第一讲 绪论ppt课件

.,精细有机合成设计及应用DesigningOrganicSynthesis,化学化工学院,主讲高远浩,.,绪论,一、旧有机合成反应的类型二、有机合成的任务三、有机合成的历史回顾四、精细有机合成发展趋势和重点五、学习内容和方法六、重要参考书及期刊七、课程安排八、合成基础能力测试,.,一、旧有机合成反应的类型,旧有机合成反应的类型：,.,二、有机合成的任务,.,1.基本有机合成工业,二、有机合成的任务,2.精细有机合成工业,以乙醇、乙酸、丙酮、甲烷、乙炔、苯、萘等为原料，合成一些结构比较复杂，质量要求很高的农药、燃料、颜料、高纯试剂、食品添加剂、日用化学品、信息用化学品、功能高分子材料等等。,.,.,总收率只有,0.79%,.,.,对有机合成者的要求：,1.应熟练掌握单元合成反应,.,2.把握好合成战略,.,三、有机合成的历史回顾,1.尿素的合成（1828年，德国化学家Wohler）,有机化学的开始,.,.,2.颠茄酮的合成,1)1902年，德国化学家Willstatter(1915年获Noble化学奖）,21steps,overallyield0.7%,.,2）1917年，英国化学家Robinson(1947年获Noble化学奖）,3steps,overallyield90%,Robinson为什么能是发现这条合成路线？,MannichReaction(曼尼希反应1912),.,3.维生素B12的合成（Woodward,1977年）,在Woodward领导下,经过两个实验室，100多位科学家的共同努力，于1977年完成了维生素B12的全合成工作。将有机合成作为一种艺术展现在世人面前。,Woodward（伍德沃德）因在1945-1954年人工合成了奎宁、类固醇、马钱子碱、羊毛甾醇、麦角碱等近20种复杂天然产物而1965年获Noble化学奖,.,.,.,E.J.Corey,(1990年获Noble化学奖),如果说Woodward一生奋斗的成就是将有机合成作为一种艺术展现在世人面前，那么Corey(科里）则是将有机合成从艺术转变成为科学的一个关键人物。他的逆合成分析是现代有机合成化学的重要基石，推动了20世纪70年代以来整个有机合成领域的蓬勃发展。,科里的逆合成分析(Retrosyntheticanalysis),.,Woodward(1981)红霉素的全合成,Y.Kishi(1987)海葵毒素的全合成,S.L.Schreiberetal(1993)FK-1012的全合成,K.C.Nicolaou动力学控制条件下主要生成取代基较少的烯醇;,Example1,.,Example2,.,3.立体选择性（Steroselectivity),烯醇化合物的立体选择性形成,将为不对称合成提供平台.,.,Example1,.,Example2,.,Example3,.,Example4,.,4.二羰基化合物的-烷基化反应(-Alkylationof1,3-dicarbonylcompounds),J.Am.Chem.Soc.,1974,90,1082;1963,85,3237;1965,87,82.,Example1,.,Example2,.,Example3,继承与发展,.,5.芳基卤化物与烯醇盐的反应(Reactionsofaromatichalidewithenolates),Example,Mechanism,.,关键是要有形成苯炔的条件。,.,6.酮和酯的烷基化反应(Alkylationsofketonesandesters),避免Aldol缩合反应发生的方法：烷化剂要待酮完全转化为烯醇式后再加入。,常用的碱：NaNH2,KNH2,NaH,Ph3CNa等；有副产物。LDA,LTMP,LHMDS等效果很好。,.,Example1,Example2,.,不对称酮的选择性烷基化反应(Selectivealkylationofasymmetricketones),在一个-位引入一个活化基(略）如：DieckmannReaction;Claisencondensation,制成结构专属性的烯醇负离子,.,在取代基较多的-位烷基化(烯醇硅醚法),碱性条件,.,酸性条件,.,在取代基较少的-位烷基化(烯胺法,StorkEnamineSynthesis),通常，用活泼的卤代烷，可以高产率生成C-烷基化产物；但对于一般的卤代烃，C-烷基化产物收率较底。若用LDA在低温下反应，则对各种卤代烃均可得到高收率的C-烷基化产物。对于不对称酮，主要在取代基较少的-位发生烷基化。,.,Example1,Example2,.,7.对映选择性烷基化反应（Enantioselectivealkylations),利用手性胺,.,利用二甲基肼,.,扩展：二甲基腙锂化合物的另一应用,二甲基腙锂化合物容易转化成有机铜化合物，而有机铜化合物在C-C键的形成中很有用。,.,利用SAMP和RAMP,若用RAMP，则得到另一种对映异构体。,.,羧酸的-不对称烷基化,.,Example,.,8.极性翻转（Umpolung),俞凌翀，刘志昌，极性转换及其在有机合成中的应用，科学出版社，1991,Example1安息香缩合,.,Example2醛氰醇法,.,Example31,3二噻烷法,不易发生Michael加成反应。,.,Example4乙基乙硫甲基亚砜法,1,4二酮,.,四、缩合反应(Condensation),AldolReactionMichaelAdditionMannichReactionClaisenCondensationDieckmannCondrnsationDarzensReactionReformatslyreaction,.,AldolReaction(condensation),1)经典Aldol反应的两大缺点,不同醛、酮之间的反应常得到混合产物；立体选择性差,.,2)定向醇醛缩合反应（DirectedAldolcondensation),Metood1PreformedLithiumEnolates,Z-enolatesgivepredominantlysyn(orthreo)aldolproducts(thermodynamicenolates).E-enolatesgivepredominantlyanti(orerythro)aldolproducts(kineticenolates).,.,Example1,-StericsizeofR1affectsdiastereoselectivity,.,.,OriginofDiastereoselectivity,a.Z-enolates,DiastereoselectivityforZ-enolate(givingsynaldolproduct)ismaximizedwhenR1andR3arestericallydemanding(R1/R3interactionismaximized).Diastereoselectivityalsoincreasesasmetalischangedtoboron.ThisisattritubtedtoatighterT.S.(BObondshorter,soR1/R3stericinteractionsaremagnifiedinT.S.forantiproduct).WhenR2isverylargetheR3/R2gaucheinteractionR1/R31,3-diaxialinteraction(Why?).,.,b.E-enolates,DiastereoselectivityincreasesasR1andR3becomestericallylarge,andaswitchtotheboronenolatewillincreaseselectivity.DiastereoselectivitymayswitchwhenR2isverylarge(Why?).,.,EffectofR1,.,EffectofR3,.,EffectofR2,.,Metood2PreformedBoronEnolates,.,.,a.Z-enolatePreparationandReactions,.,b.E-enolatePreparationandReactions,.,-Originallydifficulttocontrolbut:,.,c.Examplesofmorerecentmethodstocontrolboronenolategeometry,.,.,AldolCondensationwithChiralEnolates,.,.,TienolatepromotedEvansaldol(non-Evanssynaldol),.,Chelatedandnon-chelatedTienolates,.,Metood3Acid-CatalysedDirectedAldolReactions,该方法是在酸性条件下反应；但立体选择性较差。,.,3)有机小分子催化醇醛缩合反应,（SmallOrganicMoleculesCatalystedAldolReactions),.,.,.,.,.,.,NovelSmallOrganicMoleculesforaHighlyEnantioselectiveDirectAldolReaction,J.AM.CHEM.SOC.2003,125,5262-5263,ZhuoTang,FanJiang,Luo-TingYu,XinCui,Liu-ZhuGong,*,Ai-QiaoMi,Yao-ZhongJiang,andYun-DongWu*,KeyLaboratoryforAsymmetricSynthesisandChirotechnologyofSichuanProvince,ChengduInstituteofOrganicChemistry,ChineseAcademyofSciences,Chengdu,610041,China,CollegeofChemicalEngineering,SichuanUniVersity,Chengdu,610065,China,andStateKeyLaboratoryofMolecularDynamicsandStableStructures,CollegeofChemistryandMolecularEngineering,PekingUniVersity,Beijing,100871,China,.,.,.,.,2.MichaelAdditionReaction,Applications:Synthesisof1,5-dicarbonylcompounds,GeneralScheme,.,Development:AsymmetryMichaelAdditionReaction,手性金属配位化合物催化,.,MacmillanGroupsWork,SmallOrganicMoleculecatalyzedasymmetricMichaelreactions,.,.,.,TheFirstEnantioselectiveOrganocatalyticMukaiyama-MichaelReaction:,.,S.P.Brown,N.C.Goodwin,andD.W.C.MacMillan*,J.Am.Chem.Soc.2003,125(5),1192-1194,.,3.MannichReaction,GeneralScheme,胺组份氨、伯胺、仲胺,醛组份HCHO,PhCHO,RCHO,可分别发生三、双、单Mannich反应,活泼H组份,醛、酮、活泼亚甲基化合物、酚类化合物、杂环、炔等。,.,Example2,Example1,.,Development:AsymmetryMannichReaction,Lewisacid-catalyzedasymmetricMannichreactions,(a)Fujii,A.;Hagiwara,E.;Sodeoka,M.J.Am.Chem.Soc.1999,121,5450;(b)Ishitani,H.;Ueno,M.;Kobayashi,S.J.Am.Chem.Soc.2000,122,8180;(c)Ishihara,K.;Miyata,M.;Hattori,K.;Yamamoto,H.J.Am.Chem.Soc.1994,116,10520;(d)Ishitani,H.;Ueno,M.;Kobayashi,S.J.Am.Chem.Soc.1997,119,2060;(e)Ferraris,D.;Yong,B.;Dudding,T.;Leckta,T.J.Am.Chem.Soc.1998,120,4548;(f)Ferraris,D.;Young,B.;Cox,C.;Dudding,T.;Drury,W.J.,III;Ryzhkov,L.;Taggi,A.E.;Lectka,T.J.Am.Chem.Soc.2002,124,67.(g)Kobayashi,S.;Hamada,T.;Manabe,K.J.Am.Chem.Soc.2002,124,5640.,.,(a)Notz,W.;Sakthivel,K.;Bui,T.;Zhong,G.;Barbas,C.F.,IIITetrahedronLett.2001,42,199;(b)Juhl,K.;Gathergood,N.;Jorgensen,K.A.Angew.Chem.,Int.Ed.2001,40,2995;(c)Yamasaki,S.;Iida,T.;Shibasaki,M.Tetrahedron1999,55,8857;(d)List,B.J.Am.Chem.Soc.2000,122,9336;(e)Cordova,A.;Notz,W.;Zhong,G.;Betancort,J.M.;Barbas,C.F.,IIIJ.Am.Chem.Soc.2002,124,1842;(f)Cordova,A.;Watanabe,S.-i.;Tanaka,F.;Notz,W.;Barbas,C.F.,IIIJ.Am.Chem.Soc.2002,124,1866.,SmallOrganicMoleculecatalyzedasymmetricMannichreactions,.,.,.,TheDirectandEnantioselective,One-Pot,Three-Component,Cross-MannichReactionofAldehydes,Angew.Chem.Int.Ed.2003,42,36773680,Y.Hayashi,W.Tsuboi,I.Ashimine,T.Urushima,Dr.M.ShojiDepartmentofIndustrialChemistry,FacultyofEngineeringTokyoUniversityofScience,Kagurazaka,.,Three-componentMannichreactionwithvariousacceptoraldehydes,N-methyl-2-pyrrolidinone(NMP),.,Three-componentMannichreactionwithvariousdonoraldehydes.,.,4.ClaisenCondensation,GeneralScheme,Mechanism,.,一种酯的自身缩合,Scopeofapplication,一种含-H的酯与一种不含-H的酯之间的缩合,Examples,.,DirectedClaisencondensation,.,5.DickmannCondensation,.,.,.,Chapter3FormationofCarbon-CarbonDouleBonds,.,1.-Eleminationreactions（-消去反应）,I.TheSyntheticMethodsofAlklenes,.,2.Pyrolyticsyneliminations（顺式热消去反应）,Applications:Synthesisofterminalalkenesfromprimaryacetates,Disadvantages:Highreactiontemperature,.,Copereaction,Chugavereaction,反应条件比对应的酯热消去温和。,.,3.Wittigandrelatedreactions（Wittig及有关反应）,WittigReaction,G.Wittigreceivedthe1979NobelPrizeinChemistryformanysignificantcontributionstoOrganicChemistrywhichincludednotonlytheWittigreaction,butalsoPhLipreparedbymetal-halogenexchange,benzyne,andtheWittigrearrangement.,.,GeneralScheme,Mildreactionconditions;Thepositionofthedoublebondisunambiguous.,Features,.,RepresentativeExamples,Example1,Example2,.,Example3,Example4,.,Mechanism,2+2cycloaddition.,.,Influenceofsolventontheselectivity,ActivityandstereoselectivityofYild,.,Schlssermodification:allowsthepreparationoftransvs.cisolefins.,SchlsserAngew.Chem.,Int.Ed.Eng.1966,5,126.,.,StabilizedYlides,-Stabilizedylidesaresolid;stabletostorage,notparticularlysensitivetomoisture,andcanevenbepurifiedbychromatography.,-Becausetheyarestabilized,theyaremuchlessreactivethanalkylylides.Theyreactwellwithaldehydes,butonlyslowlywithketones.,-Thefirststep,involvingtheadditiontothealdehyde,isslowandreversiblewithstabilizedylides.,.,.,Influenceofsolventontheselectivity,.,WadsworthHornerEmmonsReaction,HornerChem.Ber.1958,91,61;1959,92,2499.Wadsworth,EmmonsJ.Am.Chem.Soc.1961,83,1733.,Reviews:Org.React.1977,25,73253.ComprehensiveOrg.Syn.,Vol.1,761.,.,PreparationofPhosphonateEsters,ArbuzovJ.Russ.Phys.Chem.Soc.1906,38,687.,-ArbuzovRearragement,-Thesameapproachtothepreparationof-ketophosphonatesisnotsuccessful:,.,-ButcanusevariationonClaisenconditions:,.,ModificationsandScope,-LiCl/tertiaryamines(DBU,iPr2NEt,Et3N),Masamune,RoushTetrahedronLett.1984,25,2183.,Cansubstituteforconventionalconditionsandisespeciallygoodforbasesensitivesubstrates.,.,-HinderedphosphonatesandhinderedaldehydesincreaseE-selectivity(trans).,-StillGennarimodificationselectiveforZ-alkenes(cis):,.,-AdditionalZ-selectivestabilizedphosphonates.,SelecteddiarylphosphonatesprovideHighZ-selectivityaswell.,.,PetersonReaction,Reviews:Org.React.1990,38,1.,PetersonreactionoffersanalternativetoWittigprocedure.TheyaremorereactiveandstericallylessdemandingthanaWittigreagentandthevolatilebyproduct(Me3SiOH/Me3SiOSiMe3)issimplertoremovethanPh3PO.Itdoes,however,requireasecondsteptopromoteeliminationofthe-hydroxysilane.,.,-Theeliminationisstereospecific:,acid-promotedbeingantiandbase-promotedbeingsyn.,Hudrlik,PetersonJ.Am.Chem.Soc.1975,97,1464.,.,StabilizedPetersonReagents,-ThestabilizedPetersonreagentsgivepredominantlythemoststabletransolefins(E),.,-Additionalexamples:,.,4.TheTebbeReactionandRelatedTitanium-stabilizedMethylenations(Tebbe反应及与有关稳定化钛试剂的亚甲基化反应）,.,-Toleratesketalandalkenederivatives.ScopedefinedbyEvansandGrubbsJ.Am.Chem.Soc.1980,102,3270.ExtendedtotertiaryamidesbyPineJ.Org.Chem.1985,50,1212.,ForananalogoususeofCp2TiMe2:PetasisJ.Am.Chem.Soc.1990,112,6392.,.,5.Sulphoxide-sulphenaterearragement:Synthesisofallylalcohols(亚砜-次磺酸酯重排：烯丙醇类化合物的合成),Combinedwithalkylationofsulphoxidesthereactionprovidesaversatilesynthesisofdi-andtri-substitutedallylicalcohols,EvansandAndrews,Acc.Chem.Res.,1974,7,147,.,-alkylationofallylicalcohlos,Example1,Example2,.,6.Alkenesfromsulphones(由砜制备烯烃）,-JuliaOlefination,Review:ComprehensiveOrg.Syn.,Vol.1,792.,-Example:,JuliaTetrahedronLett.1973,4833.,.,Juliadevelopedamorerecent,single-stepvariantthatavoidsthereductiveelimination,JuliaBull.Soc.Chim.,Fr.1993,130,336.,Julia,M.etal.,TetrahedronLett.,1973,4833Kocienski,P.J.etal.,J.Chem.Soc.PerkinI,1978,829.,-Example:,.,-RambergBacklundreaction,Org.React.1977,25,1.,Base,-SO2,NicolaouK.C.etal.,J.AmChem.Soc.,1992,114,7360.BoockmanR.K.etal.,J.AmChem.Soc.,1991,113,9682.AlvarzeE.etal.,J.AmChem.Soc.,1995,117,1437.,.,7.Decarboxylationof-lactones(-内酯的脱羧反应）,ReformatskyReaction,Note:Nostilbenewasformed,Synthesisoftri-ortetrasubsitutedalkenes,Example1,.,FehrC.etal.TetrahedronLett.,1992,33,2465,MolbierW.R.etal.J.Org.Chem.,1995,60,5378,Example2,Example3,.,MulzerJ.,etal.,J.Chem.Soc.Chem.Commun.,1979,52,.,8.Stereoselectivesynthesisoftri-andtetra-substitutedalkenes(三、四取代烯烃的立体选择性合成）,Thefirststepishighlystereoselective.TheR4andthelargerofthegroupsR1andR2areantitoeachother.,EarlyMethod,Cornforth,J.W.etal.,J.Chem.Soc.,1959,112,.,Development,Method1,Corey,E.J.etal.,J.Am.Chem.Soc.,1967,89,4246.,.,Example,(54%;97%E),.,Method2,Example:R=Et,Yield72%,Zweifel,G.etal.,J.Am.Chem.Soc.,1967,89,2754.,.,Zweifel,G.etal.,J.Am.Chem.Soc.,1967,89,5085.,.,9.Oxidativedecarboxylationofcarboxylicacids(羧酸的氧化脱羧反应）,Sheldon,R.A.,etal.,OrganicReactions,1972,19,279.,Jahngen,B.G.E.,J.Org.Chem.,1974,39,1650.,与Dieal-Alder反应结合，是制备环状烯烃的好方法。,Example1,.,TanzawaT.etal.TetrahedronLett.,1992,33,6783,Example2,Example3,.,10.Alkenesfromarylsulphonylhydrazones(由芳基磺酰腙制备烯烃）,KolonkoK.,etal.J.Org.Chem.,1978,43,1404;AdlingtonR.M.,etal.Acc.Chem.Res.,1983,16,55,Mechanism,.,Lesssubstitutedalkene,Example1,Example2,.,11.FragmentationReactions(裂解反应）,X=leavinggroup,e.g.:-OSO2C6H4CH3-p,-OSO2CH3,100%stereospecific,Example,.,.,.,12.OlefinInversionReactions(烯烃构型转换反应）,Deoxygenationofepoxides(withretentionofgeometry),.,Otherexamples,.,13.Srereospecificsynthesisofalkenesfrom1,2-diols(由1,2-二醇立体选择性地合成烯烃）,CoreyWinterOlefinSynthesis,CoreyJ.Am.Chem.Soc.1963,85,2677.CoreyJ.Am.Chem.Soc.1965,87,934.,.,EastwoodAust.J.Chem.1964,17,1392.EastwoodTetrahedronLett.1970,5223.,Burgstahler,BogerTetrahedron1976,32,309.,.,14.3,3-SigmatropicRearrangements,ClaisenandCopeRearrangement,.,Examples,EvansJ.Am.Chem.Soc.1975,97,4765.,BurgstahlerJ.Am.Chem.Soc.1961,83,198.,.,CarnduffJ.Chem.Soc.,Chem.Commun.1967,606.,.,Thio-ClaisenRearrangement,Anadvantageofthethio-Claisenrearrangementisthattheprecursorcanbedeprotonatedandalkylated.,CoreyJ.Am.Chem.Soc.1970,92,5522.YamamotoJ.Am.Chem.Soc.1973,95,2693and4446.,BlockJ.Am.Chem.Soc.1985,107,6731.,.,TheCarrollReaction,CarrollJ.Chem.Soc.1940,704,1266.HartungJ.Chem.Soc.1941,507.CopeJ.Am.Chem.Soc.1943,65,1992.TanabeJ.Am.Chem.Soc.1980,102,862.,.,15.2,3-SigmatropicRearrangements,Review:ComprehensiveOrg.Syn.,Vol.6,pp834,873908.Org.React.1994,46,105209.,-Analogousto3,3-sigmatropicrearrangementexceptitenlistsalocalizedcharge(anion)inplaceofadoublebond.,Examples,JuliaTetrahedronLett.1974,2077.,.,LythgoeJ.Chem.Soc.,Chem.Commun.1972,757.,EvansTetrahedronLett.1973,4691.,.,Amino-ClaisenRearrangement,-Thisreactionoccursbestwhennitrogenisconvertedtotheammoniumsalt.,GilbertTetrahedronLett.1984,25,2303.StilleJ.Org.Chem.1991,56,5578.,NakaiChem.Lett.1990,2069.,.,SatoJ.Am.Chem.Soc.1990,112,1999.,.,II.OlefinSynthesisExemplifiedwithJuvenileHormone,(保幼激素的合成）,JuvenileHormone（HJ),1.TrostSynthesis:J.Am.Chem.Soc.1967,89,5292.2.SyntexSynthesis:J.Am.Chem.Soc.1968,90,6224.3.CoreySynthesis:J.Am.Chem.Soc.1968,90,5618.4.JohnsonSynthesis:J.Am.Chem.Soc.1968,90,6225.5.CoreySynthesis:J.Am.Chem.Soc.1970,92,6635,6636,6637.6.JohnsonSynthesis:J.Am.Chem.Soc.1970,92,4463.7.StotterKondoSynthesis:J.Am.Chem.Soc.1973,95,4444.J.Chem.Soc.,Chem.Commun.1972,1311.8.StillSynthesis:TetrahedronLett.1979,593.9.OtherSyntheses:,.,(1).TrostSynthesis,WadsworthHornerEmmonsReaction,.,Stereoselectivity-notmuchdifferencebetweenMeandH(secondatomstericeffect)-bothisomersobtainedfromtheWadsworthHornerEmmonsreaction(Modernimprovementsnowavailable),RetrosyntheticAnalysis-repeatingsubunitsrecognized-repeatingreactionsutilized,J.Am.Chem.Soc.1967,89,5292.,.,(2).SyntexSynthesis,.,J.Am.Chem.Soc.1968,90,6224.,RobinsonAnnulationAlkylationDiastereoselectivityDirectedEpoxidationReactionFragmentationReaction,SelectiveReduction-saturatedvs.a,b-unsaturatedcarbonyl-ringstrainassociatedwith5-memberedringcarbonylreleasedonreduction-attackfromleasthinderedface,THPProtectingGroup-ifRgroupcontainschiralcenters,diastereomersresult-removedbymildacid,.,ThermodynamicEnolate-severe1,3-diaxialinteractioninchair-likeT.S.axialalkylation-nostericincumberancetoaxialalkylationonleasthinderedfaceoftwistboatT.S.,LiAlH(OtBu)3Reduction-largereagent,usuallyequatorialHdelivery-1,2-interaction(torsionalstrain)relativelyinvarianttoNusize-1,3-stericinteractionhighlydependentonNusize-duetoabsenceofaxialC(3)H,largereagentnowgivesaxialdelivery,.,Epoxidation-inEt2O,coordinationofperacidtosolventgivesdeliveryfromtheleasthindereda-face-inCH2Cl2,H-bondingofOHtoperacidprovidesdeliverytothelessaccessibleb-face-TeranishiJ.Am.Chem.Soc.1979,101,159.,FragmentationReaction-utilizedtocontrolC=Cbondstereochemistry-transperiplanarorientationofbreakingbonds-dictatesZolefingeometryinproduct,.,3.CoreySynthesis,.,DissolvingMetalReductionsCyclicPrecursorstoTrisubstitutedOlefinsOxidativeCleavageofEnolEthersLiAlH4ReductionofPropargylAlcoholsCuprateCouplingReactionsAllylicAlcoholOxidation,J.Am.Chem.Soc.1968,90,5618.,StereospecificSynthesisofTrisubstitutedOlefins,.,MnO2Oxidation-mildoxidationofallylicalcohols-direct,mildmethodforoxidationtoamethylester,Epoxidation-selective-inpolarsolventthemoleculefoldsupsuchthattheterminalC=Cismoreaccessible,.,4.JohnsonSynthesis:,Trimethylpyridine,.,J.Am.Chem.Soc.1968,90,6225.,.,5.CoreySynthesis:J.Am.Chem.Soc.1970,92,6635,6636.,.,1,5-HShift,DiimideReduction,-lesssubstitutedC=Creducedmorerapidly-generatedin-situ,.,6.JohnsonSynthesis:J.Am.Chem.Soc.1970,92,4463.,.,OlefinicKetalClaisenReaction-selectivitydependenton1,3-interactioninchair-likeT.S.-secondClaisenmoreselectiveduetolargerRgroupvs.CO2Me,.,7.StotterKondoSynthesis:,J.Am.Chem.Soc.1973,95,4444.J.Chem.Soc.,Chem.Commun.1972,1311.,.,.,8.StillSynthesis:,TetrahedronLett.1979,593.,2,3-SigmatropicRearrangement,.,.,Chapter4ConversionofFunctionalGroups,.,1.AdditionofCarbon-CarbonDoubleBonds,.,2.HalogenationofAlcohols,GeneralMethods,.,Org.Lett.,2002,4(4),553-555,TCT/DMFMethod,Development,2,4,6-trichloro1,3,5triazine,TCT,.,Table1.ConversionofAliphaticAlcoholsintotheCorrespondingAlkylHalides,aForcompleteconversionofthealcohol.bThecorrespondingchlorideisformedalso.,.,Table2.ConversionofDiolsandUnsaturatedand-aminoAlcoholsintotheCorrespondingAlkylHalides,aForcompleteconversionofthealcohol.bThecorrespondingchlorideisformedalso.,.,Mechanism,.,Me3SiCl,该方法对苄醇、伯醇、烯丙醇、叔醇，室温下反应迅速，收率高。,J.Org.Chem.1995,60,2638,.,3.FormationofAmines,GeneralMethods,.,与氮烯有关的重排反应,.,Synthesisprimaryamine,GabrielSynthesis,Harshhydrolysisconditions,Improvement,Synthesis,1990,8,735;1995,7,756Synlett,1996,2,179;Synth.Commun.,1999,29,2685,.,SynthesisofArylaminesfromaminationofArylHalides,Development,.,EarlyPalladium-CatalyzedAmination,该反应仅限于仲胺与电中性的卤代苯。,.,要求等当量的有机钯催化剂。,.,J.Am.Chem.Soc.,1994,116,5969-5970P.Patt,Hartiget.al.,发现Pd可循环使用,从1985到1994近10年没有关于Pd催化胺化反应的报道。,存在的问题：1）要将胺变成锡胺化物；2）不适应于伯胺；3）反应速度较慢；4）催化剂用量较大。,.,InitialTin-freeAminationofArX,HartwigandBuchwald,Angew.Chem.Int.Edu.,1995,34,1348-1350;TetrahedronLett.1995,36,3609,.,RoomTemperatureCatalyticAminationofArylIodides,J.Org.Chem.1997,62,6066-6068,JohnP.WolfeandStephenL.Buchwald*DepartmentofChemistry,MassachusettsInstituteofTechnology,Cambridge,Massachusetts02139,.,.,Table2.RoomTemperatureCatalyticAminationofArylIodides,.,Table2.Continued,.,AHighlyActiveCatalystforPalladium-CatalyzedCross-CouplingReactions:Room-TemperatureSuzukiCouplingsandAminationofUnactivatedArylChloridesDavidW.Old,JohnP.Wolfe,andStephenL.Buchwald*,J.Am.Chem.Soc.1998,120,9722-9723,.,.,AminationReactionsofArylHalideswithNitrogen-ContainingReagentsMediatedbyPalladium/ImidazoliumSaltSystemsGabrielaA.Gra