pericyclic reactions 6 lectures, year 3, michaelmas...
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Pericyclic Reactions 1
Pericyclic Reactions 6 Lectures, Year 3, Michaelmas 2016
︎ ︎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
Pericyclic Reactions 2
SynopsisThenatureofpericyclicreacZons
ExamplesofpericyclicreacZons
Drawingmolecularorbitals
CorrelaZondiagrams
TheWoodward-Hoffmannrule
FronZerMolecularOrbitals
Möbius-HückelMethod
CycloaddiZons
ElectrocyclicreacZons
Sigmatropicrearrangements
GrouptransferreacZons
Pericyclic Reactions 3
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
Pericyclic Reactions 4
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.
Pericyclic Reactions 5
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+
Pericyclic Reactions 6
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
Pericyclic Reactions 7
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
Pericyclic Reactions 8
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
Pericyclic Reactions 9
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
Pericyclic Reactions 10
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
Pericyclic Reactions 11
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’
Pericyclic Reactions 12
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.
Pericyclic Reactions 13
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.
Pericyclic Reactions 14
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
Pericyclic Reactions 15
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.
Pericyclic Reactions 16
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
Pericyclic Reactions 17
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.
Pericyclic Reactions 18
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
(4q+2)s=(4r)a=Total=odd✓allowed
101
(4q+2)s=(4r)a=Total=even✗
forbidden
202
Pericyclic Reactions 19
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
(4q+2)s=(4r)a=Total=even✗
forbidden(thermally)
202
(4q+2)s=(4r)a=Total=odd✓allowed
(thermally)
101
(4q+2)s=(4r)a=Total=even✓
allowed–photochemically
202
Pericyclic Reactions 20
Nomenclatureforsuprafacialandantarafacialcomponents.
SuprafacialandantarafacialrefertomodesofbondformaZonthatarerespecZvelyonthesamefaceoronoppositefacesofamolecularcomponent.
π-suprafacial π-antarafacial
σ-suprafacial
σ-antarafacial
σ-suprafacial σ-antarafacial ω-suprafacial ω-antarafacial
C H
Pericyclic Reactions 21
MeMe
H H
MeMe
H H
MeMe
H H
Woodward-HoffmannapproachforthermalelectrocyclicreacZons
Drawa‘curlyarrow’mechanismtoidenZfythecomponents–theseare2π(alkene)and2σ(singlebond)
Drawaconvincing3-Dorbitaldiagramtoshowtheoverlapofthecomponents
Labelthecomponentsassupraorantarafacial.
SumthecomponentsaccordingtotheWoodward-Hoffmannrule.
σ2s
π2a
σ2a
π2s
π2s
σ2s
MeMeX
Thermalringopeningofcyclobuteneisconrotatory.Thermaldisrotatoryopeningissymmetryforbidden.
Me
Me
MeMe
(4q+2)s=(4r)a=Total=odd✓allowed
(conrotatory)
101
(4q+2)s=(4r)a=Total=odd✓allowed
(conrotatory)
101
(4q+2)s=(4r)a=Total=even✗
forbiddendisrotatory
202
Pericyclic Reactions 22
Me
O
Me
Woodward-Hoffmannapproachforsigmatropicrearrangements
Drawa‘curlyarrow’mechanismtoidenZfythecomponents–2π,2σ,2π
Drawaconvincing3-Dorbitaldiagramtoshowtheoverlapofthecomponents
Labelthecomponentsassupraorantarafacial.
SumthecomponentsaccordingtotheWoodward-Hoffmannrule.
Woodward-HoffmannruledoesnottellusthatthechairTSislowerinenergythantheboatTS.Youneedtouseyourchemicalknowledge/intuiZontodecidethatachairisgenerallylowerinenergythanthecorrespondingboatandthatitisgenerallymorefavourabletohaveequatorialsubsZtuentsthanaxialsubsZtuentsonachair.
ClaisenrearrangementviachairTSisallowed. ClaisenrearrangementviaboatTSisallowed.
Me
Me
O
Me
Me
O
π2s
π2sπ2s
π2s
σ2sσ2s
π2s
π2sσ2s
OOMe
Me
Me
Me
(4q+2)s=(4r)a=Total=odd✓allowed
303
(4q+2)s=(4r)a=Total=odd✓allowed
303
Pericyclic Reactions 23
O
SPh
Woodward-Hoffmannapproachforsigmatropicrearrangementsandgrouptransfer
Drawa‘curlyarrow’mechanismtoidenZfythecomponents
Drawaconvincing3-Dorbitaldiagramtoshowtheoverlapofthecomponents
Labelthecomponentsassupraorantarafacial.
SumthecomponentsaccordingtotheWoodward-Hoffmannrule.
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).
(4q+2)s=(4r)a=Total=odd✓allowed
303
(4q+2)s=(4r)a=Total=odd✓allowed
303
Pericyclic Reactions 24
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
Pericyclic Reactions 25
TheFMOapproach
AssignasingleHOMOandasingleLUMOtothereacZon
Drawaconvincing3-Dorbitaldiagramtoshowtheoverlapofthecomponents
ChecktoseeifthereisconstrucZveoverlapbetweentheorbitals
Drawa‘curlyarrow’mechanismtoidenZfythecomponents
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.
Pericyclic Reactions 26
HMe
H Me
TheFMOapproach
AssignasingleHOMOandasingleLUMOtothereacZon
Drawaconvincing3-Dorbitaldiagramtoshowtheoverlapofthecomponents
ChecktoseeifthereisconstrucZveoverlapbetweentheorbitals
Drawa‘curlyarrow’mechanismtoidenZfythecomponents
Me
MeHMe
H Me
MeMe
(4q+2)s=1(4r)a=0Total=3odd✓allowed
(conrotatory) σ2a
π2s
Thepreferenceofoneconrotatory(ordisrotatory)modeistermedtorqueoselec+vity(morelater).
HOMOalkene
LUMOalkene LUMOalkene
HOMOsigma
HMe
H MeLUMOsigma
HOMOsigma construcZveoverlap
construcZveoverlap✓
Me
Me
MeMeheat
HMe
H Me
construcZveoverlap✓
Pericyclic Reactions 27
TheFMOapproach
AssignasingleHSOMOandasingleLUMOtothereacZon,(orasingleLSOMOandHOMO)–noteaHSOMOhasthesamephasesasthe‘LUMO’andaLSOMOhasthesamephasesastheHOMO)Drawaconvincing3-Dorbitaldiagramtoshowtheoverlapofthecomponents
ChecktoseeifthereisconstrucZveoverlapbetweentheorbitals
Drawa‘curlyarrow’mechanismtoidenZfythecomponents
(4q+2)s=0(4r)a=0Total=0even✓allowed
photochemically(disrotatory)
π4s
HOMOalkene
LSOMOalkene
construcZveoverlap✓(disrotatory)
MeMe
H H
Me Mehν
Me Me
hν
Pericyclic Reactions 28
TheFMOapproach
AssignasingleHOMOandasingleLUMOtothereacZon
Drawaconvincing3-Dorbitaldiagramtoshowtheoverlapofthecomponents
ChecktoseeifthereisconstrucZveoverlapbetweentheorbitals
Drawa‘curlyarrow’mechanismtoidenZfythecomponents
(4q+2)s=1(4r)a=0Total=3odd✓allowed
Me
Me
O
π2s
π2sσ2s
ψ2
Me
Me
O
HOMObutadiene
HOMO‘π+σ’
LUMOalkene
ψ3
LUMObutadiene
Me
Me
O
LUMO‘π+σ’
HOMOalkene
construcZveoverlap✓ construcZveoverlap✓
OOMe
Me
Me
Me
Me
Me
O
Pericyclic Reactions 29
O
Ph S
O
SPh
O
SPh (4q+2)s=3(4r)a=0Total=3odd✓allowed
π2s
ω2s
σ2s
O
SPh
TheFMOapproach
AssignasingleHOMOandasingleLUMOtothereacZon
Drawaconvincing3-Dorbitaldiagramtoshowtheoverlapofthecomponents
ChecktoseeifthereisconstrucZveoverlapbetweentheorbitals
Drawa‘curlyarrow’mechanismtoidenZfythecomponents
HOMOalkene
LUMO,σ+ωHOMOω
LUMO,alkene+σ
ψ3
LUMObutadiene
ψ3
LUMO4e-allyl
construcZveoverlap✓ construcZveoverlap✓
SO Ph
OSPh
Pericyclic Reactions 30
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
Pericyclic Reactions 31
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
Pericyclic Reactions 32
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%
Pericyclic Reactions 33
•
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
Pericyclic Reactions 34
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.
Pericyclic Reactions 35
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
Pericyclic Reactions 36
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
Pericyclic Reactions 37
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.
Pericyclic Reactions 38
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
Pericyclic Reactions 39
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
Pericyclic Reactions 40
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)
Pericyclic Reactions 41
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
Pericyclic Reactions 42
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
(4q+2)s=(4r)a=Total=odd✓allowed
101
ω0s
Pericyclic Reactions 43
OO
O
OC
C
OC
C
CycloaddiZonsKeteneFronZerOrbitals
HOMO(C=Cπ)
LUMO(C=Oπ*)
LUMO+1(C=Cπ*)
HOMOalkene
LUMO+1ketene
construcZveoverlap✓
HOMOalkene LUMOalkene
LUMOketene HOMOketeneWithketenesitisprobablethatthelowlyingC=Oπ*orbitalisinvolvedinthereacZon.
• OH
H OHH
Othercumulatedπsystemswhichcontainacentralsp-hybridisedcarbonatom(e.g.allenes,vinylcaZons)alsoreadilyundergo[2+2]cycloaddiZon.
OC
C
Pericyclic Reactions 44
•
Cl
H
O O •Cl
H
•Cl
H
O
Withanunsymmetricalketene,thelargerketenesubsZtuentwillpointawayfromtheplaneofthealkene.
CycloaddiZons
HOMOdiene
LUMO+1ketene
construcZveoverlap✓
InreacZonsofunsymmetricalalkenesthelessstericallydemandingC=OpartoftheketenewillbeorientedabovethelargeralkenesubsZtuents.
Ketenesreadilyreactwithcyclopentadienetogivecyclobutanes.
(4q+2)s=(4r)a=Total=odd✓allowed
101
RegioselecZvitycanbepredictedfromsimple“arrow-pushing”arguments(theC=Ocarbonofketenesisveryelectrophilic),orfromlookingatFMOcoefficients.
•O
Cl H
H
H
O
Cl
Cl
H
O
π2s
π2a
Pericyclic Reactions 45
•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=
(4r)a=Total=odd✓allowed
101
π2s
π4s
HOMOdiene
LUMOketene
σ2sπ2s
π2s
•
HCl
O
HCl
O
Pericyclic Reactions 46
Oxyallyl-diene
construcZveoverlap✓disrotatory
(4q+2)s=(4r)a=Total=odd✓allowed
disrotatory
101
HOMOsigma
LUMOω
σ2s
ω0s O
O OO
O
OO O
O
HOMOdiene
LUMOallylcaZon
construcZveoverlap✓
O
(4q+2)s=(4r)a=Total=odd✓allowed
101
π2s
π4s
Pericyclic Reactions 47
Ph
Ph
Ph
Br
AgBF4
Ph
Ph
Ph
Allylanion-alkeneandreverseprocess
AllylcaZon-diene
HOMOallylanion
LUMOalkene
construcZveoverlap✓
(4q+2)s=(4r)a=Total=odd✓allowed
101
π2s
π4sπ2s
Ph
H
LDA,%45%°C
PhPh
PhPh
Ph
Ph
HPh
Ph
Ph
π4s
Pericyclic Reactions 48
Ph
OO
O
O
O
O Ph
H O
OPh
BuLi+ PhCO2
Allylanion-alkene(reverseprocess)
HOMOω
LUMOσ+σ
construcZveoverlap✓(4q+2)s=
(4r)a=Total=odd✓allowed
303
σ2s
σ2s ω2s
ψ3
LUMObutadiene
O
O
HOMOcarboxylate
LUMOalkene
construcZveoverlap✓
ItcanbeeasiertoanalysethereversereacZon.
PhO
O
O
OPh
Pericyclic Reactions 49
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
Pericyclic Reactions 50
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
Pericyclic Reactions 51
Ozonolysis
OO
O
OO
O
π4s
π2s(4q+2)s=
(4r)a=Total=odd✓allowed
101
OO
O
HOMOalkene
LUMOozone
ψ3
LUMOallylanion
construcZveoverlap✓
OO
O
OO
O
HOMOcarbonylLUMOcarbonyl
construcZveoverlap✓
OO
C
O
HOMOcarbonylylid
construcZveoverlap✓
LUMOcarbonylylid
•ψ2
HOMOallylanion
OO
O
OO
O
ω2sσ2sσ2s
Pericyclic Reactions 52
Azomethineylids.
σ2s
ω2a
(4q+2)s=(4r)a=Total=odd✓allowed
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]
Pericyclic Reactions 53
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
Pericyclic Reactions 54
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
Pericyclic Reactions 55
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
Pericyclic Reactions 56
O
CheletropicReacZons
Asub-classofcycloaddiZon/cycloreversionreacZonsinwhichthetwoσ–bondsaremadeorbrokentothesameatom.
O
CO+
MoreimportantarethereacZonsofsingletcarbeneswithalkeneswhicharestereospecific.
Cl
Cl
MeMe
MeMe
Cl Cl
Cl Cl
π2s
ω0a
ω2s(4q+2)s=
(4r)a=Total=odd✓allowed
213
Cl
Cl
LUMOalkene
HOMOcarbene
construcZveoverlap✓
Cl
ClLUMOcarbene
HOMOalkene
construcZveoverlap✓
SideonapproachofthecarbeneisrequiredforconservaZonoforbitalsymmetry.
π2s
π2a
ω0s
(4q+2)s=(4r)a=Total=odd✓allowed
101
c.f.ketenesasvinylcaZons
Cl Cl
•
O
Cl Cl
•
OO
R
R
ClCl
R R
Pericyclic Reactions 57
O
S O
CheletropicReacZons
TheotherimportantcheletropicreacZonsinvolvethereversibleaddiZonofsulfurdioxidetopolyenes.
ω2s (4q+2)s=(4r)a=Total=odd✓allowed
101
LUMOdiene
HOMOSO2
construcZveoverlap✓
LUMOSO2
HOMOdiene
construcZveoverlap✓
SO2SO2
SO2SO2
π4sO
S O
O
S OHOMO–lonepair
LUMO
O
S O
O
S O
heatandpressure
heatandpressure
Pericyclic Reactions 58
SO2
heatSO2
heat
%&SO2%&SO2
OS
O
OS
O
CheletropicReacZons
WithtrienestheextrusionprocessdominatesbutconsideringthereverseprocessthereacZonmustbeantarafacialwithrespecttothetrienecomponent.
ω2s
(4q+2)s=(4r)a=Total=odd✓allowed
101
LUMOtriene
HOMOSO2
construcZveoverlap✓
LUMOSO2
HOMOtriene
construcZveoverlap✓
π6a
HOMO–lonepair
LUMO
OS
O
SO O
X toostrained;ca.104ZmeslessreacZvethan SO2
LUMOhexatriene
Pericyclic Reactions 59
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
Pericyclic Reactions 60
MeMe
Me
Me
Me
Me
Me
Me
ElectrocyclicreacZons
Thermalelectrocyclicprocesseswillbeconrotatoryifthetotalnumberofelectronsis4nanddisrotatoryifthetotalnumberofelectronsis(4n+2)–thisisreversedforphotochemicalreacZons.
AllelectrocyclicreacZonsareallowed(providedtheyarearenotconstrainedbythegeometryoftheproduct).
(4q+2)s=(4r)a=Total=odd✓allowed
disrotatory
101
MeMe
π6s
HMeMe
(4q+2)s=(4r)a=Total=odd✓allowed
disrotatory
101
π6s
140°C,5h 140°C,5h
Me MeH HH
Me
H
Me
(4q+2)s=(4r)a=Total=odd✓allowed
conrotatory
101X
butgeometricallyconstrainedthereforedoesnotoccur.
H H
MeMe
π2a
σ2s
Pericyclic Reactions 61
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
construcZveoverlap✓conrotatory
CyclopropylcaZon/allylcaZoninterconversion
TheionisaZonofcyclopropylhalidesandtosylatesisaconcertedprocesstogiveallylcaZons(i.e.discretecyclopropylcaZonsarenotformed).
ThereacZoncanbeviewedasaninternalsubsZtuZoninwhichtheelectronsinaσ-bond(HOMO)feedintotheC-Xσ*(LUMO).
ThereacZonisdisrotatoryandthesenseofrotaZon(torquoselecZvity)isspecified–thisdictatesthegeometryoftheallylcaZonandcanhavealargeinfluenceonreacZonrate.
Cl Cl Cl
Lewisacidlowtemperature
ψ2
ψ1
ψ3
•
Pericyclic Reactions 62
Cl
H
H
Me
Me
Cl
Me
Me
H
H
ElectrocyclicreacZons
(4q+2)s=(4r)a=Total=
odd✓allowed
disrotatory
101
ω0sHOMOσ
LUMOσconstrucZveoverlap✓disrotatory
Cl
Me
H
H
Me
construcZveoverlap✓disrotatory
Cl
H
H
Me
Me
Cl Cl Cl
construcZveoverlap✓disrotatory
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
Pericyclic Reactions 63
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
construcZveoverlap✓conrotatory
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
Pericyclic Reactions 64
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.
Pericyclic Reactions 65
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
Pericyclic Reactions 66
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
Pericyclic Reactions 67
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
Pericyclic Reactions 68
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
(4q+2)s=3(4r)a=0Total=3odd✓allowed
π2sπ2s
σ2s
heat
H
H
MeMe
cis,trans
Pericyclic Reactions 69
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+
Pericyclic Reactions 70
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
Pericyclic Reactions 71
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
(4q+2)s=(4r)a=Total=
odd✓allowed
101
π4s
σ2s
(4q+2)s=(4r)a=Total=
odd✓allowed
011
π4aH
σ2a
H
π6a
σ2s
(4q+2)s=(4r)a=Total=
odd✓allowed
101
b
aa
ab
c
c
c
d a
a
a
b
b
c
c
c d
Bulvalene-valenceisomersinterconvertbydegenerateCoperearrangements.
b b
Pericyclic Reactions 72
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
Pericyclic Reactions 73
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
(4q+2)s=(4r)a=Total=
odd✓allowed
101
σ2s ω0s
R
R
R
R
RR
R
RRX
R
R
R
(4q+2)s=(4r)a=Total=even✗
forbidden
202
ω2sσ2s
CarbocaZonsreadilyundergoallowed1,2-shi�s.
Allowed,concerted1,2-shi�sofcarbanionsaregeometricallyimpossible.
1,2-Wixgrearrangement.
O
Me
X
Pericyclic Reactions 74
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
construcZveoverlap✓
antarafacialshi�allowedbutgeometricallyunreasonable
12
3 4
1
1
23
1
1
1 23
H
H
H H
AcO HH
D
Pericyclic Reactions 75
O
ArAnumberof[2,3]-sigmatropicshi�sareusefulsyntheZcally.
(4q+2)s=(4r)a=Total=
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
(4q+2)s=(4r)a=Total=
odd✓allowed
101
π4s σ2s
BuLiO
ArO
ArO
Ar
Pericyclic Reactions 76
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
(4q+2)s=(4r)a=Total=
odd✓allowed
101
π8s
π8sσ2s
Rearrangementofallylsulfoxides,sulfiniminesandsulfoniumylids.
MeisenheimerRearrangement.
R
NO
R
ONMe2[2,3]
SX Ph
XSPh
[2,3]X=O,NTs,CH2
Pericyclic Reactions 77
GrouptransferreacZons.
(4q+2)s=(4r)a=Total=
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
construcZveoverlap✓
Conia-enereacZon.
O 350$°C OH
O CH3ene
tautomerise
AlderenereacZon
Pericyclic Reactions 78
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)
Pericyclic Reactions 79
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.