完整word版Felkin规则和Cram规则不对称诱导.docx

完整word版Felkin规则和Cram规则不对称诱导.docx

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完整word版Felkin规则和Cram规则不对称诱导

费尔金—安过渡态模型（Felkin—Anh模型）是一个用来解释α-手性酮亲核加成反应中产物的立体选择性现象的理论模型。

是对克莱姆模型（Cram规则）的发展.

历史

该模型由费尔金在1960年代提出。

1976年经安和埃森斯坦修正后得名,故有时也称费尔金-安-埃塞斯坦模型。

费尔金是法国化学家，安是一个姓阮（NguyễnTrọngÁnh/Anh，阮仲映/英/婴?

）的旅法越南化学家。

模型图示

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.

IncorporationofBürgi–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”anti—Felkin"product.

ThisstereoselectivecontrolwasrecognizedanddiscussedinthefirstpaperestablishingtheCrammodel,causingCramtoassertthathismodelrequiresnon-chelatingconditions.［13］Anexampleofchelationcontrolofareactioncanbeseenhere,froma1987paperthatwasthefi