有机合成中间体概念综合教学实验

有机合成中间体概念综合教学实验——以烯基硅的高效合成与衍生化应用为例摘要：有机合成中间体是一个历史悠久，应用广泛的概念，在有机合成大师、诺贝尔奖获得者EliasJamesCorey提出了逆合成分析概念后，与合成子概念息息相关的有机合成中间体进一步发挥着中流砥柱的作用。烯基硅化合物由于其多功能反应性、低毒、稳定等特点在近年来备受瞩目，合成与应用方法层出不穷，成为了一个新兴的有机合成中间体。本实验项目将基于烯基硅中间体，把有机合成中间体概念引入到有机化学实验教学中。以制备与应用两个模块化实验内容为主体，改变了原先教学实验较为单一且缺乏故事性、目的性、理论性的特点，同时涉及经典人名反应Hiyama偶联及最新科研成果，覆盖了大量有机合成方法学研究和实验的基本操作、并通过探究性实验激发学生学习兴趣。本实验由模块化实验组成，允许高校较为容易地依照自身条件改编选用入课程教学中。关键词：有机合成中间体；逆合成分析；合成子；烯基硅化合物；Hiyama偶联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引言有机化学自1828年德国化学家魏勒（E.Wohler）借助无机化合物制备尿素发轫以来，已经与人类的生活息息相关，密不可分。在有机化学的产学研过程中，为获取所需要的有机化合物，人们常常要通过商业购买，或经由商业可得的原料自行合成。基于这样的需求，越来越多的化合物经由人们的研究和生产，成为了商业可得的有机合成原料，即有机合成中间体。图SEQ图\*ARABIC1：逆合成分析法在过去的几十年中，针对有机合成中间体的研究不断进行，远远超过了1951年数千的可得数量。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（图1）大大促进有机合成进步的同时，也加速了有机合成中间体的选择与开发——通过逆合成手段，我们通过不同切断逻辑获取合成子，并提供有机合成中间体来担当合成子等价试剂来实现逆合成分析与有机合成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%">有机合成：切断法（原书第</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%">科学出版社</style></publisher><isbn>9787030276704</isbn><urls></urls></record></Cite></EndNote>2。有机合成与有机合成中间体两个概念已然密不可分（图2）。通过教学实验掌握中间体构建、应用的知识点，将有利于化学、药学等专业专业素质的培养。图SEQ图\*ARABIC1：逆合成分析法图SEQ图\*ARABIC2:有机合成与有机合成中间体：a)格氏试剂的亲核反应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,Pål</author><author>Rømming,Christian</author><author>Rise,Frode</author><author>Hartshorn,MichaelP.</author><author>Merchán,Manuela</author><author>Robinson,WardT.</author><author>Roos,BjörnO.</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)镁卤交换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)环氧开环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)制备酚醛树脂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)制备苦味酸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)制备三溴苯酚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)双键异构化ADDINEN.CITE<EndNote><Cite><Author>Faßbender</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>Faßbender,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)硅醇转换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偶联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年诺贝尔化学奖授予Heck,Negishi和Suzuki，表彰他们在交叉偶联反应方面做出的杰出贡献。偶联反应对于现代合成化学、医药领域和活性生物分子的合成至关重要，人们利用偶联反应高效地合成了各种复杂的分子，而偶联反应离不开三种元素——硼、硅和锡。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，有机硅材料在生产生活中应用广泛，例如线性聚硅氧烷产品——硅油是常见的润滑剂、添加剂和油浴的热载体。有机硅中间体同样也是有机合成的重要合成砌块，正是由于其较好的稳定性和多种的转化途径，它可以为之后进行精准构筑碳碳键或碳氧键以及修饰硅原子上的基团提供便利。但是在本科理论教学和实验教学中缺少对有机硅化学的讲解，存在一定空白与填补空间。基于以上教学目标，我们所设计的教学实验，将围绕逆合成分析法所紧密结合的有机合成中间体概念进行。以新兴有机硅中间体——烯基硅中间体的高效合成与衍生化应用为例，选择了合成方法学领域发表的较新科研成果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及一些已实现大规模应用的人名反应，通过教学化改进，设计了以廉价钴金属催化的区域及立体选择性末端炔烃的反马氏硅氢化合成烯基硅中间体、并基于该中间体实现多种应用转化的教学实验。通过本次实验在丰富学生有机硅化学知识的同时，向学生传达有机合成中间体的重要概念，建立学生应用中间体，选择中间体、设计中间体的初步认识，体会良好有机合成中间体的适用性及其带来的不竭的方法学研究动力。具有较明确的故事性、目的性、理论性。实验由两中心六模块组成（图3），为中间体的准备及衍生化应用，覆盖基本操作面广，涉及无水无氧操作技术、光化学反应等，同时贴近经典反应与科技前沿，模块化的形式也便于高校依据自身课程设置及硬件条件改编选用为教学实验。鼓励学生进行分组衍生化实验，本实验设计为衍生化应用提供了三个参考方案，同时允许学生自行查阅文献进行衍生化应用并通过展示的形式来提升学生团队合作能力、总结能力、表达能力，改变了原先死板的“照方抓药”，提升学生学习兴趣。图SEQ图\*ARABIC图SEQ图\*ARABIC3:两中心六模块示意图2实验部分2.1实验原理本实验由两中心（中间体的准备、中间体的衍生化应用）六模块组成。2.1.1中间体的准备催化剂准备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图SEQ图\*ARABIC图SEQ图\*ARABIC4：催化剂准备反应式合成烯基硅中间体ADDINEN.CITEADDINEN.CITE.DATA13,14通过合成准备的催化剂，合成芳香、脂肪两类烯基硅中间体。图6：烯基硅中间体的合成反应机理图图6：烯基硅中间体的合成反应机理图SEQ图\*ARABIC5：烯基硅中间体的合成反应2.1.2烯基硅中间体的衍生化应用应用路线一：探究性实验以衍生化实验的分组进行，鼓励学生查阅文献、实施实验、展示成果。应用路线二：Hiyama偶联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以学生自行准备的脂肪族烯基硅与取代碘苯进行偶联衍生化。此反应有诸多优点，包括高原子经济、对环境影响小、有机硅试剂容易储存、易于操作、低毒性、反应条件温和、产率和选择性高以及对其他官能团的耐受性较好等，Hiyama偶联是对本类烯基硅化合物的巨大需求之一，也是诸多构建烯基硅有机方法学的重要动力。图图7：Hiyama偶联反应图8：图8：Hiyama偶联反应机理应用路线三：异构化反应ADDINEN.CITE<EndNote><Cite><Author>Faßbender</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>Faßbender,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图9：异构化反应以学生自行准备的芳香族烯基硅进行双键光化学异构化反应。在设计合成化合物的过程中，对Z/E构型的烯基硅开发出了诸多实现方法，以获取不同种类的有机合成区块。E图9：异构化反应图10：图10：异构化反应机理应用路线四：硅醇化反应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图11：硅醇化反应以学生自行准备的脂肪族烯基硅进行氧化硅醇化。硅醇可以用作激活羰基化合物的有机催化剂、碳氢键活化的导向基、或在药物开发上扮演一个可能的活性结构。硅醇的合成手段也发展了很多方法，而本次我们将利用常见已图11：硅醇化反应2.2主要试剂或材料9,9-二甲基-4,5-双二苯基膦氧杂蒽；无水溴化钴；醋酸钯；1,4-双（二苯膦）丁烷；二苯甲酮；1-己炔；苯乙炔；叔丁醇钠；4-碘三氟甲苯；四丁基氟化铵；碳酸氢钾；过氧化氢（30%）；环己烷；甲醇；乙醚；甲苯；四氢呋喃；石油醚；乙酸乙酯；氯化钠；硫酸镁；氮气（瓶）。2.3主要仪器和表征方法Schlenk反应瓶；单口、双口圆底烧瓶；量筒；（微量）注射器；大试管；遮光布；聚四氟乙烯软管；球形冷凝管；分液漏斗；恒压分液漏斗；油浴锅；水浴锅；硅胶色谱柱；布氏漏斗；砂芯漏斗；吸滤瓶；磁力搅拌仪；电子天平；365nm紫外灯；循环水真空泵；减压油泵；减压旋蒸仪；电吹风；烘枪；烘箱；400M液体核磁共振仪。2.4实验步骤/方法（有机化合物分析结果见文末支撑材料）2.4.1中间体的准备催化剂准备氮气氛围下，往100mL干燥的Schlenk反应瓶中依次加入Xantphos(1.7359g,3mmol),THF(30mL)和无水CoBr2(0.5950g,2.72mmol)，室温下搅拌3小时。反应完成后反应管中加入15mL乙醚，过滤，真空干燥得到绿色固体。合成烯基硅中间体将25mLSchlenk反应管从烘箱中取出，安装后抽排气三次（有条件可以使用烘枪或吹风机加热抽气），打开氮气球开关，将CoBr2•Xantphos（0.005mmol,0.0041g,1mol%）加入到25mL干燥的Schlenk反应瓶中，置换气一次。然后按顺序用微量注射器加入二苯基硅烷（0.5mmol，93μL），置换气一次；加入叔丁醇钠（0.075mmol,0.0072g,15mol%），置换气一次。最后慢慢地用微量注射器逐滴滴加炔烃（1.0mmol,己炔与苯乙炔均为55μL）。注意所有反应物不要黏在瓶壁，且过快地滴加炔烃会导致区域选择性和产率下降。室温下无溶剂搅拌10min，加入15mL石油醚和5mL乙酸乙酯淬灭反应，硅胶过滤，用30mL石油醚洗涤，合并。滤液经旋蒸除去溶液并抽干，加入10μLTMSPh作为内标，经核磁氢谱确定反应产率以及选择性。粗产物以石油醚为洗脱剂，经柱层析分离，核磁共振氢谱确定分离产物。2.4.2烯基硅中间体的衍生化应用（选做模块）由于衍生化应用所需的操作较多，因而在默认全选的情况下，建议以三人为小组的形式进行，小组应该在授课前完成。应用路线一：探究性实验以三人小组的单位查询不同于提供方案的烯基硅衍生化应用途径，报教师进行探究。完成探究后，可通过课程论文，课堂展示的形式对学生的探究成果进行考察，并纳入平时分统计。下文提供了三种参考方案，也可以直接选取方案编写为非探究性实验进行教学。应用路线二：Hiyama偶联氮气条件下，在25mLSchlenk反应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)，搅拌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)。反应混合物在30℃下搅拌6h，有机溶剂稀释，然后将溶液暴露于空气中进行猝灭，过滤旋干，加入10μLTMSPh作为内标，经核磁氢谱确定反应产率以及选择性。粗产物经柱层析（石油醚为洗脱剂），核磁共振氢谱确定分离产物。应用路线三：异构化反应使用1mm内径，2mm外径，全长五米的聚四氟乙烯软管作为反应管缠绕在大试管上，50mL圆底烧瓶作为接收瓶，配合烧杯、注射器等仪器依照下图进行组装，抽排气三次。取苯基烯基硅（0.25mmol,0.0716g），二苯酮（0.0125mmol，0.0023g）溶解于于3mL环己烷中，使用注射器加入反应管中，利用24W，365nm紫外灯带进行照射反应两小时。反应结束，注入7ml无水乙醇，以鼓气泵吹入接收瓶中，重复三次。接收瓶中产物液体经旋蒸除去溶液并抽干。加入10μLTMSPh作为内标，进行氢谱分析。转化率约为30%。图图12：异构化反应装置（左为置换气装置，右为反应阶段装置，主要仪器分别为：1、大试管支撑的聚四氟乙烯反应管2、接收瓶3、灯带4、连接三通的氮气球及抽气泵5、加料注射器）应用路线四：硅醇化反应在50mL圆底烧瓶中依次加入苯基烯基硅（0.25mmol,0.0716g），3mLTHF，3mL甲醇，碳酸氢钾（0.25mmol,0.0250g），逐滴滴加0.6mL30%过氧化氢，在室温条件下搅拌3小时。加入5mL水淬灭，乙酸乙酯（15mL×3）萃取，无水硫酸钠干燥后过滤旋干，固体上样，粗产物以乙酸乙酯：石油醚=1：10为洗脱剂，经柱层析分离，NMR确定分离产物。3参考思考题为便于读者老师参考使用我们的实验，此处我们设计思考题若干，供读者参考：（1）为什么在钴催化剂的合成中需要无水无氧操作？（2）无水无氧操作玻璃仪器、油泵使用时有什么注意事项？（3）紫外光反应中，为保证实验安全有哪些所需要注意的事项？（4）通过未纯化的反应粗产物确定转化率的方法有哪些？4参考搭配针对我们所设计的模块化实验之特点与高校常开设的基础类、中级有机化学实验、有机合成（综合化学）实验，提出一些搭配方案供参考：基础有机实验方案1：催化剂合成+中间体合成 （5课时）基础有机实验方案2：中间体合成+硅醇化反应 （5课时）中级有机实验方案1：催化剂合成+中间体合成+探究性实验（8课时）中级有机实验方案2：催化剂合成+中间体合成+应用试验一项（8课时）中级有机实验方案3：中间体合成+应用试验两项（8课时）有机合成实验方案1：催化剂合成+中间体合成+探究性实验（12课时）有机合成实验方案2：催化剂合成+中间体合成+应用试验三项（12课时）5实验创新点与优势（1）教学实验与科学前沿、经典反应、逆合成理论相结合，提高学生学习兴趣。（2）用量微小，成本较低，反应时间短，适合学习微量反应为代表的方法学实验。（3）实验原料易得，涉及多种有机结构，产率好，帮助学生认识官能团容忍性概念。（4）涉及多种合成及分析操作，最大程度锻炼学生化学综合能力，助力研究生阶段学习。6教学建议（1）化学试剂防护、气体、光源的使