手性合成要点绪论

PrinciplesandApplicationsofAsymmetricSynthesis

CHAPTER1Introduction

Theuniverseisdissymmetrical;forifthewholeofthebodieswhichcomposethesolarsystemwereplacedbeforeaglassmovingwiththeirindividualmovements,theimageintheglasscouldnotbesuperimposedonreality....Lifeisdominatedbydissymmetricalactions.Icanforeseethatalllivingspeciesareprimordially,intheirstructure,intheirexternalforms,functionsofcosmicdissymmetry.ÐLouisPasteurBriefhistory

1801,HauÈy:quartzcrystalsexhibitedhemihedralphenomena;1809,Malus,:quartzcrystalscouldinducethepolarizationoflight;1812,Biot:Rightandleftformsofquartzcrystalsrotatedtheplaneofthepolarizedlightinindifferentdirections.1815.Biot:differencesbetweentherotationcausedbyquartzcrystalsandthatcausedbythesolutionsoforganiccompounds1822,JohnHerschel:therewasacorrelationbetweenhemihedralismandopticalrotation.1846-1848,Pasteur:therotationofpolarizedlightcausedbydifferenttartaricacidsaltcrystalswasthepropertyofchiralmolecules.1874.independentpublicationsbyJ.H.van'tHoffandJ.A.LeBeldatedtheactualbirthofstereochemistry1.1

THESIGNIFICANCEOFCHIRALITYANDSTEREOISOMEICDISCRIMINATIONAnobjectischiralifitcannotbesuperimposedonitsmirrorimage.Insuchacase,therearetwopossibleformsofthesameobject,whicharecalledenantiomers,andthusthesetwoformsaresaidtobeenantiomericwitheachother.Enantiomers:haveidenticalchemicalandphysicalpropertiesintheabsenceofanexternalchiralinfuence.opticalactivity:Thepropertyofrotatingplane-polarizedlight.thetwoenantiomersofachiralmoleculerotatetheplaneofpolarizedlighttoadegreethatisequalinmagnitude,butoppositeindirection.dextrorotatorymolecule:theenantiomerthatrotatespolarizedlightinaclockwisedirection,indicatedbyaplussign(+)oritalicletter``d''.levorotatory

molecule:theenantiomerwhichrotatespolarizedlightinacounterclockwisedirection,assignedaminussign(-)oritalicletter``l''.stereoisomericdiscriminationisverystrikinginbiologicalsystemsFourdifferentbehaviorsofchiralcompounds:(1)onlyoneenantiomerhasthedesiredbiologicalactivity,andtheotheronedoesnotshowsignificantbioactivity;(2)bothenantiomershaveidenticalornearlyidenticalbioactivity;(3)theenantiomershavequantitativelydifferentactivity;(4)thetwoenantiomershavedifferentkindsofbiologicalactivity.Example:l-DOPA

.forParkinson'sdiseaseasymmetry(orchirality)playsanimportantroleinlifesciences.Otherexamples:1.2ASYMMETRYasymmetrymaybecreatedbyoneofthefollowingthreeconditions:CompoundswithanasymmetriccarbonatomCompoundswithanotherquaternarycovalentchiralcenterbindingtofourdifferentgroupsthatoccupythefourcornersofatetrahedron:Si,Ge,N(inquaternarysaltsorN-oxides)Mn,Cu,BiandZn--whenintetrahedralcoordination.Compoundswithtrivalentasymmetricatoms:1.2.1.NomenclatureFischer'sConvention:R-CHX-R’IftheXgroup(usually±OH,±NH2,orahalogen)isontherightside,therelativeconfigurationisdesignatedD;otherwisetheconfigurationisdesignatedL.TheCahn-Ingold-PrelogConvention.Inthenomenclaturesystem,atomsorgroupsbondedtothechiralcenterareprioritizedfirst,basedonthesequencerules.(1)Anatomhavingahigheratomicnumberhaspriorityoveronewithaloweratomicnumber;forisotopicatoms,theisotopewithahighermassprecedestheonewiththelowermass.(2)Iftwoormoreoftheatomsdirectlybondedtotheasymmetricatomareidentical,theatomsattachedtothemwillbecompared,accordingtothesamesequencerule.Thus,ifthereisnoheteroatominvolved,alkylgroupscanbesequencedastertiary>secondary>primary.Whentwogroupshavedifferentsubstituents,thesubstituentbearingthehighestatomicnumberoneachgroupmustbecomparedfirst.Thesequencedecisionforthesegroupswillbemadebasedonthesequenceofthesubstituents,andtheonecontainingpriorsubstituentshasahigherprecedence.Asimilarruleisapplicableinthecaseofgroupswithheteroatoms.Formultiplebonds,adoublyortriplybondedatomisduplicatedortriplicatedwiththeatomtowhichitisconnected.

(4)Forvinylgroups,agrouphavingthe(Z)-configurationprecedesthesamegrouphavingthe(E)-configuration,andan(R)-grouphasprecedenceoveran(S)-groupforpseudochiralcenters..CentralChirality.AxialChirality.PlanarChirality.HelicalChirality.OctahedralStructures.PseudochiralCenters.Differenttypesaccordingtospatialorientation.1.3DETERMININGENANTIOMERCOMPOSITIONenantiomerexcessdiastereomerexcess1.3.1MeasuringSpecificRotationListhepathlengthofcell(dm);cisconcentration(g/100ml);DistheDlineofsodium,thewavelengthoflightusedformeasurement(5983AÊ);and20isthetemperatureindegrees(Celsius).1.3.2TheNuclearMagneticResonanceMethodNuclearMagneticResonanceSpectroscopyMeasuredinaChiralSolventorwithaChiralSolvatingAgent.NuclearMagneticResonancewithaChiralChemicalShiftReagent.Chiral

DerivatizingAgentsforNuclearMagneticResonanceAnalysis.Variouschiral

derivatizingagents1.3.4ChromatographicMethodsUsingChiralColumns:

GasChromatography.Themethodisbasedontheprinciplethatmolecularassociationbetweenthechiralstationaryphaseandthesamplemayleadtosomechiralrecognitionandsufficientresolutionoftheenantiomers.LiquidC