頻那醇重排課件

頻那醇重排課件頻那醇重排課件previewOverviewHistoryTheGeneralFeaturesSyntheticApplicationspreviewOverviewOverviewTheacyclicandcyclicvicinaldiols,upontreatmentwithcatalyticamountofacid,willundergodehydrationwithconcomitant[1,2]-alkyl-,aryl-orhydrideshifttoaffordketonesoraldehydes.Thisacid-catalyzedtransformationofvicinaldiolsisknownaspinacolrearrangement.OverviewTheacyclicandcyclicMechanismThefirststepoftheprocessisthepronationofoneofthehydroxylgroup,whichresultsinthelossofwatermoleculetogiveacarbocationintermediate.Thisintermediateundergoesa[1,2]-shifttogiveamorestablecarbocationthatuponthelossofprotongivestheproduct.Thepinacolrearrangementwasshowntobeexclusivelyintramolecular,andbothinversionandretentionwereoberservedatthemigratingcenter.MechanismThefirststepoftheHistoryresearchinacetoneL?wigandWeidmann'workFittigandSt?deler'sdisputeFittig'snewobservationTheproblemofrepresentingthestructuresofpinacolandpinacoloneremaindUsingwrongconventinalatomicweightHistoryresearchinacetoneL?wiHistoryWilhelmRudolphFittig(6December1835–19November1910)wasaGermanchemist.

Fittig'sworkonpinnacolrearrangementwashisindependentresearch.Itgrowoutofaninterestinareadilyavaiblesubstance,acetone.HistoryWilhelmRudolphFittig(HistoryJustusFreiherrvonLiebig(12May1803–18April1873)wasaGermanchemistwhomademajorcontributionstoagriculturalandbiologicalchemistry.DuringtheyearsbeforeandaftertheLiebiganalysis,severalchemistsmadeattemptstodeterminethechemicalnatureofacetone.HistoryJustusFreiherrvonLieHistoryCarlL?wig:Germanchemist.(March17,1803-March27,1890).L?wigwasProfessoratHeidelberg,Zurich,andBreslau.Hetaughtfornearly60years,discoveredmanybrominecompounds,andfoundedtheSilesianchemicalindustry.L?wigandWeidmannwereinvestigatingthethen-popularideathatacetonewasanalcoholanddecidedtotestitbytreatmentofitwithmentallicpotassium,hopingtoobtainasalt.HistoryCarlL?wig:GermanHistoryInstead,theyfoundthatthemainproductsweremesityloxideandphorone(resultingfromwhatwenowwouldcallanaldolcondensation).Thesearethesameproductsthathadpreviouslybeenobservedfromtheactionofpotassiumhydroxideonacetone.L?wig,C.;Weidmann,S.J.Prakt.Chem.1840,21,64.HistoryInstead,theyfoundthaHistoryFittigstartedoutwiththemodestobjectiveofrepeatingtheL?wig-Weidmannexperimentwithsodiuminsteadofpotassium.Superficially,onemighthaveexpectedthetwoexperimentgavetogivesimilarresults,butthatwasnottobethecase.TobringLiebig'sdeterminationoftheatomiccompositionofacetoneintoharmonywiththeconventionalsystemofatomicweights,FittighadtoconvertLiebig'sformulaC3H6OintotheincorrectconvertionalformulaC3H3O.Sohisprojectwasinimmediatetrouble.Berson,J.A.Angew.Chem.2002,41,24.HistoryFittigstartedoutwithHistoryFittig'sintentiontomakeandalkylateasodiumsaltfromacetonemighthavebeenconsidereddubiousinviewofthefailureofL?wigandWeidmannwiththepotassiumenolate.However,hedidfindanunexpectedandmostinterestingsubstance,whichheisolatedaslarge,tablet-shapedcrystalsandwhichhecalled"paraceton".Thatwasthesubstancelaterwouldbecalled"pinacol".Fittig'snameforthisproduct,paraceton,camefromhisbeliefthatitwasahydrateofadimerofacetone.Fittigfoundthatheatingpinacolwithaqueoussulfuricacidorhydrochloricacidgaverisetoanewsubstancenowknownaspinacolone.HistoryFittig'sintentiontomHistoryCharlesFriedel(12March1832–20April1899)wasaFrenchchemistandmineralogist.HistoryCharlesFriedel(12MarHistoryIn1869,Friedelpublishedthatpinacolwastetramethyleneglycol(2).Friedel,C.Ann.Chim.Phys.Ser.41869,16,310.HistoryIn1869,FriedelpublisHistoryThefogsurroundingallthischemistrywasfinallydisspelledbytwobrilliantpaperofAlexanderButlerovofSt.Petersburg.AlexanderMikhaylovichButlerov(Алекса?ндрМиха?йловичБу?тлеров;September15,1828–August17,1886)wasaRussianchemist.HistoryThefogsurroundingallHistoryButlerov,A.JustusLiebigsAnn.Chem.1874,174,125.Butlerov,A.JustusLiebigsAnn.Chem.1873,170,151.Butlerov,A.JustusLiebigsAnn.Chem.1873,170,162.HistoryButlerov,A.JustusLieTheGeneralFeatures1)virtuallyanycyclicoracyclicvicinalglycolcanundergotherearrangement,and,dependingonthesubstitutionpattern,aldehydesand/orketonesareformed;2)whenallfoursubstituentsareidentical,therearrangementyieldsasingleproduct;3)whenthefoursubstituentsarenotidentical,productmixturesareformed;Kürti,L.;Czakó,B.StrategicApplicationsOfNamedReactionsInOrganicSynthesis[A].ElsevierAcademicPress,2005,350-351.TheGeneralFeatures1)virtualTheGeneralFeatures4)theproductisusuallyformedviathemoststablecarbocationintermediatewhentheglycolsubstrateisunsymmetrical;5)thereactioncanbehighlyregioselectiveandtheregioselectivityisdeterminedbytherelativemigratoryaptitudesofthesubstituentsattachedtothecarbonadjacentthecarbocationcenter;6)thesubstituentthatisabletostabilizeapositivechargebetter(betterelectrondonor)tendstomigratepreferentially;Kürti,L.;Czakó,B.StrategicApplicationsOfNamedReactionsInOrganicSynthesis[A].ElsevierAcademicPress,2005,350-351.TheGeneralFeatures4)theproTheGeneralFeatures7)therelativemigratoryaptitudesare:aryl~H~vinyl(alkenyl)>t-Bu>>cyclopropyl>2°alkyl>1°alkyl;8)thepinacolrearrangementcanalsobestereoselectiveespeciallywhencomplexcyclicvicinaldiolsareinvolved;9)cyclicsystemsmayrearrangeviabothring-expansionandring-contractionandthecourseoftherearrangementisstronglyinfluencedbytheringsize;Kürti,L.;Czakó,B.StrategicApplicationsOfNamedReactionsInOrganicSynthesis[A].ElsevierAcademicPress,2005,350-351.TheGeneralFeatures7)therTheGeneralFeatures10)mostoftenacoldaqueoussolutionofsulfuricacid(25%H2SO4)isusedtoeffecttherearrangement;however,otheracidssuchasperchloricacidandphosphoricacidhavealsobeenutilized;11)besidesproticacids,Lewisacids(e.g.,BF3·OEt,TMSOTf)arealsoused.Kürti,L.;Czakó,B.StrategicApplicationsOfNamedReactionsInOrganicSynthesis[A].ElsevierAcademicPress,2005,350-351.TheGeneralFeatures10)mostoTheGeneralFeaturesTheGeneralFeaturesTheGeneralFeaturesTheGeneralFeaturesTheGeneralFeatures1)itisgenerallynoteasytopreparecomplexvicinaldiols;2)inthecaseofunsymmetricalsubstrates,theregioselectiveformationofonlyonecarbocationisusuallynottrivial,soproductmixturesareobtained;3)sidereactionssuchasβ-eliminationsyieldingdienesandallylicalcoholsareoftenobserved;4)theintermediatecarbocationsmayundergoequilibration;Kürti,L.;Czakó,B.StrategicApplicationsOfNamedReactionsInOrganicSynthesis[A].ElsevierAcademicPress,2005,350-351.TheGeneralFeatures1)itisgTheGeneralFeatures5)variousconformationaleffectsandneighboringgroupparticipationincyclicsystemsarecomplicatingfactors.Whenoneofthehydroxylgroupsisconvertedtoagoodleavinggroup,theregioselectivegenerationofthecarbocationintermediateispossible.Similarlyselectivegenerationofcarbocationscanberealizedwhen2-heterosubstitutedalcohols(e.g.,halohydrins,2-aminoalcohols,2-hydroxysulfides,etc.)areusedassubstrates.Thepinacol-typerearrangementofthesecompoundsisreferredtoasthesemipinacolrearrangement,atermfirstcoinedbyM.Tiffeneau.Owingtoitspredictabilityandthemildreactionconditions,thesemipinacolrearrangementisalmostexclusivelyutilizedincomplexmoleculesynthesis.Kürti,L.;Czakó,B.StrategicApplicationsOfNamedReactionsInOrganicSynthesis[A].ElsevierAcademicPress,2005,350-351.TheGeneralFeatures5)variousSyntheticApplicationsSyntheticApplicationsSyntheticApplicationsXu,W.;Wu,S.;Zhou,L.Org.Lett.2013,Vol.15,No.8SyntheticApplicationsXu,W.;WSyntheticApplicationsXu,W.;Wu,S.;Zhou,L.Org.Lett.2013,Vol.15,No.8SyntheticApplicationsXu,W.;W頻那醇重排課件頻那醇重排課件previewOverviewHistoryTheGeneralFeaturesSyntheticApplicationspreviewOverviewOverviewTheacyclicandcyclicvicinaldiols,upontreatmentwithcatalyticamountofacid,willundergodehydrationwithconcomitant[1,2]-alkyl-,aryl-orhydrideshifttoaffordketonesoraldehydes.Thisacid-catalyzedtransformationofvicinaldiolsisknownaspinacolrearrangement.OverviewTheacyclicandcyclicMechanismThefirststepoftheprocessisthepronationofoneofthehydroxylgroup,whichresultsinthelossofwatermoleculetogiveacarbocationintermediate.Thisintermediateundergoesa[1,2]-shifttogiveamorestablecarbocationthatuponthelossofprotongivestheproduct.Thepinacolrearrangementwasshowntobeexclusivelyintramolecular,andbothinversionandretentionwereoberservedatthemigratingcenter.MechanismThefirststepoftheHistoryresearchinacetoneL?wigandWeidmann'workFittigandSt?deler'sdisputeFittig'snewobservationTheproblemofrepresentingthestructuresofpinacolandpinacoloneremaindUsingwrongconventinalatomicweightHistoryresearchinacetoneL?wiHistoryWilhelmRudolphFittig(6December1835–19November1910)wasaGermanchemist.

Fittig'sworkonpinnacolrearrangementwashisindependentresearch.Itgrowoutofaninterestinareadilyavaiblesubstance,acetone.HistoryWilhelmRudolphFittig(HistoryJustusFreiherrvonLiebig(12May1803–18April1873)wasaGermanchemistwhomademajorcontributionstoagriculturalandbiologicalchemistry.DuringtheyearsbeforeandaftertheLiebiganalysis,severalchemistsmadeattemptstodeterminethechemicalnatureofacetone.HistoryJustusFreiherrvonLieHistoryCarlL?wig:Germanchemist.(March17,1803-March27,1890).L?wigwasProfessoratHeidelberg,Zurich,andBreslau.Hetaughtfornearly60years,discoveredmanybrominecompounds,andfoundedtheSilesianchemicalindustry.L?wigandWeidmannwereinvestigatingthethen-popularideathatacetonewasanalcoholanddecidedtotestitbytreatmentofitwithmentallicpotassium,hopingtoobtainasalt.HistoryCarlL?wig:GermanHistoryInstead,theyfoundthatthemainproductsweremesityloxideandphorone(resultingfromwhatwenowwouldcallanaldolcondensation).Thesearethesameproductsthathadpreviouslybeenobservedfromtheactionofpotassiumhydroxideonacetone.L?wig,C.;Weidmann,S.J.Prakt.Chem.1840,21,64.HistoryInstead,theyfoundthaHistoryFittigstartedoutwiththemodestobjectiveofrepeatingtheL?wig-Weidmannexperimentwithsodiuminsteadofpotassium.Superficially,onemighthaveexpectedthetwoexperimentgavetogivesimilarresults,butthatwasnottobethecase.TobringLiebig'sdeterminationoftheatomiccompositionofacetoneintoharmonywiththeconventionalsystemofatomicweights,FittighadtoconvertLiebig'sformulaC3H6OintotheincorrectconvertionalformulaC3H3O.Sohisprojectwasinimmediatetrouble.Berson,J.A.Angew.Chem.2002,41,24.HistoryFittigstartedoutwithHistoryFittig'sintentiontomakeandalkylateasodiumsaltfromacetonemighthavebeenconsidereddubiousinviewofthefailureofL?wigandWeidmannwiththepotassiumenolate.However,hedidfindanunexpectedandmostinterestingsubstance,whichheisolatedaslarge,tablet-shapedcrystalsandwhichhecalled"paraceton".Thatwasthesubstancelaterwouldbecalled"pinacol".Fittig'snameforthisproduct,paraceton,camefromhisbeliefthatitwasahydrateofadimerofacetone.Fittigfoundthatheatingpinacolwithaqueoussulfuricacidorhydrochloricacidgaverisetoanewsubstancenowknownaspinacolone.HistoryFittig'sintentiontomHistoryCharlesFriedel(12March1832–20April1899)wasaFrenchchemistandmineralogist.HistoryCharlesFriedel(12MarHistoryIn1869,Friedelpublishedthatpinacolwastetramethyleneglycol(2).Friedel,C.Ann.Chim.Phys.Ser.41869,16,310.HistoryIn1869,FriedelpublisHistoryThefogsurroundingallthischemistrywasfinallydisspelledbytwobrilliantpaperofAlexanderButlerovofSt.Petersburg.AlexanderMikhaylovichButlerov(Алекса?ндрМиха?йловичБу?тлеров;September15,1828–August17,1886)wasaRussianchemist.HistoryThefogsurroundingallHistoryButlerov,A.JustusLiebigsAnn.Chem.1874,174,125.Butlerov,A.JustusLiebigsAnn.Chem.1873,170,151.Butlerov,A.JustusLiebigsAnn.Chem.1873,170,162.HistoryButlerov,A.JustusLieTheGeneralFeatures1)virtuallyanycyclicoracyclicvicinalglycolcanundergotherearrangement,and,dependingonthesubstitutionpattern,aldehydesand/orketonesareformed;2)whenallfoursubstituentsareidentical,therearrangementyieldsasingleproduct;3)whenthefoursubstituentsarenotidentical,productmixturesareformed;Kürti,L.;Czakó,B.StrategicApplicationsOfNamedReactionsInOrganicSynthesis[A].ElsevierAcademicPress,2005,350-351.TheGeneralFeatures1)virtualTheGeneralFeatures4)theproductisusuallyformedviathemoststablecarbocationintermediatewhentheglycolsubstrateisunsymmetrical;5)thereactioncanbehighlyregioselectiveandtheregioselectivityisdeterminedbytherelativemigratoryaptitudesofthesubstituentsattachedtothecarbonadjacentthecarbocationcenter;6)thesubstituentthatisabletostabilizeapositivechargebetter(betterelectrondonor)tendstomigratepreferentially;Kürti,L.;Czakó,B.StrategicApplicationsOfNamedReactionsInOrganicSynthesis[A].ElsevierAcademicPress,2005,350-351.TheGeneralFeatures4)theproTheGeneralFeatures7)therelativemigratoryaptitudesare:aryl~H~vinyl(alkenyl)>t-Bu>>cyclopropyl>2°alkyl>1°alkyl;8)thepinacolrearrangementcanalsobestereoselectiveespeciallywhencomplexcyclicvicinaldiolsareinvolved;9)cyclicsystemsmayrearrangeviabothring-expansionandring-contractionandthecourseoftherearrangementisstronglyinfluencedbytheringsize;Kürti,L.;Czakó,B.StrategicApplicationsOfNamedReactionsInOrganicSynthesis[A].ElsevierAcademicPress,2005,350-351.TheGeneralFeatures7)therTheGeneralFeatures10)mostoftenacoldaqueoussolutionofsulfuricacid(25%H2SO4)isusedtoeffecttherearrangement;however,otheracidssuchasperchloricacidandphosphoricacidhavealsobeenutilized;11)besidesproticacids,Lewisacids(e.g.,BF3·OEt,TMSOTf)arealsoused.Kürti,L.;Czakó,B.StrategicApplicationsOfNamedReactionsInOrganicSynthesis[A].ElsevierAcademicPress,2005,350-351.TheGeneralFeatures10)mostoTheGeneralFeaturesTheGeneralFeaturesTheGeneralFeaturesTheGeneralFeaturesTheGeneralFeatures1)itisgen