上海有机所合成讲义第6讲PPT演示课件

第二节取代反应,1,F-CAlkylations,Varioussidereactionssuchasisomerization,fragmentationanddealkylationtogetherwithside-chainandpositinalrearrangementsoftenoccurred.,2,Sugitaet.al.:ByadditionadditivesCuCl2orCu2Cl2ordeclaintoobtainhighregioselectivity.,3,Ritterreaction,Tertiaryalcoholstendtoreactwithoutrearrangementwhilesecondaryalcoholsareliabletodoso.Primeayalcoholsnormallyfailtoreactwithnitrilesexceptthebenzylicexamples.,4,eitheralcoholisomergavemainlytheamineproductproducedbyaxialattackonthecarbon.,Stereo-selective,5,1)硅烷还原反应,2)催化氢化,脱水ROOCCF3,第三节还原反应,6,3)单电子还原,7,4)自由基还原,-Permitthedeoxygenationofmosttypesofalcoholsandthemonodeoxygenationof1,2and1,3-diols,theseprocessesarelimitedonlybythoseside-reactions(intramolecularcyclizationsorfragmentations)ofcarbonradicalswhichcansuccessfullycompetewithH-abstractionfromanefficientdonor(R3SnH),andfrequentlyprovidethemethodofchoicefordeoxygenationinpolyfunctionalizedsystemsbearinggroupssensitivetohydrideordissolvingmetalreagents.Review:Hartwig,W.,Tetrahedron,1983,39,2609;Barton,D.H.R.andMotherwell,W.B.,PureAppl.Chem.,1981,53,15.,8,Wagner-Meerweinrearrangement,第四节其他反应,9,Pinacolrearrangement,各类邻二醇不对称取代的二醇中，生成更稳定碳正离子的碳上的羟基更容易质子化后离去；碳正离子相邻碳上能够稳定碳正离子的基团优先迁移；迁移基团与离去基团处于反位更易于重排。,10,加成反应,11,合成参见：,ViaenereactionComprehensiveOrganicSynthesis,2,538;ViaoxidativecleavageofalkenesComprehensiveOrganicSynthesis,7,541;ViacarboxylicacidsComprehensiveOrganicSynthesis,8,235;ViaenantiomericreductionofcarbonylcompoundsComprehensiveOrganicSynthesis,8,185;ViaepoxidereductionComprehensiveOrganicSynthesis,8,871;ViahydrogentransferComprehensiveOrganicSynthesis,8,110;ViametalhydrideComprehensiveOrganicSynthesis,8,1-22;ViaorganoboranesComprehensiveOrganicSynthesis,3,793;ViaorganoceriumcompoundsComprehensiveOrganicSynthesis,1,231;ViareductionofhydroperoxidesComprehensiveOrganicSynthesis,8,396;ViasubstitutionprocessesComprehensiveOrganicSynthesis,6,1-28;,12,第五章羰基化合物的反应,13,第一节Enolate的化学,参考文献：,FormationofEnolates:ComprehensiveOrg.Syn.,Vol.2,99.EnolateAlkylations:ComprehensiveOrg.Syn.,Vol.3,1.AldolCondensation:ComprehensiveOrg.Syn.,Vol.2,133,181and239.ReformatskyReaction:ComprehensiveOrg.Syn.,Vol.2,277.AcylationofEnolates:ComprehensiveOrg.Syn.,Vol.2,796.EnolEthers:ComprehensiveOrg.Syn.,Vol.2,595and629.Metalloenamines:ComprehensiveOrg.Syn.,Vol.2,475.Hydrazones:ComprehensiveOrg.Syn.,Vol.2,503.,14,a.EstimationofpKa,-anincreaseinacidityofHresultsinafasterdeprotonation(kineticeffect)aswellasastabilizationofanionformed(thermodynamiceffect).,5-1-1一些基本问题,15,16,b.Ketone-EnolTautomerism,17,18,Ifacompoundhasavinylspacer,thereactivityparallelsthatoftheparentcompound.1,3-CyclohexadioneinitsenolformisavinylogouscarboxylicacidanditexhibitsmanypropertiesofaRCOOH,includinglowpKa,O-alkylation.,19,c.EnolateStructure,-Actuallyexistashigheraggregatesinsolution:dimer-tetramer.-OriginallysuggestedbyHouseJ.Org.Chem.1971,36,2361.-SupportedbyNMRstudies:JackmanTetrahedron1977,33,2737.-ConfirmedbyX-ray:DunitzHelv.Chim.Acta1981,64,2617.,20,21,Useofabasewhichstoichiometricallydeprotonatestheketonecompletely:(i.e.Keq100),5-1-2合成,22,Therefore,agooddeprotonation(essentiallyallketonedeprotonated)Note:needtohavepKadifferenceof2pKaunitstogetKeq=100.,23,-Aggregates:WilliardJ.Org.Chem.1993,58,1.-Otherwidelyusedbases:,24,Reviews:ConiaRec.Chem.Prog.1963,24,43.HouseRec.Chem.Prog.1967,28,99.FlemingChimica1980,34,265.FlemingSynthesis1982,521.FlemingSynthesis1977,509.dAngeloTetrahedron1976,32,2979(Methodsforregiospecificenolategeneration).EvansAsymm.Synthesis,Morrison,Ed.,Vol.3,1.,25,KineticandThermodynamicEnolates,26,RegiospecificEnolateGeneration,Intheabovecase,theD2,3enolatecannotbecleanlyobtaineddirectly,butotherapproachestothishavebeendeveloped.,Representiveenolateselectivities:,27,Enantio-ordiastereoselectiveprotonationofketoneenolates：deprotonation:MajewskiCan.J.Chem.1994,72,1699.SimpkinsTetrahedronLett.1992,33,8141&1989,30,7241.protonation:FehrAngew.Chem.,Int.Ed.Eng.1994,33,1764.,28,CyclicCarbonylCompounds-siteofdeprotonation-enolategeometryfixed,29,IrelandTransitionStateModelforDeprotonationJ.Am.Chem.Soc.1976,98,2868.,30,StereoselectiveEnolateGeneration,31,-ASIDE:GeometryofenolatecanbedeterminedbyClaisenrearrangement:,-Claisenrearrangementknowntoproceedthroughchair-likeT.S.:,32,AcyclicKetones,33,Thermodynamicenolateformation,34,35,AcyclicEsters(Similartoketones):,36,37,OteraSynlett1994,213.,SilylKeteneAcetals,38,AcyclicAmides,39,ForAcyclicKetones,