pericyclic reactions 6 lectures, year 3, michaelmas...

Pericyclic Reactions 1

Pericyclic Reactions 6 Lectures, Year 3, Michaelmas 2016

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︎ ︎PericyclicReac+ons,OxfordChemistryPrimerno.67;IanFleming︎OrganicChemistryJonathanClayden,NickGreeves,StuartWarren,PeterWothersAdvancedOrganicChemistry:Reac+ons,MechanismsandStructures;JerryMarchFron+erOrbitalsandOrganicChemicalReac+ons;IanFlemingMolecularOrbitals&OrganicChemicalReac+ons;IanFlemingModernPhysicalOrganicChemistry;EricAnslynandDennisDocherty

π4s

π2s

HOMOdiene

LUMOdienophile

6electronsnonodesHückelallowed✓

O

O

O

O

O

O

(4q+2)s=1(4r)a=0Total=1odd✓allowed construcZveoverlap✓

h)p://burton.chem.ox.ac.uk/teaching.html


SynopsisThenatureofpericyclicreacZons

ExamplesofpericyclicreacZons

Drawingmolecularorbitals

CorrelaZondiagrams

TheWoodward-Hoffmannrule

FronZerMolecularOrbitals

Möbius-HückelMethod

CycloaddiZons

ElectrocyclicreacZons

Sigmatropicrearrangements

GrouptransferreacZons


Thenatureofpericyclicreac>onsIonicreacZons–mayormaynothaveanintermediate

SN1reacZonsarestepwiseandhaveadefinedintermediate

XMe

MeMe

NuMe

MeMe

MeMeMe

NuMe

EtH

IMe

EtH

Me

Et HINu

(") (")

‡

SN2reacZonsareconcertedandhavenointermediate

InionicreacZonsthecurlyarrowsidenZfywheretheelectronshavecomefromandwheretheyaregoingandwhichbondshavebeenmadeandwhichbroken.

RadicalreacZonsinvolvethecorrelatedmovementofsingleelectrons

frequentlyshortenedto

XMe

MeMe Me

MeMe Nu

NuMe

MeMe

IMe

EtHNu

Me

Et HINu

($) ($)Nu

Me

EtH + I

‡

+

NN

CN

NC

NN

CN

NC


PericyclicReac>onsThirddisZnctclassofreacZons

PericyclicreacZons–ReacZonsinwhichallfirst-orderchangesinbondingrelaZonshipstakeplaceinconcertonaclosedcurve.R.B.WoodwardandR.Hoffmann1969.i.e.thereacZonshavecyclictransiZonstatesinwhichallbond-formingandbond-breakingtakeplaceinaconcertedmannerwithouttheformaZonofanintermediate.

O

O

O

O

O

O

H H

PericyclicreacZonsinvolveatransiZonstatewithacyclicarrayofinteracZngorbitals;areorganisaZonofσandπ-bondsoccurswithinthiscyclicarray.

Originallytermed‘nomechanismreacZons’–theycouldnotbeexplainedbystandardnucleophile/electrophilemechanisms.

Noabsolutesenseinwhichtheelectronsflowfromonecomponenttoanother;however,someZmesitismoresensibletopushthearrowsinonlyonedirecZon.

Herecurlyarrowsareusedtoshowwhichbondsarebeingmade/brokenratherthanthedirecZonofflowofelectrons.


PericyclicReacZons–fourclasses.CycloaddiZons-Twocomponentscometogethertoformtwonewσ-bondsattheendsof

bothcomponentsandjoiningthemtogethertoformaring.

CheletropicreacZonsareasub-classofcycloaddiZonreacZonsinwhichthetwoσ–bondsaremadeorbrokentothesameatom.

ElectrocyclicReacZons–UnimolecularreacZonscharacterisedbytheforma>onofaringfromanopenchainconjugatedsystemwithaσ-bondformingacrosstheendsoftheconjugatedsystem.

O

O

O

O

O

O

NOMe

Me

NOMe

Me

O

CO+


OHMeO OMeOH

H

H H

OO

Sigmatropicrearrangements–Unimolecularisomerisa>onswhichformallyinvolvetheoverallmovementofaσ-bondfromoneposiZontoanother.

Coperearrangement Claisenrearrangement

[1,5]-hydrideshiK

[3,3] [3,3]

[1,5][3,4]

123

123

123

123

1

23

4

5 1

1 2

3

1 23

4

Grouptransfer–appeartobeamixofasigmatropicrearrangementandacycloaddiZon.Theyarebimolecularandsoarenotsigmatropicrearrangements,andnoringisformedsotheyarenotcycloaddiZons.

Alder-ene-reac>onsdiimidereduc>on

HO

O

O

HO

O

O

SeH

OPhSe

OPhH

HNN

HNN

H H


X

Me

Me

Me

Me

HMe

HMeH

Me

Me

MeMe

Requireatheory/theoriestoexplaintheseresults

O

O

O

O

O

O

O

O

O

O

O

O

X

heat

heat

MeH Me

HH

Me

HH

[1,5] [1,5]

heat

heat[1,7]

HMe

Me

H

[1,5]

HMe

HMe[1,7]

heat


HückelMolecularOrbitalTheoryforLinearπ-systems.Applicabletoconjugatedplanarcyclicandacyclicsystems.

Onlytheπ-systemisincluded;theσ-frameworkisignored(inrealityσ-frameworkaffectsπ-system).

UsedtocalculatethewavefuncZons(ψk)andhencerela+veenergiesbytheLCAOmethod.

MO=ψk,AO=ϕiandψ=Σckiϕii.e.ψk=c1ϕ1+c2ϕ2+c3ϕ3+c4ϕ4+c5ϕ5…..k=MOnumber(1→n);i=atomposiZoninπsystem(1→n);n=numberofp-orbitals

ForncontribuZngp-orbitalstherewillbenmolecularorbitals cki=(2/(n+1))1/2•sin(πki/(n+1))

ForeachMOψkΣci2=1(normalisaZon)i.e.thesumofthesquaresofthe

coefficientsforanyMOmustbe1.ForeachAOϕiΣck2=1i.e.thesumofthesquaresofthecoefficientsforanyAOoverallMOsmustbe1.

EachMOmustbesymmetricoranZsymmetricwithrespecttoanysymmetryoperaZonofthemolecule.

MolecularOrbitalEnergies=Ek=α+mjβ mj=2cos[jπ/(n+1)] j=1,2……n

n

i=1

ϕ1ϕ2ϕ3ϕ4

0.707 $0.707

0.500 0.500$0.707

0.500 0.5000.707


Todrawamolecularorbitaldiagram:i)  countthenumberofp-orbitals–nii)  countthenumberofelectrons–π-bond=2,unpairedelectron=1,carbanion=2,carbocaZon=0iii)  drawnhorizontallinesstackedontopofoneanothertorepresenttheMOsiv)  drawthemolecularorbitalsasthecombinaZonofp-orbitalswithanincreasingnumberofnodesfrom0for

ψ1ton-1forψnsuchthateachMOissymmetricoran0symmetricwithrespecttoanysymmetryopera0onofthemolecule.

v)  ifthenumberofnodesiseventhentheterminalorbitalcoefficientswillbethesamephasevi)  ifthenumberofnodesisoddthentheterminalcoefficientswillbeofoppositephase

ethene allyl butadiene pentadienyl hexatriene

• • •

•

•

non#bonding

ψ1

ψ2

ψ2

ψ1 ψ1ψ1

ψ1

ψ2ψ2

ψ2

ψ3

ψ3

ψ3

ψ3

ψ4

ψ4ψ4

ψ5

ψ6

ψ5

increasingnumberofnodes

0

1

2

3

4

5


six2patomicorbitalsgive6πmolecularorbitals;n=6,j=1,2,3,4,5,6

1,3,5-Hexatriene

MO no.nodes energy HMOTMO(calculated)

ψ6 5 α-1.80β

ψ5 4 α-1.25β

ψ4 3 α-0.45β

ψ3 2 α+0.45β

ψ2 1 α+1.25β

ψ1 0 α+1.80β

stabilisaZonenergy=Estab=2(3α+3.5β)=6α+7βrememberEstab(ethene)=2α+2β

α

mj=2cos(π/7)=1.80 2cos(2π/7)=1.25 2cos(3π/7)=0.45...... andthecorrespondingnegaZvevalues

energyE=α+1.80β α+1.25β α+0.45β α–0.45β…..etc

0.5210.232 '0.418

'0.418 0.2320.521

0.521&0.232 0.418

&0.418 0.232&0.521

0.232%0.418 %0.521

0.521 0.418%0.232

0.2320.418 0.521

0.521 0.4180.232

0.4180.521 (0.232

0.232 (0.521(0.418

0.418&0.521 0.232

0.232 &0.5210.418


TheHOMOof(neutral)polyenescanbereadilyconstructedbypuxngnodesonthesinglebonds;hencetheHOMOappearstobealternaZngisolatedπ-bondingpairs.TheLUMOof(neutral)polyenescanbeconstructedbybeginningwithan‘isolated’p-orbitalandthenalternaZng

‘isolated’π-bondingpairsandendingwithan‘isolated’p-orbital.

• • • • • •

HOMO

• • • • • •

LUMO

TheHOMOandLUMOaretermedtheFronZerOrbitals.

CorrelaZonDiagramsDuringapericyclicreacZontheorbitalsofthestarZngmaterialaresmoothlyconvertedintotheorbitalsofthe

product.ThismeansthatthesymmetryoftheorbitalswithrespecttoanysymmetryoperaZonsofthemoleculemustbe

conservedinmovingfromthestarZngmaterial(s)toproduct–thisisthe‘ConservaZonofOrbitalSymmetry’,whichisreadilydepictedinan‘orbitalcorrelaZondiagram’


DrawbarebonesofreacZon.

ψ1

ψ3

ψ2

ψ4

π

π*

σ1

σ2

π

σ3

σ4

π*

S

S

A

S

A

AA

S

A

S

A

S

σ σ

IdenZfyorbitalsundergoingchange.

Drawsensibleapproachofsubstrates.

IdenZfysymmetryelementsmaintainedduringreacZon.

Rankorbitalsapproximatelybyenergy.

Classifyeachorbitalwithrespecttothesymmetryelement(s)conservedduringreacZon.

ConstructorbitalcorrelaZondiagramconnecZngorbitalsofstarZngmaterialswiththoseclosestinenergyandofthesamesymmetryintheproduct.

IntheDiels-AlderreacZonaplaneofsymmetry,perpendiculartothemolecularplanesofboththedieneanddienophileandpassingthroughthedoublebondofthedienophileandthecentralsinglebondofthediene.

IntheorbitalcorrelaZondiagramoftheDiels-AlderreacZonallinteracZngbondingorbitalsinthediene/dienophilearecorrelatedwithnewbondingorbitalsintheproduct.ThereacZonisthermallyallowed.


CorrelaZondiagramfor[2+2]cycloaddiZonofalkenes

σ1

σ2

σ1

σ2

π2

π1

π3

π4

σ1

σ2

σ3

σ4

SS

SA

AS

AA

SA

AS

SS

AA

σ1σ2σ1σ2

IdenZfyorbitalsundergoingchange(curlyarrowstelluswhichorbitalstheseare)–π.

Drawsensibleapproachofsubstrates–inthiscasefaceonapproachofthetwoalkenesformaximumorbitaloverlap.

IdenZfysymmetryelementsmaintainedduringreacZon–inthiscasetwoplanesofsymmetry,σ1andσ2.

Rankorbitalsapproximatelybyenergy.

Classifyeachorbitalwithrespecttosymmetryelement(s)conservedduringreacZon.

ConstructorbitalcorrelaZondiagramconnecZngorbitalsofstarZngmaterialswiththoseclosestinenergyandofthesamesymmetryintheproduct.

Herethegroundstateπ12π2

2doesnotcorrelatewiththegroundsateoftheproduct(σ12σ22)butwithadoublyexcitedstateσ12σ32–thethermal[2+2]cycloaddiZonofalkenesisthermallydisallowed.

Formoreoncorrela+ondiagramssee:R.B.Woodward,R.Hoffmann,Angew.Chem.Int.Ed.1969,8,781-932.


CorrelaZondiagramforelectrocyclicreacZons

Z,E:E,E20,000:1

Longuet-Higgins&Abrahamson,J.Am.Chem.Soc.,1965,87,2045.

Therearetwomodesofopening–conrotatoryordisrotatory

Conrotatory–rota+onaroundtheaxesoftheσ-bonds(do]edlines)occursinthesamedirec+on-throughoutthisprocessthemoleculeretainsaC2-axiswhichpassesthroughtheplaneofthemoleculeandthebreakingσbond.

Disrotatory–rota+onaroundtheaxesoftheσ-bonds(do]edlines)occursinoppositedirec+ons–throughoutthisprocessthemoleculeretainsaplaneofsymmetrywhichisperpendiculartotheplaneofthemoleculeandpassesthroughthebreakingσ-bond

σplanview

C2planview

Me

Me

MeMe


RRRR R Rconrotatory disrotatory

R R

RR

RR

RR

CorrelaZondiagramforelectrocyclicreacZons.

σ

σ*

ψ1

ψ3

ψ2

ψ4

ψ1

ψ3

ψ2

ψ4

underσunderC2

π

π*

RR

RR

RR

RR

RR

RR

RR

RR

C2 σ

molecular)plane

IdenZfyorbitalsundergoingchange(curlyarrows)–σandπ.TheorbitalsundergoingchangeareeithersymmetricoranZsymmetricwithrespecttothe

symmetryelementspreservedduringthereacZon.Rankorbitalsapproximatelybyenergy.Labelorbitalsas‘S’or‘A’.ConstructorbitalcorrelaZondiagramconnecZngorbitalsofstarZngmaterials

withthoseclosestinenergyandofthesamesymmetryintheproduct.


Intheconrotatorymode,allgroundstatebondingorbitalsincyclobutene(σ2π2)correlatewithgroundstatebondingorbitalsinbutadiene(ψ1

2ψ22)–theconrotatoryopeningofbutadieneisthermallyallowed(favoured).

Inthedisrotatorymode,thegroundstatebondingorbitalsincyclobutene(σ2π2)correlatewithadoublyexcitedstateofbutadiene(ψ1

2ψ32)–thedisrotatoryopeningofbutadieneisthermallyforbidden(disfavoured).

Thephotochemicalringclosureofbutadienetogivecyclobuteneisdisrotatory.The1stexcitedsateofbutadieneisψ1

2ψ21ψ3

1whichcorrelatessmoothlywiththe1stexcitedsateofcyclobutene(σ2π1π*1);underconrotatoryringclosureψ1

2ψ21ψ3

1correlateswithamuchhighenergystateincyclobutene(σ1π2σ*1).

RRRR R Rconrotatory disrotatory

R R

RR

RR

RR

σ

σ*

ψ1

ψ3

ψ2

ψ4

ψ1

ψ3

ψ2

ψ4

underσunderC2

π

π*

AS

S

S

S

A

A A

SS

A

A

A

S

S

A

RR

RR

RR

RR

RR

RR

RR

RRC2 σ

molecular)plane

hν


CorrelaZondiagramscanbedisZlledintoasimpleruleforpredicZngwhichpericyclicreacZonsare“allowed”.TheWoodward-HoffmannRules:

Drawa‘curlyarrow’mechanismtoidenZfythecomponents.

FortheDiels-AlderreacZontheseare4π(diene)and2π(dienophile).

Drawaconvincing3-Dorbitaldiagramtoshowtheoverlapofthecomponents.

Labelthecomponentsassupraorantarafacial.

SumthecomponentsaccordingtotheWoodward-Hoffmannrule.

Apericyclicchangeinthefirstelectronicallyexcitedstate(i.e.aphotochemicalreacZon)issymmetry-allowedwhenthetotalnumberof(4q+2)sand(4r)acomponentsiseven.

AgroundstatepericyclicreacZonissymmetryallowedwhenthetotalnumberof(4q+2)sand(4r)acomponentsisodd(qandrmustbeintegers).

WewillusetheDiels-AlderreacZontoexemplifytheapplicaZonoftheWoodward-Hoffmannrules.


HH

(4q+2)s=(4r)a=Total=

Drawa‘curlyarrow’mechanism–thisgenerallyallowsidenZficaZonofthecomponents.

FortheDiels-AlderreacZontheseare4π(diene)and2π(dienophile),

Drawaconvincing3-Dorbitaldiagramtoshowtheoverlapofthecomponents.

Labelthecomponentsassupraorantarafacial.Herethedieneisbeingusedinasuprafacialmanner–thetwonewbondsarebeingformedonthesamefaceofthediene.ThealkeneisalsobeingusedinasuprafacialmannerbeingusedinasuprafacialmannerSumthecomponentsaccordingtotheWoodward-Hoffmannrule

π4s

π2s

π2a

π2s

π2aπ2s

π2s

π2s

π2s

π2s

π2a

Generallysimplesttomaximisesuprafacialcomponentsandnotsubdivideconjugatedsystems.

X

odd✓allowed

101

(4q+2)s=(4r)a=Total=odd✓allowed

303


101

(4q+2)s=(4r)a=Total=even✗

forbidden

202


O

O

O

O

O

O

[2+2]cycloaddiZons

Drawaconvincing3-DorbitaldiagramtoshowtheoverlapofthecomponentsLabelthecomponentsassupraorantarafacial.SumthecomponentsaccordingtotheWoodward-Hoffmannrule

π2s

π2s

π2s

π2a

Drawa‘curlyarrow’mechanismtoidenZfythecomponents–2π,2π

heat

π2s

π2a

butgeometricallyunreasonable,thereforedoesnotoccur

Woodward-Hoffmannrulegivesyouthesymmetryallowedorbitaloverlapbutyouhavetodecidewhethertheoverlapyouhavedrawnisgeometricallyreasonable.

X


forbidden(thermally)

202


(thermally)

101

(4q+2)s=(4r)a=Total=even✓

allowed–photochemically

202


Nomenclatureforsuprafacialandantarafacialcomponents.

SuprafacialandantarafacialrefertomodesofbondformaZonthatarerespecZvelyonthesamefaceoronoppositefacesofamolecularcomponent.

π-suprafacial π-antarafacial

σ-suprafacial

σ-antarafacial

σ-suprafacial σ-antarafacial ω-suprafacial ω-antarafacial

C H


MeMe

H H

MeMe

H H

MeMe

H H

Woodward-HoffmannapproachforthermalelectrocyclicreacZons

Drawa‘curlyarrow’mechanismtoidenZfythecomponents–theseare2π(alkene)and2σ(singlebond)

Drawaconvincing3-Dorbitaldiagramtoshowtheoverlapofthecomponents



σ2s

π2a

σ2a

π2s

π2s

σ2s

MeMeX

Thermalringopeningofcyclobuteneisconrotatory.Thermaldisrotatoryopeningissymmetryforbidden.

Me

Me

MeMe


(conrotatory)

101


(conrotatory)

101


forbiddendisrotatory

202


Me

O

Me

Woodward-Hoffmannapproachforsigmatropicrearrangements

Drawa‘curlyarrow’mechanismtoidenZfythecomponents–2π,2σ,2π




Woodward-HoffmannruledoesnottellusthatthechairTSislowerinenergythantheboatTS.Youneedtouseyourchemicalknowledge/intuiZontodecidethatachairisgenerallylowerinenergythanthecorrespondingboatandthatitisgenerallymorefavourabletohaveequatorialsubsZtuentsthanaxialsubsZtuentsonachair.

ClaisenrearrangementviachairTSisallowed. ClaisenrearrangementviaboatTSisallowed.

Me

Me

O

Me

Me

O

π2s

π2sπ2s

π2s

σ2sσ2s

π2s

π2sσ2s

OOMe

Me

Me

Me


303


303


O

SPh

Woodward-Hoffmannapproachforsigmatropicrearrangementsandgrouptransfer

Drawa‘curlyarrow’mechanismtoidenZfythecomponents




ene-reacZon(grouptransfer)viaenvelopeTS.

π2s

ω2s

σ2s

O

SPh

H H

π2s

π2sσ2s

[2,3]-sigmatropicrearrangementviaenvelopeTS.

SO Ph

OSPh

HO

O

O

HO

O

O

ForthermalcycloaddiZonsandgrouptransfers:Ifthetotalnumberofelectronsis(4n+2)bothcomponentscanbeusedinasuprafacialmanner. Ifthetotalnumberofelectronsis(4n)oneofthecomponentsissuprafacialandtheotherantarafacial.

ForelectrocyclicreacZons:Thermalelectrocyclicprocesseswillbeconrotatoryifthetotalnumberofelectronsis4nanddisrotatoryifthe

totalnumberofelectronsis(4n+2).


303


303


hν

FronZerMolecularOrbitalapproach–revision‘Astwomoleculesapproacheachother,threemajorforcesoperate:(i)  Theoccupiedorbitalsofonerepeltheoccupiedorbitalsoftheother.(ii)  AnyposiZvechargeononea�ractsanynegaZvechargeontheother(andrepelsanyposiZve)(iii)  Theoccupiedorbitals(especiallytheHOMOs)ofeachinteractwiththeunoccupiedorbitals(especiallythe

LUMOs)oftheother,causingana�racZonbetweenthemolecules.’(fromFleming,MolecularOrbitalsandOrganicChemical

ReacZons)FronZerMolecularOrbitalconsiderstheinteracZonoftheHighestOccupiedMolecularOrbital(HOMO)andtheLowestUnoccupiedMolecularOrbital(LUMO)tobeofoverridingimportance.

HOMOb

LUMOa emptyMOa

filledMOb

emptyMOb

filledMOa

thermalreacZon

ForphotochemicalreacZonsonemoleculeisintheexcitedstate

aψ1

2ψ22

a*ψ1

2ψ21ψ3

1

ψ1

ψ3

ψ2

ψ4HSOMO

LSOMO

excitedstatea groundstateb

LSOMOa

unoccupiedMOψ3HSOMOa

occupiedMOψ2

•

••••

•• ••••

•

• •

••

b

LUMO

HOMOψ1

ψ3

ψ2

ψ4


TheFMOapproach

AssignasingleHOMOandasingleLUMOtothereacZon


ChecktoseeifthereisconstrucZveoverlapbetweentheorbitals


HOMOdiene

LUMOdienophile HOMOdienophile

LUMOdiene

(4q+2)s=1(4r)a=0Total=1odd✓allowed

π4s

π2s

construcZveoverlap✓ construcZveoverlap✓

ToapplytheFMOmethodonehastoassignasingleHOMOandasingleLUMOtothereacZoncomponentsandseehowtheyinteract.TheFMOapproachissimpletoapplytoreacZonswithtwocomponents(e.g.cycloaddiZons,electrocyclicring

opening)butitsapplicaZontosigmatropicrearrangementsandgrouptransferreacZonsissomewhatcontrived.


HMe

H Me

TheFMOapproach





Me

MeHMe

H Me

MeMe


(conrotatory) σ2a

π2s

Thepreferenceofoneconrotatory(ordisrotatory)modeistermedtorqueoselec+vity(morelater).

HOMOalkene

LUMOalkene LUMOalkene

HOMOsigma

HMe

H MeLUMOsigma

HOMOsigma construcZveoverlap

construcZveoverlap✓

Me

Me

MeMeheat

HMe

H Me



TheFMOapproach

AssignasingleHSOMOandasingleLUMOtothereacZon,(orasingleLSOMOandHOMO)–noteaHSOMOhasthesamephasesasthe‘LUMO’andaLSOMOhasthesamephasesastheHOMO)Drawaconvincing3-Dorbitaldiagramtoshowtheoverlapofthecomponents



(4q+2)s=0(4r)a=0Total=0even✓allowed

photochemically(disrotatory)

π4s

HOMOalkene

LSOMOalkene

construcZveoverlap✓(disrotatory)

MeMe

H H

Me Mehν

Me Me

hν


TheFMOapproach






Me

Me

O

π2s

π2sσ2s

ψ2

Me

Me

O

HOMObutadiene

HOMO‘π+σ’

LUMOalkene

ψ3

LUMObutadiene

Me

Me

O

LUMO‘π+σ’

HOMOalkene


OOMe

Me

Me

Me

Me

Me

O


O

Ph S

O

SPh

O

SPh (4q+2)s=3(4r)a=0Total=3odd✓allowed

π2s

ω2s

σ2s

O

SPh

TheFMOapproach





HOMOalkene

LUMO,σ+ωHOMOω

LUMO,alkene+σ

ψ3

LUMObutadiene

ψ3

LUMO4e-allyl


SO Ph

OSPh


TheMöbius-HückelMethod

AthermalpericyclicreacZoninvolvingaHückeltopologyisallowedwhenthetotalnumberofelectronsis(4n+2).AthermalpericyclicreacZoninvolvingaMöbiustopologyisallowedwhenthetotalnumberofelectronsis4n.(ForphotochemicalreacZonstherulesarereversed.)

Drawacurlyarrowmechanismtoassigncomponents

Drawaconvincing3-Dorbitaldiagramtoshowtheoverlapofthecomponents(easiesttodrawψ1forallcomponentsandminimisenumberofnodes).

CountthenumberofphaseinversionsintheclosedloopofinteracZngorbitals–asalways,phaseinversionswithinan(atomic)orbitalarenotcounted.

Evennumberofphaseinversions:Hückeltopology

Oddnumberofphaseinversions:Möbiustopology

nophaseinversions,Hückelsystem6electronsallowed✓

Diels-AlderreacZon

nophaseinversions,Hückelsystem4electronsforbidden(thermally)✗

[2+2]cycloaddiZon

nophaseinversionHückelsystem6electronsallowed✓

Sigmatropicrearrangement

Research: Science and Education

1536 Journal of Chemical Education • Vol. 84 No. 9 September 2007 • www.JCE.DivCHED.org

Hückel and Möbius Aromatics

Thus these two great concepts of organic chemistry, aro-maticity and chirality, remained mostly exclusive. EdgarHeilbronner in 1964 (4) and Howard Zimmerman in 1966(5) both came up with radical new suggestions that allow afusion of these concepts. Rather than distributing electronsin a planar ring comprising precisely parallel overlap of 2patomic orbitals, Heilbronner considered what might happenif this array were instead distributed along a Möbius stripbearing a single half (left or right) twist (Figure 3).

Heilbronner applied Hückel’s equations (3) to such a cy-clic Möbius ring, finding that a 4n -electron system wouldbe a closed-shell species like benzene, with no loss of -elec-tron resonance energy compared to the equivalent untwistedHückel ring. A closed-shell 4n 2 electron Möbius ringwas predicted to be less stable than the untwisted Hückelcounterpart.

Like Hückel before him, Heilbronner did not derive asuccinct rule of aromatic stability from these results.Zimmerman (5) was the first to clearly associate the -elec-tron stability of such Möbius rings with an inversion of thearomaticity rules 1 and 2 above. Specifically, populations of4n electrons result in closed-shell (two electrons per en-ergy level) molecules if the 2p atomic orbitals are distributedalong a Möbius strip (rule 1 inverted), whereas 4n 2 -electrons will adopt an open-shell (photochemical) distribu-tion in which two of the electrons will now each occupy aseparate molecular orbital (rule 2 inverted) (5). By adding acorollary for the anti-aromatic cases, rules 5–8 to comple-ment 1–4 can be listed:

5. 4n electrons, thermally (closed shell) aromatic andstable with Möbius topology

6. 4n 2 electrons, photochemically (open shell) aro-matic and stable with Möbius topology

7. 4n 2 electrons, thermally (closed shell) less stablewith Möbius topology

8. 4n electrons, photochemically (open shell) less stablewith Möbius topology.

A useful visual mnemonic first proposed by Frost andMusulin (6) for orbital energies of -electron rings based oninscribing a polygon with one vertex down for the Hückelrules, was memorably extended by Zimmerman (5) to Möbiussystems by redrawing the polygons with one edge down (Fig-ure 4).

Another aspect of Möbius systems that was not directlycommented upon by Heilbronner is that a Möbius strip bear-ing one half-twist is also chiral, in the sense noted above forthe heptahelicene molecule (Figure 2). An ideal Möbius striphas only a C2 axis of symmetry present. The specific absenceof a plane of symmetry means the mirror image of a Möbiusstrip is not superimposable upon the original. In contrast,an ideal planar aromatic molecule of the Hückel type doeshave at least one plane of symmetry, referred to here as a Csmirror plane, which means that its mirror image is superim-posable with the original. Thus in Möbius ringed molecules,we do now have a fusion of two seminal concepts in organicchemistry, that of aromaticity and of chirality!

Figure 2. A heptahelicene and its non-superimposable mirror image.

Figure 3. Heilbronner’s suggestion for a Möbius conjugated sys-tem obtained by electrons located in molecular orbitals resultingfrom 2p atomic orbitals distributed around a Möbius strip bearinga single half-twist, rather than a planar Hückel ring bearing notwist in the orbital basis.

Figure 4. Frost–Musulin and Zimmerman mnemonics for aromatic-ity selection rules. A six-sided polygon is shown for the Hückel caseto coincide with the example shown later in Scheme III (solid ar-rows) and an eight-sided polygon is shown for the Möbius case tocoincide with the dashed arrows in Scheme III.

fromH.S.RzepaJ.Chem.Ed.,2007,84,1535

O

Ph S


TheMöbius-HückelMethod

AthermalpericyclicreacZoninvolvingaHückeltopologyisallowedwhenthetotalnumberofelectronsis(4n+2).AthermalpericyclicreacZoninvolvingaMöbiustopologyis

allowedwhenthetotalnumberofelectronsis4n.(ForphotochemicalreacZonstherulesarereversed.)

nophaseinversions,Hückelsystem4electronsforbidden(thermally)✗(disrotatory)

onephaseinversionMöbussystem4electronsallowed✓(conrotatory)

electrocyclicreacZons

HMe

H Me

HMe

H Me

HMe

H Me

H

Me

H

Me

Me

Me

MeMe


OMe

O

CO2Me

H

H

O

MeO MeO

H

O

H

OOMe O

H

OMe

H

O O

H

CycloaddiZons

TheDiels-AlderreacZonisgreatlyacceleratedbyhavinganEDGonthedieneandanEWGonthedienophile.

165°C,17h900atm 150°C,0.5h

100°C,2h 120°C,6h

endo

AlCl3,-78°C‘ortho’and‘para’productspredominate.

‘endo’productspredominate.

LewisacidscatalysethereacZon.

Me

OMe

OMe

OMe

O Me

OMe

O

+

withoutcatalysis 90% 10%withAlCl3 98% 2%


•

ψ1

ψ2

ψ2

ψ1 ψ1

ψ2

ψ3

ψ3

ψ4

CycloaddiZons

IncreaserateofreacZonwithEWGondienophile.

α

0.230.43

0.660.58

0.580.58 )0.58

0

066)0.23 )0.43

)0.58

)0.430.66 0.23

)0.58

ψ1

ψ2

ψ3

ψ4O

H

HOMO

LUMO

α+1.00β

α-0.35β

α-1.53β

α+1.88β

α

O

O

HOMO

LUMO

HOMO

LUMO

AnEWG(‘Z’subsZtuent)onthedienophilelowerstheenergyoftheLUMO(andofallorbitals).(HOMOetheneisα+β,LUMOisα–β).ThebestenergymatchisthereforetheHOMOofthedienewith

theLUMOofthedienophile(fulldouble-headedarrow)ratherthantheHOMOofthedienophilewithwiththeLUMOofthediene(dasheddouble-headedarrow).CatalysisbyLewisacidsarisesfromfurtherloweringoftheLUMO

ofthedienophile.

O

AlCl₃

OAlCl₃

OAlCl₃


ψ1

ψ2

ψ1ψ1

ψ2ψ2

ψ3

ψ3

ψ4

ψ4

ψ5

CycloaddiZons

αα+0.62β

α-0.62β

α–1.62β

α+1.62β

α

HOMO

LUMO

0.37 0.370.600.60

0.60 &0.60&0.370.37

0.60 0.60&0.37&0.37

0.37 &0.370.60&0.60

ψ1

ψ2

ψ3

ψ4InasimilarmannerplacinganEDGonthedieneraisestheenergyoftheHOMOmakingitabe�erenergymatchfortheLUMOofthedienophile.

OMe

HavinganEDGonthedienophile(higherenergyHOMO)andanEWGonthediene(lowerenergyLUMO)isgenerallylesseffecZveatincreasingthelateoftheDiels-AlderreacZon.(Inverseelectrondemand)

Ingeneral:EWG(Z-subsZtuents)lowerHOMO&LUMOenergiesEDG(X-subsZtuents)raiseHOMO&LUMOenergiescarbonconjugaZngsystemse.g.C=C,raiseHOMO&lowerLUMO

Thesegroupsdistortorbitalcoefficients.


0.500

$0.707

0.500

0.5000.707

0.500

0.707 $0.707

0.37 0.370.600.60

0.60 $0.60$0.370.37

0.60 0.60$0.37$0.37

0.37 $0.370.60$0.60

O

O

O

O

0.55 $0.070.54

0.65 $0.54$0.19

0.44 0.55$0.65

0.19 0.300.30

CycloaddiZonsDiels-AlderreacZonregioselecZvity

0.707 $0.707

0.500 0.500$0.707

0.500 0.5000.707

O

0.230.43

0.660.58

0.580.58 )0.58

0

066)0.23 )0.43

)0.58

)0.430.66 0.23

)0.58

ψ1

ψ2

ψ3

ψ4

αHOMO

LUMO

α+1.00β

α-0.35β

α-1.53β

α+1.88β

HOMO

LUMO

0.370.600.60

&0.60&0.370.37

0.60&0.37&0.37

&0.370.60&0.60

ψ1

ψ2

ψ3

ψ4

largesmall

CoefficientsforacroleinjusttakenasaverageofallylcaZonandbutadienecoefficients–seeFleming.

InthepresenceofaLewisacid(e.g.AlCl3)acroleinwillhavemoreallylcaZoncharacterandhencetheC-terminuscoefficientoftheLUMOwillbelarger.

O

H

AlCl₃

OAlCl₃

OAlCl₃


0.37 0.370.600.60

0.60 &0.60&0.370.37

0.60 0.60&0.37&0.37

0.37 &0.370.60&0.60

0.50 &0.500.50 &0.50

0.29 0.500.580.50 0.29

0.580.58 &0.58

0.50 0.50&0.50 &0.50

0.29 &0.500.58&0.50 0.29

0.45 &0.260.55

0.15 0.250.290.25

0.59 &0.48

0.55 0.55&0.44

0.33 &0.440.59&0.55

0.30

0.19

&0.19

&0.30

CycloaddiZons

Diels-AlderreacZonregioselecZvity

HOMO

LUMO

OMe

large

0.37 0.370.600.60

0.60 &0.60&0.370.37

0.60 0.60&0.37&0.37

0.37 &0.370.60&0.60

0.50 $0.500.50 $0.50

0.29 0.500.580.50 0.29

0.580.58 $0.58

0.50 0.50$0.50 $0.50

0.29 $0.500.58$0.50 0.29

ψ1

ψ2

ψ3

ψ4

ψ5


CycloaddiZonsDiels-AlderreacZonregioselecZvity(Z=EWGe.g.CO2Me;X=EDGe.g.OMe.

HOMO

LUMO

Z

Z

X

X

C

C

Z

Z

X

X

C

C

HOMO

LUMO

HOMO

LUMO

HOMOdiene/LUMOdienophileisthepredominantinteracZon

Z X C

Z X CLarge-largeandsmall-smalloverlapisbest.

Asnotedpreviously,inthepresenceofaLewisacid(e.g.AlCl3)C-terminuscoefficientoftheLUMOofaZ-subsZtutedalkenewillbelargerleadingtoincreasedregioseleciZvityintheDiels-AlderreacZon.


Z

X

CycloaddiZonsDiels-AlderreacZonregioselecZvity(Z=EWGe.g.CO2Me;X=EDGe.g.OMe.

HOMO LUMO

HOMO LUMO

H

OOMe O

H

OMe

X

Z

‘ortho’product

‘para’product

H

OOMe

CNCN

CNCN

HOMO LUMO

Z

Z

H

O

MeO MeO

H

O

H

O

MeO

‘ortho’product


OMeO H

CycloaddiZonsDiels-AlderreacZontheendorule–endo-productisgenerallythemajorproductwithdienophilescontainingπ-

conjugaZngsubsZtuents.

OMe

O

CO2Me

H

H

CO2Menot

HOMO

LUMO

SecondaryorbitaloverlapisasimpleexplanaZonforthekineZcpreferencefortheendo-adduct–

HO

OMe

endo exoIncaseswherethereacZonreadilyreverses(e.g.DielsAlderreacZonswithfuran)thethermodynamically

preferredexo-adductsareusuallyobtained.

endo-kineZc exo-thermodynamic

O O

O

O

O

O

O

O

O

O

O

O


HOH

(+)

(+)

H

HHH

CycloaddiZonsElectrostaZcargumentshavealsobeenproposedasareasonableexplanaZonfor‘endo’-selecZvity

OMeO H

H

H

(+)

(+)

(+) HO

OMe

H

H

(+)

(+)

(+)

endo(favoured) exo(disfavoured)

Ph O

H

PhCHO

endo(disfavoured)

exo(disfavoured)

Stericeffectscanfavourtheexoproduct.

O

HMe

Me

O

H

exo

OH Me

H

H

MeO

H

H

H

OMe

O

CO2Me

H

OH H

(+)

(+)

Ph

H HH

endo

endo

exo(favoured)

endo(favoured)


OMeO

H

H

Me

OAc

HH

H

OMeO

H

H

Me

OAc

HH

H

O

MeH

HH

OAcCHO

CycloaddiZons–DrawingstereochemistryfortheDiels-Alder

O

Me

HH

H

OAc

H

H

H

O

Me

HH

H

OAc

H

H

H

O

Me

HH

H

OAc

H

H

H

12

3

4

56

12

3

4

56

OAcCHO

Me

endo

O

OAc

H

H

H

MeH

HH

OAc O

Me

HBF3•OEt2,*50*°C

?

Me

HH

H

OAc

H

H

H


TreaZngtheketeneasavinylcaZonallowsageometricallymorereasonableoverlaptoorthogonalorbitals

O

CycloaddiZonsKetenesundergo(thermal)[2+2]-cycloaddiZonswithalkenesprovidinganexcellentmethodforcyclobutanesynthesis.

• OCl

ClOCl

Cl

HH

H

H

• OCl

ClOCl

Cl

HH

ThesimplestexplanaZonforthisreacZonisthattheorbitalsoftheketeneareusedasanantarafacialcomponent.

O(4q+2)s=

(4r)a=Total=odd✓allowed

101

π2s

π2aπ2s

π2a

Cl Cl

•

O

Cl Cl

•

OO

R

R

ClCl

R R

O

π2s

π2a


101

ω0s


OO

O

OC

C

OC

C

CycloaddiZonsKeteneFronZerOrbitals

HOMO(C=Cπ)

LUMO(C=Oπ*)

LUMO+1(C=Cπ*)

HOMOalkene

LUMO+1ketene


HOMOalkene LUMOalkene

LUMOketene HOMOketeneWithketenesitisprobablethatthelowlyingC=Oπ*orbitalisinvolvedinthereacZon.

• OH

H OHH

Othercumulatedπsystemswhichcontainacentralsp-hybridisedcarbonatom(e.g.allenes,vinylcaZons)alsoreadilyundergo[2+2]cycloaddiZon.

OC

C


•

Cl

H

O O •Cl

H

•Cl

H

O

Withanunsymmetricalketene,thelargerketenesubsZtuentwillpointawayfromtheplaneofthealkene.

CycloaddiZons

HOMOdiene

LUMO+1ketene


InreacZonsofunsymmetricalalkenesthelessstericallydemandingC=OpartoftheketenewillbeorientedabovethelargeralkenesubsZtuents.

Ketenesreadilyreactwithcyclopentadienetogivecyclobutanes.


101

RegioselecZvitycanbepredictedfromsimple“arrow-pushing”arguments(theC=Ocarbonofketenesisveryelectrophilic),orfromlookingatFMOcoefficients.

•O

Cl H

H

H

O

Cl

Cl

H

O

π2s

π2a


•H

Cl

O

•O

Cl H

H

H

O

Cl

O

HCl

O

H

Cl

O

HCl

Certainketenesappeartoreactwithcyclopentadieneviabotha[2+2]cycloaddiZon,anda[4+2]cycloaddiZonfollowedbyaClaisenrearrangementmechanism.

CycloaddiZonsAnotherpossiblemechanismisaheteroDiels-AlderreacZonfollowedbyaClaisenrearrangement.

construcZveoverlap✓(4q+2)s=


101

π2s

π4s

HOMOdiene

LUMOketene

σ2sπ2s

π2s

•

HCl

O

HCl

O


Oxyallyl-diene

construcZveoverlap✓disrotatory


disrotatory

101

HOMOsigma

LUMOω

σ2s

ω0s O

O OO

O

OO O

O

HOMOdiene

LUMOallylcaZon


O


101

π2s

π4s


Ph

Ph

Ph

Br

AgBF4

Ph

Ph

Ph

Allylanion-alkeneandreverseprocess

AllylcaZon-diene

HOMOallylanion

LUMOalkene



101

π2s

π4sπ2s

Ph

H

LDA,%45%°C

PhPh

PhPh

Ph

Ph

HPh

Ph

Ph

π4s


Ph

OO

O

O

O

O Ph

H O

OPh

BuLi+ PhCO2

Allylanion-alkene(reverseprocess)

HOMOω

LUMOσ+σ

construcZveoverlap✓(4q+2)s=


303

σ2s

σ2s ω2s

ψ3

LUMObutadiene

O

O

HOMOcarboxylate

LUMOalkene


ItcanbeeasiertoanalysethereversereacZon.

PhO

O

O

OPh


1,3-DipolarcycloaddiZons.

sp-hybridizedcentralatom

ZY

Xπ4sπ2s X Y Z X Y Z X Y Z

1,3-dipole

nitrileylids

NRN

Cl

R

H B

nitrileoxides

N ORN

Cl

R

O H B

nitrileimines

N NHR

diazoalkanes

N NR

R

H2NN

R

RArSO2N3 +

R R

alkylazides

N N NR

X RN N N

nitrousoxide

N N O

oxidaZon


1,3-DipolarcycloaddiZons.

sp2-hybridizedcentralatom

π4sπ2s

1,3-dipole

azomethineylids azomethineimines

carbonyloxides carbonylylids

ozone

XY

Z XY Z X

YZ

ZY

X

NR

NNH

R

OO

O

nitrones

NO

R

OO

O


Ozonolysis

OO

O

OO

O

π4s

π2s(4q+2)s=


101

OO

O

HOMOalkene

LUMOozone

ψ3

LUMOallylanion


OO

O

OO

O

HOMOcarbonylLUMOcarbonyl


OO

C

O

HOMOcarbonylylid


LUMOcarbonylylid

•ψ2

HOMOallylanion

OO

O

OO

O

ω2sσ2sσ2s


Azomethineylids.

σ2s

ω2a


conrotatory

101

HOMOω

LUMOσ

construcZveoverlap✓conrotatory

Ph

CO2EtEtO2C

H H

ψ2

ψ1

ψ3

•

Ph

CO2EtEtO2C

H H

N

EtO2C CO2Et

H H

Ph

CO2Et

N CO2EtPh

Ph Ph

CO2Et

N CO2EtPh

NEtO2C CO2Et

Ph Ph

Ph

[π2sπ4s]


NH2OHN

NC

OCN

NNC

OCN

NNC

OHCN

NitronecycloaddiZons.NitronesarereadilyformedbetweenaldehydesandsubsZtutedhydroxylamines.

RNHOH

O

R' H

N

R' H

O R+ N

HR'

RO

ONR

R'

ThenitronecycloaddiZoncanpredominantlyHOMOnitroneLUMOdipolarophile,orLUMOnitroneHOMOdipolarophiledependingonthesubsZtuentsonthedipolarophile.

Stockmansynthesisofhistrionicotoxin;J.Am.Chem.Soc.,2006,128,12656.

N

HOH

NO

NOH

O

CNCN

N CNNC

ON CN

NC

O

N

O

heat180°C


N

CNMe

OMe

O

NOMe

CNMe

O

Gin’sNomininesynthesis–J.Am.Chem.Soc.,2006,128,8734.

N

H

H

Me

H

HOH

H

HN

X

H

HH

MeCN

MeN

OOMe

CN

MeN

OOMe

CN

N

H

H

Me

H

O

OMe

N

CNMe

OMe

OCN

N

H

H

Me

H O

OMe

NOMe

CNMe

O 1

3.6


N

H

H

Me

H

N

H

H

Gin’sNomininesynthesis–J.Am.Chem.Soc.,2006,128,8734.

i)#NaBH4ii)#SOCl2

i)#Bu3SnH,#AIBN

i)#DIBALii)#Ph3P=CH2

CN

N

H

H

Me

H

O

OMeCN

N

H

H

Me

H

Cl

OMeCN

N

H

H

Me

H

OMe

N

H

H

Me

H

OMe

H

N

H

H

Me

H

OMe

H

N

H

H

Me

H

O

H

N

H

H

Me

H

H

O

H

Na,$NH3,$iPrOHH+,$H2O

NH

,"MeOH

189

N

H

H

Me

H

H

N

H


O

CheletropicReacZons

Asub-classofcycloaddiZon/cycloreversionreacZonsinwhichthetwoσ–bondsaremadeorbrokentothesameatom.

O

CO+

MoreimportantarethereacZonsofsingletcarbeneswithalkeneswhicharestereospecific.

Cl

Cl

MeMe

MeMe

Cl Cl

Cl Cl

π2s

ω0a

ω2s(4q+2)s=


213

Cl

Cl

LUMOalkene

HOMOcarbene


Cl

ClLUMOcarbene

HOMOalkene


SideonapproachofthecarbeneisrequiredforconservaZonoforbitalsymmetry.

π2s

π2a

ω0s


101

c.f.ketenesasvinylcaZons

Cl Cl

•

O

Cl Cl

•

OO

R

R

ClCl

R R


O

S O

CheletropicReacZons

TheotherimportantcheletropicreacZonsinvolvethereversibleaddiZonofsulfurdioxidetopolyenes.

ω2s (4q+2)s=(4r)a=Total=odd✓allowed

101

LUMOdiene

HOMOSO2


LUMOSO2

HOMOdiene


SO2SO2

SO2SO2

π4sO

S O

O

S OHOMO–lonepair

LUMO

O

S O

O

S O

heatandpressure

heatandpressure


SO2

heatSO2

heat

%&SO2%&SO2

OS

O

OS

O

CheletropicReacZons

WithtrienestheextrusionprocessdominatesbutconsideringthereverseprocessthereacZonmustbeantarafacialwithrespecttothetrienecomponent.

ω2s


101

LUMOtriene

HOMOSO2


LUMOSO2

HOMOtriene


π6a

HOMO–lonepair

LUMO

OS

O

SO O

X toostrained;ca.104ZmeslessreacZvethan SO2

LUMOhexatriene


CheletropicReacZonsinSynthesis

SO2

OOMeMe O

H

Me O

H

Me O

H H

H

OOMe

MeO

Me

HHO

Me

SO2Me

H

OOMe

MeO

Me

HHO

Me

Me

O

OMe

Me

O

Me

HHO

Me

Me

H

H

HO

OMe

MeO

Me

HO

MeHMe

H

exo

endo

Steroidsynthesis

Colombiasin


MeMe

Me

Me

Me

Me

Me

Me


Thermalelectrocyclicprocesseswillbeconrotatoryifthetotalnumberofelectronsis4nanddisrotatoryifthetotalnumberofelectronsis(4n+2)–thisisreversedforphotochemicalreacZons.

AllelectrocyclicreacZonsareallowed(providedtheyarearenotconstrainedbythegeometryoftheproduct).


disrotatory

101

MeMe

π6s

HMeMe


disrotatory

101

π6s

140°C,5h 140°C,5h

Me MeH HH

Me

H

Me


conrotatory

101X

butgeometricallyconstrainedthereforedoesnotoccur.

H H

MeMe

π2a

σ2s


Me

Me MeMe

Ph

Ph

Ph

Ph

ElectrocyclicreacZons(4q+2)s=

(4r)a=Total=even✓allowed

conrotatory

000

π4shν PhPh

Me Meσ2a

PhPh

Me Me

HSOMOdiene

LUMOσ


CyclopropylcaZon/allylcaZoninterconversion

TheionisaZonofcyclopropylhalidesandtosylatesisaconcertedprocesstogiveallylcaZons(i.e.discretecyclopropylcaZonsarenotformed).

ThereacZoncanbeviewedasaninternalsubsZtuZoninwhichtheelectronsinaσ-bond(HOMO)feedintotheC-Xσ*(LUMO).

ThereacZonisdisrotatoryandthesenseofrotaZon(torquoselecZvity)isspecified–thisdictatesthegeometryoftheallylcaZonandcanhavealargeinfluenceonreacZonrate.

Cl Cl Cl

Lewisacidlowtemperature

ψ2

ψ1

ψ3

•


Cl

H

H

Me

Me

Cl

Me

Me

H

H



odd✓allowed

disrotatory

101

ω0sHOMOσ

LUMOσconstrucZveoverlap✓disrotatory

Cl

Me

H

H

Me


Cl

H

H

Me

Me

Cl Cl Cl


σ2s

X

Influenceonrates–solvolysisinaceZcacid

OTs

HH

HH

OTs

HH

MeH

OTs

MeH

HH

OTs

HH

MeMe

OTs

MeH

HMe

OTs

MeMe

HH

1 6 133 2 450 37000


OMe3SiFeCl3

OMe3SiFeCl3 Me3Si

OFeCl3

H H H H

H

O

H H

H

ElectrocyclicreacZons-pentadienylsystems.

CaZonic-NazarovreacZon.

6πelectrocyclicringclosure

relaZveconfiguraZonsetbypericyclicreacZon

H H

O (4q+2)s=(4r)a=Total=odd✓allowed

conrotatory

011

π4a

H H

O

HOMOallylcaZon

LUMOalkene


ThermalNazarovcyclisaZonisconrotatory;photochemicalNazarovreacZonisdisrotatory.

Anionic.

N N

Ph

Ph Ph

H PhLiN N

Ph

Ph Ph

NN

Ph Ph

Ph

Ph PhH H

Phπ6s (4q+2)s=(4r)a=Total=odd✓allowed

disrotatory

101

4πelectrocyclicringclosure


HH

HHCO2Me

Ph

HH

H

PhCO2Me

HH

H

CO2MePh

ElectrocyclicreacZonsexemplified–theendiandricacids.

HH

H

CO2Me

H

H

Ph

HendiandricacidAmethylester

endiandricacidDmethylester

endiandricacidEmethylester

endiandricacidFmethylester

H

H

HCO2MeH

PhH

H

endiandricacidCmethylester

endiandricacidGmethylester

HH

HH CO2MePh

HH

H

H

H

Ph

H

CO2Me

endiandricacidBmethylester

CO2MePh

HH

CO2MePh

HH

Ph

HH

CO2MePh CO2Me

CO2Me

Ph

DielsAlder DielsAlder DielsAlder

8πelectrocyclic

6πelectrocyclic

6πelectrocyclic

6πelectrocyclic

8πelectrocyclic

BiosynthesisproposedbyBlackJ.Chem.Soc.,Chem.Commun.,1980,902.

BiomimeZcsynthesisbyK.C.Nicolaou,J.Am.Chem.Soc.,1982,104,5558.


HH

CO2Me

Ph

HH

H

CO2MePh

CO2Me

Ph

R

R'

HH

ElectrocyclicreacZonsexemplified–theendiandricacids.

CO2Me

Ph

CO2Me

Ph

HH

π8a

CO2MePh

HH

8πelectrocyclicringclosure-conrotatory

6πelectrocyclicringclosure-disrotatory

HH

H

CO2Me

H

H

Ph

H

π6s

R

R'

HH

π6s6πelectrocyclicringclosure-disrotatory

exo-DielsAlderreacZon

endiandricacidAmethylester

endiandricacidDmethylester

endiandricacidEmethylester

H2Lindlar

heat,100°C

HH

HHCO2Me

Ph

HH

CO2Me

Ph


HHPh

CO₂Me

HHPh

CO₂Me

HH

H

PhCO2Me

H

H

HCO2MeH

PhH

H

HH

H

H

H

Ph

H

CO2Me

Ph

HH

CO2Me

Ph CO2Me

Ph CO2MePh

CO2Me

R

R'

HH

ElectrocyclicreacZonsexemplified–theendiandricacids.π8a

8πelectrocyclicringclosure-conrotatory

6πelectrocyclicringclosure-disrotatory

π6s

R

R'

HH

π6s6πelectrocyclicringclosure-disrotatory

exo-DielsAlderreacZon

endiandricacidBmethylester

endiandricacidGmethylester

endiandricacidFmethylester

H2Lindlar

endo-DielsAlderreacZon

endiandricacidCmethylester

HH

HH CO2MePh

heat,100°C


OR

R'

OR

R'

ROH

OHR

R'

OR

R'H

Sigmatropicrearrangements.SyntheZcallythemostimportantsigmatropicrearrangementsaretheCopeandClaisenrearrangementsand

variantsthereof.TheClaisen/Coperearrangementscanproceedviachair-likeorboat-liketransiZonstates–thechair-like

transiZonstateisstronglyfavouredunlesstherearestericconstraintsthatforceaboat-liketransiZonstate.Wherepossible,subsZtuentsgenerallyadoptequatorialsitesinthechair-liketransiZonstate.

ClassicalClaisenrearrangement.

[3,3]-sigmatropicrearrangement

[3,3]-sigmatropicrearrangement

R’=H,tautomerism

tautomerism


H

H

MeMe

Me

HMe

H

ClaisenandCope

heat +

major minor

H

Me

MeH

chair

equatorial

H

Me

MeH

cis,cis-minor

chairaxial Me

HMe

H

H

Me

H

Meboat

H

Me

H

Me

trans,trans-major

cis,trans-trace


π2sπ2s

σ2s

heat

H

H

MeMe

cis,trans


OH

OEt

OEtOEt

cat.%H%%%%%%heat

O

OEt

Claisenrearrangement-variants.Johnson-Claisenrearrangement-synthesisofγ,δ-unsaturatedesters.

OEt

OEt±H+

O

OEtOEt

H

O

OEtH O

OEt O

OEt

Me

H

O

OEt

Me

H

equatorial

Eschenmoser-Claisenrearrangement-synthesisofγ,δ-unsaturatedamides.

HO

MeO

OMeNMe2

O

NMe2

O

NMe2

OMe

NMe2

heat

via

Carrollrearrangement-synthesisofγ,δ-unsaturatedmethylketones.

OHO

O

Othen%heat

IrelandClaisenrearrangement.

O

O LDA$thenMe3SiCl

O

OSiMe3O

OSiMe3

O

OH H3O+


Oxy-Coperearrangement.GenerallytheCoperearrangementrequiresveryhightemperatures>200°C.

Theanionicoxy-Copecanbeconductedatlowtemperature(0°C).

R

heat

R

OH OH O

O O OK

k1

k2

oxy-Cope

anionicoxy-Cope

k2/k1∼1010–1017

Usefulmethodforthesynthesisofcis-decalins.

MeO

O

MeO

O

HH H

H

MeO

O

H

H

MeO

O1

23

4

51

23

4

5


H H

HH

1,n-Hydrideshi�s.Asuprafacial1,n-hydrideshi�involvesthehydrogenmovingfromoneendoftheconjugatedsystemtothe

otheracrossonefaceoftheconjugatedsystem.

[1,5]suprafacialshi�ofH antarafacialshi�ofH1

1

Anantarafacial1,n-hydrideshi� involvesthehydrogenmovingfromoneendoftheconjugatedsystemtotheotherandmovingfromonefaceoftheconjugatedsystemtotheoppositeface.

2 34

5[1,7]

1

12

3

4

5 6

7

H


odd✓allowed

101

π4s

σ2s


odd✓allowed

011

π4aH

σ2a

H

π6a

σ2s


odd✓allowed

101

b

aa

ab

c

c

c

d a

a

a

b

b

c

c

c d

Bulvalene-valenceisomersinterconvertbydegenerateCoperearrangements.

b b


H

Me tBuDT

Ph

H

MetBu

DT

Ph

1,5-Hydrideshi�soccurreadilywhenthetwoendsofthedieneareheldclose.

Me H MeH

H

Me

HH

Me

HH

MeH

H

0°C

Inacyclicsystems1,5-hydrideshi�scanbemuchslower.

H

DT Me tBu

200°C[1,5]-hydrideshi�

chiralaceZcacidDPh

T

tBu

Me H

DPh

T

tBu

Me

HDPh

T

Me

H tBuO

HOT

DH

allylicstrain

disfavouredconformaZon


OMe

OMe

BuLi OMe•

• O

Me•

•OH

Me

1,2-Shi�sofalkylgroupscanalsobepericyclic.

1,2-Shi�sofcarbanionsoccurbyaradicalmechanism–1,2-Wixg,1,2-Stevensandrelatedrearrangements.

R

RR

R

RR


odd✓allowed

101

σ2s ω0s

R

R

R

R

RR

R

RRX

R

R

R


forbidden

202

ω2sσ2s

CarbocaZonsreadilyundergoallowed1,2-shi�s.

Allowed,concerted1,2-shi�sofcarbanionsaregeometricallyimpossible.

1,2-Wixgrearrangement.

O

Me

X


DHAcO

H

DHAcO

H

HD

AcO H D

AcO

Thermal[1,3]-alkylshi�soccurwithinversionofconfiguraZoninthemigraZnggroup.(4q+2)s=

(4r)a=Total=

odd✓allowed

101

π2s

σ2a

1,3-alkylshi�

HD

D HD H D H(4q+2)s=

(4r)a=Total=

odd✓allowed

101

σ2aπ2s

Inthefollowing[1,4]-shi�,migraZonoccurswithinversionofconfiguraZonwithDalwaysontheconcavefaceofthebicyclicstructure.

Thermal1,3-shi�ofhydrogenisonlygeometricallyreasonableinasuprafacialsensewhichisthermallydisallowed.

H(4q+2)s=

(4r)a=Total=even✗

forbidden

200

π2s

σ2sHHOMOσ

LUMOπ


antarafacialshi�allowedbutgeometricallyunreasonable

12

3 4

1

1

23

1

1

1 23

H

H

H H

AcO HH

D


O

ArAnumberof[2,3]-sigmatropicshi�sareusefulsyntheZcally.


odd✓allowed

303

ω2s

σ2s π2s

[2,3]-Wixgrearrangement–mostlikelyproceedsviaanenvelopetransiZonstate;largegroupsattheallylicposiZonwilltendtooccupyapseudo-equatorialposiZon.

NNMe2 Me NMe2

[2,3]

[2,3]

tautomerism

Sommelet-Hauserrearrangement.

1,5-Alkylshi�withretenZonofconfiguraZoninthemigraZnggroup.

HHheat

[1,5] [1,5]

H


odd✓allowed

101

π4s σ2s

BuLiO

ArO

ArO

Ar


A[9,9]-sigmatropicshi�.

H2N NH2 NH2 NH2

H H

NH2H2N

H2N

H2N

1

2 3

4

1

56

7

89 9

[9,9]

H2N

H2N


odd✓allowed

101

π8s

π8sσ2s

Rearrangementofallylsulfoxides,sulfiniminesandsulfoniumylids.

MeisenheimerRearrangement.

R

NO

R

ONMe2[2,3]

SX Ph

XSPh

[2,3]X=O,NTs,CH2


GrouptransferreacZons.


odd✓allowed

303

Grouptransfer–appeartobeamixofasigmatropicrearrangementandacycloaddiZon.Theyarebimolecularandsoarenotsigmatropicrearrangements,andnoringisformedsotheyarenotcycloaddiZons.

H

H

π2s

π2sσ2s

HO

OMe OMe

O

230°C

HO

OMe OMe

O

AlCl3

25°C

H

HOMOσ+π

LUMOπ


Conia-enereacZon.

O 350$°C OH

O CH3ene

tautomerise

AlderenereacZon


Carbonyl-enereacZon-frequentlycatalysedbyLewisacids.

180°C,48hSnCl4,0°C

CO2Me

CO2MeOOH

CO2MeCO2Me OHMeO2C CO2Me

922.5

897.5

CO2Me

CO2Me

O

H

OH

CO2MeCO2Me ThermalcarbonylenereacZon,sterics

areimportant.

OHMeO2C CO2Me

CO2Me

CO2Me

OH

SnCl4

IntheLewisacid-catalysedreacZonsignificantposiZvechargedevelopsinthe“eneophile”.

Retro-eneandretrogrouptransferreacZonsarecommon.

X HOR heat

+ RX

OHO H heat

+

SMeS

O HS

MeS

retro-ene retrogrouptransfer:X=S,Se,orNR(CopeeliminaZon)


PericyclicreacZonsummary:

Fourclasses:CycloaddiZons(chelotropicreacZons);ElectrocyclicreacZons;Sigmatropicrearrangements;Grouptransfer.

Woodward-Hoffmannrules:

Apericyclicchangeinthefirstelectronicallyexcitedstate(i.e.aphotochemicalreacZon)issymmetry-allowedwhenthetotalnumberof(4q+2)sand(4r)acomponentsiseven.

AgroundstatepericyclicreacZonissymmetryallowedwhenthetotalnumberof(4q+2)sand(4r)acomponentsisodd(qandrmustbeintegers).

ForthermalcycloaddiZonsandgrouptransfers:Ifthetotalnumberofelectronsis(4n+2)bothcomponentscanbeusedina

suprafacialmanner. Ifthetotalnumberofelectronsis(4n)oneofthecomponentsissuprafacialandthe

otherantarafacial.ForelectrocyclicreacZons:Thermalelectrocyclicprocesseswillbeconrotatoryifthetotalnumberofelectronsis

4nanddisrotatoryifthetotalnumberofelectronsis(4n+2).

AndjustbecauseyoucandrawapericycliccurlyarrowmechanismdoesnotnecessarilymeanthereacZonispericyclic.

pericyclic reactions 6 lectures, year 3, michaelmas...

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