Transcription of RETROSYNTHETIC ANALYSIS
1 RETROSYNTHETICANALYSIS1 RetrosyntheticAnalysis and Synthetic PlanningDefinitions2 Retrosyntheticanalysisisatechniqueforpla nningasynthesis,especiallyofcomplexorgan icmolecules,wherebythecomplextargetmolec ule(TM)isreducedintoasequenceofprogressi velysimplerstructures(retrons)alongapath waywhichultimatelyleadstotheidentificati onofasimpleorcommerciallyavailablestarti ngmaterial(SM) :16 AMSynthetic PlanningLinear Synthesis3 Inlinearsynthesis, :16 AMSynthetic PlanningConvergent Synthesis4 Inconvergentsynthesis, 5 ConsidertheretrosyntheticanalysisofMusca lure,thepheromoneofthedomestichousefly, :16 AMRetrosyntheticAnalysis :16 AMSynthetic ,butmostimportantly, :16 AMSynthetic Planning8 Comparingthetwosyntheticpathwaysshowstha twhiletheWittigrouteisconvergent, Planning9 Retrosyntheticanalysisandsyntheticplanni ngrequirestraining(knowledgeofchemistry) andexperience(practicalapplicationofthec hemistry).
2 Thewidersomeone'sknowledgebaseisinorgani cchemistry, ,ifpossible, :16 AMTerminology of RetrosyntheticAnalysisDisconnection10 Duringretrosyntheticanalysisthetargetmol eculeissystematicallybrokendownbyacombin ationoffunctionalgroupinterconversion(FG I) , of RetrosyntheticAnalysis11 Adisconnectionisrepresentedbyawavy( )linethroughthebondbeingdisconnected,. Aretrosyntheticarrow( )representsgoingfromthetargetmolecule backwards tosimplermolecules(retrons). Asyntheticarrow() :16 AMTerminology of RetrosyntheticAnalysisFunctional Group Interconversion12 Functionalgroupinterconversion(FGI) , 'toffermuchgaintoasynthesis, :16 (imaginary) :16 AMTerminology of RetrosyntheticAnalysis14 Asynthonisanidealizedfragmentorspecies( +orCH3-) ( ) :16 AMStrategies in Synthetic Planning15(a)Striveforsuccessandgoodcost managementInplanningasynthesisgenerateal argenumberofretrosyntheticpathwaystothet argetmolecule:Examinetheseretrosynthetic pathwaystoidentifyamongthemanoptimalsynt heticrouteforwhichreagentsarereadilyavai lableandinexpensive.
3 (b)ConvergentvsLinearsynthesisWhenconsid eringadisconnectionintheretrosynthetican alysisofacomplextargetmolecule,try(ifpos sible) (c)Aimfordisconnectionsthatleadtothegrea testsimplificationofthetargetmoleculeGiv enachoiceofpossibledisconnections, :16 AMStrategies in Synthetic PlanningStrategies in Synthetic Planning17(d) :16 AMStrategies in Synthetic Planning18(e) :10:16 AMStrategies in Synthetic PlanningSynthesis of the Epoxy Alcohol1910:16 AMBasedontheprecedingretrosyntheticplans ,theepoxyalcoholscanbesynthesizedasshown below:Strategies in Synthetic Planning20(f)Duringretrosyntheticanalysi sintroduceadditionalfunctionalgroups,ifn ecessary,todirectbondformation:Functiona lgroupaddition(FGA)strategyThefunctional groupadditionstrategyinretrosyntheticana lysisinvolvesintroducingadditionalfuncti onalgroupsatstrategiclocationsinaretron, ifnecessary, in Synthetic PlanningFunctional Group Addition Strategy21 Forexample,introductionofadoublebondinac yclohexanetargetmoleculemayhelpkeyadisco nnectionbasedonaDielsAlderreaction.
4 16 AMStrategies in Synthetic Planning22(g)Useprotectinggroupsifinevit ableGiventhattheuseofprotectinggroupsadd stothenumberofstepsofasynthesis, :16 AMSample Retrosynthesesand SynthesesRetrosynthetic ANALYSIS of Tamariscol2310:16 :Sample Retrosynthesesand SynthesesSynthesis of Tamariscolbased on RCM2410:16 AMThesynthesisoftamariscolbasedonringclo singmetathesisishighlightedbelow:Sample Retrosynthesesand SynthesesSample Problems2510:16 AM(1)Proposeretrosyntheticandsyntheticsc hemesforbombykol,apheromonereleasedbythe femalesilkwormtoattractmales.(2) in Synthesis of Natural Products26(a)TotalsynthesisTotalsynthesi sreferstothesynthesisofcomplexnaturalcom poundsfromsimplecommonstartingmaterialst hatarecommerciallyavailable.
5 (b) :16 AMTerminology in Synthesis of Natural Products27(c)FormalsynthesisFormalsynthe sisreferstotheindependentsynthesisofanad vancedprecursorofanaturalproduct, :16 AMCAT 2 organic SYNTHESIS28 THURSDAY, 6 THAPRIL AMG1410:16 AM
