Felkin规则和Cram规则 不对称诱导Word格式.docx

Felkin规则和Cram规则 不对称诱导Word格式.docx

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如图纽曼投影式所示。

亲核试剂从左侧进攻羰基。

手性碳上的最大基团与羰基碳氧键保持垂直。

基团大小由CPI规则确定。

Felkin规则和Cram规则说的是同一件事，Felkin规则是Cram规则的发展，更准确。

适用条件是C=O的a-C是手型的。

CramI：

如果在C=O的α-C联有三个体积不同的基团，就会造成羰基平面两侧的空间阻碍不同，给亲核试剂进攻羰基创造了空间上的选择性，我们用L、M、S分别表示α-C上体积大、中、小的三个基团，规则如图所示。

CramII：

规则二适用于当α-C上有-OH，-NHR之类的基团从而和羰基氧形成氢键的情况。

本情况下，应该取重叠式构象为最稳构象，亲核试剂从S侧进攻。

Cram法则

Felkin-Ahn 

and 

Chelation 

Control

InFelkin-Ahnmodel,anucleophilecomesfromtheleasthinderedside.ThebestwaytodoFelkin-Ahnmodelistodrawanewmenprojection.Thenhavethenucleophileattackfromthesmallestgroup.

Felkin-Ahnmodelexample:

Here,themodelshowsthatthenucleophilepreferstoattackfromtheleasthinderedside.

ChelationControl:

InChelationControlthereisalwaysalewisbaseorlewisacidispresent.Example:

LewisBasesareOR'

NR2'

orSR'

andlewisacidsareLi+,MgX+,Zn+2.Sincelewisbaseispresentthedoublebondedoxygenandlewisbaseformaringwithlewisacid.

ChelationControlexample:

NextslideshowsthatwhenaLewis-baseorLewis-Acidispresent,ChelationControlgivesthemajorproduct,byformingaringintransitionstateandFelkin-Ahnmodelsfails.

InGeneral:

HowtochoosebetweenFelkin-AhnandChelationControl:

Asymmetricinduction（alsoenantioinduction）instereochemistrydescribesthepreferentialformationinachemicalreactionofoneenantiomerordiastereoisomerovertheotherasaresultoftheinfluenceofachiralfeaturepresentinthesubstrate,reagent,catalystorenvironment.[1]Asymmetricinductionisakeyelementinasymmetricsynthesis.

AsymmetricinductionwasintroducedbyHermannEmilFischerbasedonhisworkoncarbohydrates.[2]Severaltypesofinductionexist.

Internalasymmetricinductionmakesuseofachiralcenterboundtothereactivecenterthroughacovalentbondandremainssoduringthereaction.Thestartingmaterialisoftenderivedfromchiralpoolsynthesis.Inrelayedasymmetricinductionthechiralinformationisintroducedinaseparatestepandremovedagaininaseparatechemicalreaction.Specialsynthonsarecalledchiralauxiliaries.Inexternalasymmetricinductionchiralinformationisintroducedinthetransitionstatethroughacatalystofchiralligand.Thismethodofasymmetricsynthesisiseconomicallymostdesirable.

Contents

[hide] 

∙1Carbonyl1,2asymmetricinduction

o1.1Cram'

srule

o1.2Felkinmodel

o1.3Felkin-Anhmodel

o1.4Anti–Felkinselectivity

∙2Carbonyl1,3asymmetricinduction

o2.1Chelationmodel

o2.2Non-chelationmodel

o2.3Cram–Reetzmodel

o2.4Evansmodel

∙3Carbonyl1,2and1,3asymmetricinduction

∙4Acyclicalkenesasymmetricinduction

∙5Seealso

∙6References

∙7Externallinks

Carbonyl1,2asymmetricinduction[edit]

Severalmodelsexisttodescribechiralinductionatcarbonylcarbonsduringnucleophilicadditions.Thesemodelsarebasedonacombinationofstericandelectronicconsiderationsandareofteninconflictwitheachother.ModelshavebeendevisedbyCram（1952）,Cornforth（1959）,Felkin（1969）andothers.

Cram'

srule[edit]

TheCram'

sruleofasymmetricinductiondevelopedbyDonaldJ.Cramin1952[3]isanearlyconceptrelatingtothepredictionofstereochemistryincertainacyclicsystems.Infulltheruleis:

Incertainnon-catalyticreactionsthatdiastereomerwillpredominate,whichcouldbeformedbytheapproachoftheenteringgroupfromtheleasthinderedsidewhentherotationalconformationoftheC-Cbondissuchthatthedoublebondisflankedbythetwoleastbulkygroupsattachedtotheadjacentasymmetriccenter.

Theruleindicatesthatthepresenceofanasymmetriccenterinamoleculeinducestheformationofanasymmetriccenteradjacenttoitbasedonsterichindrance.

Inhis1952publicationCrampresentedalargenumberofreactionsdescribedintheliteratureforwhichtheconformationofthereactionproductscouldbeexplainedbasedonthisruleandhealsodescribedanelaborateexperiment（scheme1）makinghiscase.

Theexperimentsinvolvedtworeactions.Inexperimentone2-phenylpropionaldehyde（1,racemicbut（R）-enantiomershown）wasreactedwiththeGrignardreagentofbromobenzeneto1,2-diphenyl-1-propanol

（2）asamixtureofdiastereomers,predominantlythethreoisomer（seeforexplanationtheFischerprojection）.

Thepreferencefortheformationofthethreoisomercanbeexplainedbytherulestatedabovebyhavingtheactivenucleophileinthisreactionattackingthecarbonylgroupfromtheleasthinderedside（seeNewmanprojectionA）whenthecarbonylispositionedinastaggeredformationwiththemethylgroupandthehydrogenatom,whicharethetwosmallestsubstituentscreatingaminimumofsterichindrance,inagaucheorientationandphenylasthemostbulkygroupintheanticonformation.

Thesecondreactionistheorganicreductionof1,2-diphenyl-1-propanone2withlithiumaluminiumhydride,whichresultsinthesamereactionproductasabovebutnowwithpreferencefortheerythroisomer（2a）.Nowahydrideanion（H−）isthenucleophileattackingfromtheleasthinderedside（imaginehydrogenenteringfromthepaperplane）.

Intheoriginal1952publication,additionalevidencewasobtainedforthestructuralassignmentofthereactionproductsbyapplyingthemtoaChugaevelimination,whereinthethreoisomerreactstothecisisomerof-α-methyl-stilbeneandtheerythroisomertothetransversion.

Felkinmodel[edit]

TheFelkinmodel（1968）namedafterHughFelkinalsopredictsthestereochemistryofnucleophilicadditionreactionstocarbonylgroups.[4]FelkinarguedthattheCrammodelsufferedamajordrawback:

aneclipsedconformationinthetransitionstatebetweenthecarbonylsubstituent（thehydrogenatominaldehydes）andthelargestα-carbonylsubstituent.Hedemonstratedthatbyincreasingthestericbulkofthecarbonylsubstituentfrommethyltoethyltoisopropyltoisobutyl,thestereoselectivityalsoincreased,whichisnotpredictedbyCram'

srule:

TheFelkinrulesare:

∙Thetransitionstatesarereactant-like.

∙Torsionalstrain（Pitzerstrain）involvingpartialbonds（intransitionstates）representsasubstantialfractionofthestrainbetweenfullyformedbonds,evenwhenthedegreeofbondingisquitelow.TheconformationintheTSisstaggeredandnoteclipsedwiththesubstituentRskewwithrespecttotwoadjacentgroupsoneofthemthesmallestinTSA.

ForcomparisonTSBistheCramtransitionstate.

∙ThemainstericinteractionsinvolvethosearoundRandthenucleophilebutnotthecarbonyloxygenatom.

∙Apolareffectorelectroniceffectstabilizesatransitionstatewithmaximumseparationbetweenthenucleophileandanelectron-withdrawinggroup.ForinstancehaloketonesdonotobeyCram'

srule,and,intheexampleabove,replacingtheelectron-withdrawingphenylgroupbyacyclohexylgroupreducesstereoselectivityconsiderably.

Felkin-Anhmodel[edit]

TheFelkin-Anhmodel[5]isanextensionoftheFelkinmodelthatincorporatesimprovementssuggestedbyNguyenT.AnhandO.EisensteintocorrectfortwokeyweaknessesinFelkin'

smodel.ThefirstweaknessaddressedwasthestatementbyFelkinofastrongpolareffectinnucleophilicadditiontransitionstates,whichleadstothecompleteinversionofstereochemistrybySN2reactions,withoutofferingjustificationsastowhythisphenomenonwasobserved.Anh'

ssolutionwastooffertheantiperiplanareffectasaconsequenceofasymmetricinductionbeingcontrolledbybothsubstituentandorbitaleffects.[6][7]Inthiseffect,thebestnucleophileacceptorσ*orbitalisalignedparalleltoboththeπandπ*orbitalsofthecarbonyl,whichprovidestabilizationoftheincominganion.

ThesecondweaknessintheFelkinModelwastheassumptionofsubstituentminimizationaroundthecarbonylR,whichcannotbeappliedtoaldehydes.

IncorporationofBü

rgi–Dunitzangle[8][9]ideasallowedAnhtopostulateanon-perpendicularattackbythenucleophileonthecarbonylcenter,anywherefrom95°

to105°

relativetotheoxygen-carbondoublebond,favoringapproachclosertothesmallersubstituentandtherebysolvetheproblemofpredictabilityforaldehydes.[6][10][11]

Anti–Felkinselectivity[edit]

ThoughtheCramandFelkin–Anhmodelsdifferintheconformersconsideredandotherassumptions,theybothattempttoexplainthesamebasicphenomenon:

thepreferentialadditionofanucleophiletothemoststericallyfavoredfaceofacarbonylmoiety.However,manyexamplesexistofreactionsthatdisplaystereoselectivityoppositeofwhatispredictedbythebasictenetsoftheCramandFelkin–Anhmodels.Althoughbothofthemodelsincludeattemptstoexplainthesereversals,theproductsobtainedarestillreferredtoas"

anti-Felkin"

products.Oneofthemostcommonexamplesofalteredasymmetricinductionselectivityrequiresanα-carbonsubstitutedwithacomponentwithLewisbasecharacter（i.e.O,N,S,Psubstituents）.Inthissituation,ifaLewisacidsuchasAl-iPr2orZn2+isintroduced,abidentatechelationeffectcanbeobserved.ThislocksthecarbonylandtheLewisbasesubstituentinaneclipsedconformation,andthenucleophilewillthenattackfromthesidewiththesmallestfreeα-carbonsubstituent.[12]IfthechelatingRgroupisidentifiedasthelargest,thiswillresultinan"

product.

ThisstereoselectivecontrolwasrecognizedanddiscussedinthefirstpaperestablishingtheCrammodel,causingCramtoassertthathismodelrequiresnon-chelatingconditions.[13]Anexampleofchelationcontrolofareactioncanbeseenhere,froma1987paperth