注意事項？（3）紫外光反應(yīng)中，為保證實驗安全有哪些所需要注意的事項？（4）通過未純化的反應(yīng)粗產(chǎn)物確定轉(zhuǎn)化率的方法有哪些？4參考搭配針對我們所設(shè)計的模塊化實驗之特點與高校常開設(shè)的基礎(chǔ)類、中級有機化學(xué)實驗、有機合成（綜合化學(xué)）實驗，提出一些搭配方案供參考：基礎(chǔ)有機實驗方案1：催化劑合成+中間體合成 （5課時）基礎(chǔ)有機實驗方案2：中間體合成+硅醇化反應(yīng) （5課時）中級有機實驗方案1：催化劑合成+中間體合成+探究性實驗（8課時）中級有機實驗方案2：催化劑合成+中間體合成+應(yīng)用試驗一項（8課時）中級有機實驗方案3：中間體合成+應(yīng)用試驗兩項（8課時）有機合成實驗方案1：催化劑合成+中間體合成+探究性實驗（12課時）有機合成實驗方案2：催化劑合成+中間體合成+應(yīng)用試驗三項（12課時）5實驗創(chuàng)新點與優(yōu)勢（1）教學(xué)實驗與科學(xué)前沿、經(jīng)典反應(yīng)、逆合成理論相結(jié)合，提高學(xué)生學(xué)習(xí)興趣。（2）用量微小，成本較低，反應(yīng)時間短，適合學(xué)習(xí)微量反應(yīng)為代表的方法學(xué)實驗。（3）實驗原料易得，涉及多種有機結(jié)構(gòu)，產(chǎn)率好，幫助學(xué)生認識官能團容忍性概念。（4）涉及多種合成及分析操作，最大程度鍛煉學(xué)生化學(xué)綜合能力，助力研究生階段學(xué)習(xí)。6教學(xué)建議（1）化學(xué)試劑防護、氣體、光源的使