Page 1
Rearrangements and Reactive Intermediates
1
Rearrangements and Reactive Intermediates
Hilary Tem 2017
1A Organic Chemistry
Handout 1
h"p://burton.chem.ox.ac.uk/teaching.html
︎ ︎PolarRearrangements,OxfordChemistryPrimerno.5;L.M.Harwood︎OrganicChemistryJ.Clayden,N.Greeves,S.Warren–Chapters36-41Reac4veIntermediates,OxfordChemistryPrimerno.8;C.J.Moody,G.H.Whitham
MechanismandTheoryinOrganicChemistry,T.H.Lowry,K.S.RichardsonAdvancedOrganicChemistry,F.A.Carey,R.A.SundbergModernPhysicalOrganicChemistry;E.Anslyn,D.Docherty
Me Me
MeHO
H Me
Me
1
23
4567
8
12
4 56
7
8
3
isoborneol
[email protected]
camphene
Page 2
Rearrangements and Reactive Intermediates
2
Carboca'onsandcarbanionsNMRspectroscopyandX-raystructuresofcarbocaZons;aggregaZonandpyramidalinversionofcarbanions.ReacZvity,includingSE1,redox,hydrideeliminaZonandrearrangements:Wagner–Meerwein,pinacol,semi-pinacol.
Rearrangementofanionsandcarboca'onsOrbitaltheory;Is3c-2estructureTSorHEI?Stepwiseversusconcertedrearrangements;non-classicalcarbocaZons(carboniumions),transannularhydrideshi`s.Carbanions:Favorskii,Ramberg-Bäcklund,StevensandWicgrearrangements.
CarbenesStructuralfeaturesthatinfluencestability.Methodsofmakingthem;carbenesversuscarbenoids.GeneralclassificaZonofthetypesofreacZonthatthesespeciesundergo.Rearrangements:Wolff,cyclopropanaZon,C-HinserZon.
Rearrangementstoelectron-deficientnitrogenandoxygenStructureofnitrenes;structuralfeaturesthatinfluencestability.Methodsofmakingthem.TypesofreacZon:aziridinaZon,C–HinserZon.Nitreneversusnon-nitrenemechanisms.Rearrangementstoelectron-deficientnitrogen(Beckmann,Neber,Hoffmann,CurZus,Schmidt,Lossen).Baeyer–Villigerrearrangement.
Introduc'ontoradicalsStructure;stability.GeneraltypesofreacZoninvolvingradicals:homolysis,recombinaZon,redox,addiZon,β-scission,subsZtuZon,disproporZonaZon.
ProblemclassrelaZngtolectures1–4.
CasestudiesElucidaZngmechanismsofrearrangements.EvidenceforcurrentlyacceptedmechanismsfortheBaeyer–Villiger,BeckmannandFavorskiirearrangements.
ProblemclassrelaZngtolectures5and7.
Synopsis
Page 3
Rearrangements and Reactive Intermediates
3
R
R ••
R
R
R
R
RR ••
RR
RRR
ElectronDeficientCaZonsTwoclassesofcarbocaZons
Carbeniumion(6electrons)
Carboniumion(8electrons)
RadicalcaZon
CH5
ElectronRichAnionsCarbanion(8electrons)
RR
R
RR
R••
RRR
TypesofHighEnergyIntermediates
NeutralspeciesRadical(7electrons)
RR
R•
tripletsinglet
H
H
H
HH
H• +
•
HH
HH
H
H
H
H
H
HH
H •
HH
HH
H
H
ElectronRichAnionsRadicalAnion
NeutralspeciesCarbenes(6electrons)
reac4vetowardsa) nucleophilesb) basesc) reducingagents
e.g.
reac4vetowardsa) electrophilesb) acidsc) oxidisingagents
reac4vetowardsa) electrophilesornucleophilesb) otherhighenergyagentsc) oxidisingorreducingagents
Neutralspeciesketenes
• OR
R
NeutralspeciesArynes
Page 4
Rearrangements and Reactive Intermediates
4
Me
Me
Me
BondlengthsandbondanglesprovideevidenceofhyperconjugaZon(T.Laube,Angew.Chem.Int.Ed.1986,25,349).
CrystalstructureofanadamantylcarbocaZon
F5SbFSbF5
1.44Å
1.62Å
1.52Å
118°
99°
111°
1.53Å
110°
adamantane
Me
Me
Me Me
Me
MeMe
Me
Me
Me
Me
Me
Me
MeMe
F
2SbF5
SO2
δC294ppmδC71ppm
δC90ppm
δC30ppm
δC49ppm
C-C sp3-sp3 1.54Å
C-C sp3-sp2 1.50Å
C-C sp2-sp2 1.46Å
C=C 1.34Å
δC38ppm
δC29ppm
StucturesofCarboca'ons
Page 5
Rearrangements and Reactive Intermediates
5
Crystalstructureofat-butylcarbocaZon
F5SbFSbF5
C-C sp3-sp3 1.54Å
C-C sp3-sp2 1.50Å
C-C sp2-sp2 1.46Å
C=C 1.34Å
H HH
H
HH
H
HH
1.44Å
120°
BondlengthsprovideevidenceofhyperconjugaZon(T.Laube,J.Am.Chem.Soc.1993,115,7240).
F
H3C CH3CH3
2SbF5
SO2
CH3
H3C CH3
O
FH3C
CH3H3C
2SbF5
SO2
δC=335ppm
δC=47ppm δH=4.35ppm
SbF5
SO2
H
H3C CH3
F
H3C CH3δH=5ppm
δH=13.5ppm
δC=51.5ppm
δC=320ppm
δC=94ppm
δC=28ppm δC=171ppm(adamantylacidfluoride)
Page 6
Rearrangements and Reactive Intermediates
6
R R > R R > Rtertiary secondary primary
R
filled σ C-H orbital
empty p-orbital
energyofthebondingelectronsreducedsystemstabilised
greaternumberofC-H(orC-C)σ-bondsthegreatertheextentofhyperconjugaZonandthegreaterstabilisaZon
CH3
CH3
H
HH
donaZonofC-Hσ-bond(orC-Cσ-bond)electronsintoemptyporbital
carbeniumionstabilitythereforegoesintheorder:
conjugaZonwithalkenes,arenesandlonepairs,alsostabilisescarbeniumions
mostcarbocaZonsarefleeZngreacZonintermediates–thetriphenylmethyl(trityl)caZonpersists-crystalstructureoftritylcaZondemonstratesallthephenylgroupsaretwistedoutofplane
B(CN)4
OHPh
PhPh
H2SO4
CH2Cl2
HSO4
HyperconjugaZon
δC=212ppm
Ph3CBF4isacommerciallyavailablecrystallinesolid
Page 7
Rearrangements and Reactive Intermediates
7
generallyaggregatedinthesolidstateandinsoluZon
StructuresofCarbanions
methyllithiumisatetramer(MeLi)4withCH3groupssicngaboveeachfaceofaLi4tetrahedron—overalladistortedcube
tert-butylliZumisalsotetramericinthesolidstate(X-raycrystalstructuresbelow)
Li
C
C
Li
C
Li
Li
C
methyllithium(MeLi)4
(H-atomsremovedforclarity)
t-butyllithium(t-BuLi)4
incoordinaZngsolventse.g.THF,Et2OmostorganolithiumsbecomelessaggregatedandhencemorereacZve
idealisedarrangementoflithiumandcarbonatoms
Page 8
Rearrangements and Reactive Intermediates
8
H
H
H
HH
H
HH
H
H
H
H
H
H H HH H Me
H Me MeH Me Me
Me
CH3 CH3CH2 (CH3)2CH (CH3)3C
stabilityofcarbanionsisrelatedtothepKaoftheirconjugateacids
increasingpKaofconjugateacid,increasingreacZvity,decreasingstability
16 24 41 43 44
46 48 50 51 53
aromaZc sp-hybridised conjugated sp2-hybridised sp2-hybridised
sp2-hybridised sp3-hybridisedsp3-hybridisedelectrondonaZngalkylgroup
sp3-hybridisedelectrondonaZngalkylgroups
sp3-hybridisedelectrondonaZngalkylgroups
increasingpKaofconjugateacid,increasingreacZvity,decreasingstability
Page 9
Rearrangements and Reactive Intermediates
9
PhBr
PhLi
RBr
Ph RtBu Li
sp2hybridisaZonattransiZonstateforpyramidalinversionideal120°anglesonlyca.60°forcyclopropanetransiZonstatehighlystrained
thereforeslowrateofinversion
pyramidalinversionisgenerallyfastforsp3hybridisedcarbanions(theyareisoelectronicwithNH3)andhencechiralcarbanionsgenerallyundergorapidracemisaZon.
R
‡
vinylanionsandcyclopropylanionsaretheexcepZonsandaregenerallyconsideredconfiguraZonallystable
lithiumhalogenexchangewithalkenyliodidesandbromidesisastereospecificprocess
BrMe
Ph Ph
BuLiLiMe
Ph Ph(S)
CO2HMe
Ph Ph
CO2
retention
RR'R'' R R''
R'fast
RR'R''
‡
BrtBuLi
LiR
BrR
Ph Ph Ph
Page 10
Rearrangements and Reactive Intermediates
10
RH
- H
Reac'onsofCarboca'onsandCarbanions
GenericreacZonmapofcarbocaZonsandcarbanions
R RR•
+ e
- e
+ e
- eR
X - X
SN1 or E1
R
E
Nu
RNu
R
- H
RX- X
SE1
R
R
- H
RH
- H
RR
X
+ 2e
RE
E
carbocaZonrearrangement
hydrideloss
ionisaZon
deprotonaZon
reacZonwithnucleophile
singleelectrontransfer(SET)
SET
electrophilereacZon
reducZondeprotonaZon
carbanionaddiZonhydrideloss
reacZonwithelectrophile
electrophilicsubsZtuZon
Page 11
Rearrangements and Reactive Intermediates
11
NR
R N
R
R
ROH R
RH
- N2
OP
PhPh
OH, H2O
heat
OP
O PhPh
H+
OP
HO PhPh +
mostcommonreacZonofcarbanionsisreacZonwithelectrophiles(e.g.RLiorRMgBrplusE⊕)whichisamplycoveredelsewhere
someotherreacZonsareshownbelow
SE1– SubsituZonElectrophilicUnimolecular-formallyrelatedtoacarbanionasSN1istoacarbocaZon
genericmechanism
RRX - X
SE1
ER
E
examples
OPPhPh
HO
Ph
OH
Ph
OOH O
Ph Ph
OBr
Br Br
Page 12
Rearrangements and Reactive Intermediates
12
β-hydrideeliminaZonfromcarbanionscommonfortransiZonmetals
PdXH
+ HPdX
reversereacZonishydrometallaZon–wellknownfromhydroboraZonchemistry
HBR2 BR2
H
notacommonreacZonforGrignardreagentsororganolithiums;however,β-hydrideeliminaZonisadecomposiZonpathwayfororganolithiumsandtert-butyllithiumcanactasasourceofhydride
HLi
MeMe
Me
Me+ LiH
redoxreacZons–SingleElectronTransfer-SET
MgBr+
ClCl •
H
H
HH+
SET
• ClCl•+
dimerisationof Ph•
Cl
•
SETCl
Page 13
Rearrangements and Reactive Intermediates
13
MeLG
HHNu
NuR'R'' LG
H H
LGNu(-) (-)
‡Me
Me Me MeMe
MeMeMe
rearrangementofcarbocaZons
Me
MeMe
I
AgNO3, water
Me
Me MeHO
Me
Me Menot
Me
MeMe
OH+
Ag
Me
MeMe
theneopentylsystem
asanaside,rememberthatneopentylsystems,althoughprimary,areunreacZveunderSN2condiZonsasthenucleophileisseverelyhinderedfroma"ackingthenecessarycarbonatom
Me
Me Me1,2- shift
H2Othen - H - H
the1,2shi`isaWagner-Meerweinrearrangement
staggeredconformaZonrequiresnucleophiletoapproachpassedoneofthemethylgroups
Page 14
Rearrangements and Reactive Intermediates
14
MeMe
MeH
1
2
3
456
8
7
Me Me
Me
H
1
2
3 4
5
67
8
Me Me
Me
1
23
4567
8
Wagner-MeerweinrearrangementsexemplifiedMe Me
MeHO
H Me
Me
1
23
4567
8
Me Me
MeH2O
1
23
4567
8
H
Me Me
Me
1
23
456
7
8rotate
Me MeMe1
2
34
567
8
rotate
Me
MeMe
12
4 56
7
8
3- H12
4 56
7
8
3
overallredbondisbrokenandbluebondisformed
bestorbitaloverlapisalsoimportantindeterminingwhichgroupmigrates
secondarycarbocaZon
terZarycarbocaZon
1
23
456
7
8
MeMe
Me
orbitaloverlapσC-Cintoemptyp-orbital
Me Me
Me
1
23
4567
8
ingeneralalkylshi`soccurtoyieldamorestablecarbocaZon
bestorbitaloverlapformigraZon(ca.co-planar)
poororbitaloverlapformigraZonmigraZon
wouldleadto4-memberedring
isoborneol camphene
Page 15
Rearrangements and Reactive Intermediates
15
OMe
Me
Me
Me
MeMeH
HH
Me Me
HHO
Me
Me
MeMe
MeH
Me H
Me
Me
pyrophosphate,ordiphosphate–PPO.PPOisagoodleavinggroupc.f.TsO
Me Me
MeOPO
P
OOO
O
O
Me
Me
12
4 56
7
8
3- H
Wagner-Meerweinrearrangementsexemplified–Naturewasherebeforeus–biosynthesisofcampheneMe Me
Me
- OPP
Me
MeMe 1
2
45
6
7
8
3
Me
MeMe
12
456
7 8
3
Me Me
Me
1
23
4567
8
Me Me
Me
1
23
4567
8
Me Me
Me
1
23
456
7
8
Me
MeMe
12
4 56
7
8
3
form3°caZon form3°caZon form2°caZonreliefofringstrain
Wagner-Meerweinrearrangementsexemplified–Naturewasherebeforeus–biosynthesisoflanosterol(precursororcholesterol)
HO
Me
Me
Me
Me
Me
H
MeH
H H
Me Me
squaleneoxide lanosteroltwo1,2-hydrideshi`stwo1,2-methylshi`s
chair–boat–chairconformaZon
conformaZonofsqualeneoxidecontrolledbyenzyme(lanosterolsynthase)–reacZonoccursviadiscretecarbocaZonintermediatesandisnotconcerted
H
linalylpyrophosphate
Page 16
Rearrangements and Reactive Intermediates
16
mechanisminmoredetailcorrectorbitaloverlaprequiredformigraZon
Me
Me
Me
HO Me
H2O OHHO
- H
Pinacolandsemi-pinacolrearrangements
HO OH
MeMe Me
MeH
O
MeMe
MeMe
HO OH2
MeMe Me
Me
H
Me
MeHO
MeMe
OH
MeMe
MeMe
H CH3CH3
Me
OH
CH3CH3
Me
HOH
nOtoσ*C-C
σC-Ctoemptyp
usefulmethodforthepreparaZonofspirocyclicketones.
OH
HO H
OH
H2O
OH OOH
-H
pinacol pinacolone
thestarZngdiolscanbereadilypreparedbythepinacolreacZon
O Mg
SET
O
•Mg2
O OMg
• •
OMg
O
epoxidesandhalohydrinscanbesubstratesforthepinacolrearrangement
Page 17
Rearrangements and Reactive Intermediates
17
tBuO
N2
H
H
tBuH
N2
O
H
tBuO
H
H
N2
tBuH
H
OH
N2
tBu NH2
OH
tBu NH2
OH
tBu NH2
OH
tBu NH2
OH
HNO2
HNO2
HNO2
HNO2
H
C
H
H
H
H
H
semi-pinacolrearrangements–theTiffeneau-DemayanovreacZon
HOHNO2
NH2HO
N2 OH O
- HO i) CN
ii) LiAlH4or
i) CH3NO2. EtOii) LiAlH4
semi-pinacolrearrangements-stereochemistry
anZ-periplanarbondsmeansbestoverlapofσandσ*orbitals
tBu O
H
H
C-Cmigration
H
tBu O
H
H
C-Cmigration
H
tBu
O
H
H
1,2-hydrideshift
H
tBuH
H
Oepoxideformation
H
σC-Ctoσ*C-N
σC-Ctoσ*C-N
σC-Htoσ*C-N
nOtoσ*C-N
tBuO
H
tBuO
H
tBu
O
tBuO
nOtoσ*C-C
nOtoσ*C-C
nOtoσ*C-H
Page 18
Rearrangements and Reactive Intermediates
18
OH
Me Me
O
Me Me
thedienone-phenolrearrangement–formallythereverseofthepinacolrearrangement
OH
Me Me
H
OH
Me
MeH
OH
MeMe
thepinacolrearrangementisdrivenbyformaZonofastrongC=Obond
thedienone-phenolrearrangementinvolveslossofaC=ObondandgainofanaromaZcring
thedienone-phenolrearrangementcanbemechanisZcallycomplexbutcanalsojustinvolveasimple1,2-shi`ofanalkylgroup
Cl
OHtBuO
Cl
O O
H
OH
thedienone-phenolrearrangementprovidesamethodforringannulaZon
Page 19
Rearrangements and Reactive Intermediates
19
R
R
C
R
R
R
R
R
R
R
R
C
R
R
C
R
RR
R
R
R
R
R
R
RR
R
R'''
R''R'
R''' R''R' R'''
R''
R'
Theoryof1,2-shiHscurlyarrowmechanism
orbitaldescripZon
3-centre-2-electronsystematthetransiZonstate
inthetransiZonstatewehavethreeorbitalsandtwoelectronstodistributec.f.theallylcaZon
•
ψ1
ψ2
ψ3
allylcaZon 1,2-shi`transiZonstate(carbocaZon)
R
R
R
R
R
R
R
R
R
R
R
R
ψ1
ψ2
ψ3
R
R
R
R
R
R
R
R
R
R
R
R
ψ1
ψ2
ψ3
1,2-shi`transiZonstate(carbanion)
retenZon retenZon
Page 20
Rearrangements and Reactive Intermediates
20
1,2-caZonand1,2-anionshi`soverallforcarbocaZon1,2-shi`,transiZonstatehasnetbonding
thetransiZonstatehas2electronscyclicallyconjugatedinaringandisthereforearomaZc–moreofthisnextyear
bothψ2 andψ3areanZbonding
therefore1,2-shi`sofcarbanionsandradicalswouldbeexpectedtobefarlessfavourable(ψ2isoccupied)
transiZonstatefor1,2-shi`ofcarbanionshas4electronscyclicallyconjugated(ψ1
2ψ22)inaringandisanZ-aromaZc
takehomemessage–1,2-shi`seasyforcarbocaZons,difficultforcarbanionsandradicals
R
R
R
R
R
R
R
R
R
R
R
R
ψ1
ψ2
ψ3
R
R
R
R
R
R
R
R
R
R
R
R
ψ1
ψ2
ψ3
1,2-shi`transiZonstatecarbanion
1,2-shi`transiZonstatecarbocaZon
1,2-shi`soccurwithretenZonofconfiguraZoninthemigraZnggroup
the3-centre-2-electronstructuremaybeatransiZonstateorahighenergyintermediate
aswehaveseen,concertedmigraZonwithlossoftheleavinggroupisanothermechanisZcpossibility
onecanalsoviewthedifficultyof1,2-carbanionshi`sarisingfromthegeometricalimpossibilityofthecarbanionperforminganintramolecularSN2reacZonwithinversionofconfiguraZon R
RR
R
R'''
R''R'
Page 21
Rearrangements and Reactive Intermediates
21
HH H
H
H
aswehaveseen,forefficientrearrangementorbitalalignmentiscriZcal
retenZonofconfiguraZonatthemigraZngcentreisobserved
allthreeindicatedhydrogenatomsareinthesameplane-rearrangementtothemorestable3°carbocaZondoesnotoccur
Me
Me MeNH2
Me
HNO2Me
Me MeN2
Me
Me
Me
MeMe
Me
Me
MeMe
HOH2O
migraZonwith98%retenZonofconfiguraZon
atthemigraZngterminusinversionorracemisaZoncanoccur
MeEtHO OH H
MeEtH2O OH Et
Me H
OH Et
Me H
OH
enanZopure racemic
racemisaZonwilloccurifthemechanismisSN1-likei.e.viaafullcarbocaZon
inversionatthemigraZngterminuswilloccurifthemechanismisconcerted
Page 22
Rearrangements and Reactive Intermediates
22
Br
BrMeH
HMe
Br
Br HMe
Me H
Br
BrMeH
MeH
Br
Br MeH
Me H
ConcertedRearrangements
NeighbouringgroupparZcipaZon(NGP)
DefiniZon(IUPAC):thedirectinteracZonofthereacZoncentre(usually,butnotnecessarily,anincipientcarbeniumcentre)withelectronscontainedwithintheparentmoleculebutnotconjugatedwiththereacZoncentre–couldbelonepair,π-bond,orσ-bondArateincreaseduetoneighbouringgroupparZcipaZonisknownas'anchimericassistance’neighbouringgrouppar4cipa4onandanchimericassistanceareoKenusedinterchangeably
Br
OHMeH
MeH HBr
Br
OHMeH
HMe HBr
Br
OH2MeH
MeH
MeH
Br
MeH
Br
Br
OH2MeH
HMe
MeH
Br
HMe
Br
diastereomericsingleenanZomerbromohydrins
meso
C2symmetric
enanZomerssamerelaZveconfiguraZonasstarZngmaterialracemicproduct
samestructuremeso-achiral
outcomeofabovereacZonsisexcellentevidenceforsymmetricalintermediatesandhenceneighbouringgroupparZcipaZon
inversioninversion
inversioninversion
Page 23
Rearrangements and Reactive Intermediates
23
alternaZveperspecZveofNGP
TsO
H
7
12
3
45
6
whydothesesingleenanZomertosylatesundergosolvolysisatsignificantlydifferentratestogiveracemicproduct? non-classicalcarbocaZons,A.K.A.carboniumions
OTs
HAcOH
OAc AcO
H H
+ OTs
H
AcOH
1 2
34
56
7
O
Me OH
AcO
HOAc
H
AcO
H
rdsNGP
krel=350krel=1
AcO
H
1.8Å
3-centre-2-electronbonds
O
Me OH
rdsnoNGP
exo-TsreactsfasterduetoNGPofanZperiplanarC-Csigmabondendo-TsionisesslowertogiveclassicalcarbocaZon
followedbynon-classicalcarbocaZonformaZonnon-classicalcaZonhasplaneofsymmetryleadingto
racemicproducts
exo-Tsendo-Ts
non-classicalcarbocaZon-carboniumion
racemic
Page 24
Rearrangements and Reactive Intermediates
24
MeMe
Me Me
evidencefornon-classicalcarbocaZon(carboniumion)overequilibraZngcarbeniumionsforthe2-norbornylcaZoni.e.isthenon-classicalcaZonanintermediateorTS?
lowtemperature13CNMR(5K)showsasymmetricalion
X-raycrystalstructure(Science,2013,341,62)provideddefiniZveevidenceofbridgedstructure
1.8Å
δC125ppm
Note:non-classicalcarbocaZonsareonlyformediftheyaremorestablethantheirclassicalcounterpartsBr3AlBrAlBr3
The1,2-dimethylnorbornylcaZonisarapidlyequilibraZngspecieswithparZalσ-delocalisaZon.
X-raystructureoftheanalogoustetramethylnorbornylcaZonalsodemonstratesparZalσ-delocalisaZon.
Me Me
Me
Me
1.7Å2.1Å
F5SbFSbF5
Page 25
Rearrangements and Reactive Intermediates
25
J
H
H
OAc
AcOH
OTsAcOH
π-bondsarebe"erdonorsthanσ-bonds
TsO HO
Me
HOAcO OAc
TsOO
Me
HO AcO
OTs
H
HHH
krel=1
krel=1011
krel=104
krel=107
SbF6 SbF6
Ph
Me
Me
classicalcarbocaZon(carbeniumion)
non-classicalcarbocaZon(carboniumion)
allylcaZon
J.Am.Chem.Soc.,1989,111,9224
completeretenZonofconfiguraZon(doubleinversion)
samestructure
Page 26
Rearrangements and Reactive Intermediates
26
OAcHMe
HMe
AcO HMe
H Me
MoreneighbouringgroupparZcipaZonwithπ-bonds– phenoniumions
OTsHMe
HMeAcOH
HMe
HMe
O
Me OH
OTsHMe
MeHAcOH
HMe
MeH
O
Me OH
OAcHMe
MeH
AcO MeH
H Me
enanZomersracemicproduct
diastereomericsingleenanZomer
substrates
mesophenoniumion(σ-plane)
C2-symmetricphenoniumion
samesingleenanZomerproduct
69ppm
δC=60ppm
172ppm
133ppm155ppm
inversion
inversion
inversion
inversion
Page 27
Rearrangements and Reactive Intermediates
27
H2, Pd
MeMe
Br AlBr3
heat
H2O
- H
mulZple1,2-shi`s
OHMe
H
MeHO
Me
- H2OH
Me Me Me
MeMe
formaZonofadamantane
Diels-Alder
C10H16 adamantaneC10H16allC10H16hydrocarbonsrearrangetoadamantaneontreatmentwithLewisacid
adamantaneisthethermodynamicallymoststableC10H16isomer–itpossessrepeaZngunitsofthediamondlacce
Page 28
Rearrangements and Reactive Intermediates
28
Cl
SbF5, FSO3F
-140 °Cor or H
H
H
transannularhydrideshi`s
HO Me
HO D HO D
Me Me D
O
H- H2O
- H
Me H
HO Me
SbF5, FSO3F
-140 °C
Me
Me
H
δH=-0.51ppm
BHB
H
H
H
H
H
δH=-3.9ppm
cyclodecylcaZon–3-centre-2-electronbondc.f.diborane 1
3
56
H
H
H
δC=142ppm
δH=-6.85ppm
δH=+6.80ppm
δC=153ppm
δH=+4.0ppm
1,6-caZonslightlyhigherinenergythan1,5-caZon
Page 29
Rearrangements and Reactive Intermediates
29
Me MeMe Me
Ph CO2H
CO2
PhPh
CO2
Ph
PhHO2C
Carbanionrearrangements– carbanionsaremuchlesspronetorearrangementthancarbocaZons
ClPhPh
LiPhPh
2Li, -60 °C
-LiCl
CO2
CO2HPhPh
Ph
Ph
delocalisedthereforemorestablecarbanion
1,2-arylshi`s
evidenceforspirocyclicintermediate
Cl
MeMe
Me Me
Ph
Li, -75 °C
then CO2
CO2H
MeMe
Me Me
Ph
Cs-K-Na alloy
-75 °C
Me Me
Ph
Me
Me
Ph
Me MeMe Me
0 °C
X-raystructure
delocalised,dearomaZsedcarbanionmorestablethan3°carbanion
3°carbanion
Page 30
Rearrangements and Reactive Intermediates
30
overallintheFavorskiirearrangementanalkylgroup(R)movesfromonesideofthecarbonylgrouptotheother
OMeO
MeOH
OCl
FavorskiirearrangementO
Cl NaOMe
OMeO
NaOMe
O O O
O OMeOMeO
MeOH
OMe
O
oxyallylcaZon
2-electronelectrocyclicringclosure-moreofthisnextyear
SE1
symmetricalintermediateestablishedbyLo}ieldwithdoublylabelledsubstrate=14Clabel
OCl
O
NaOMe
O O OMeMeO
OMeO
MeOH 1:1mixture
O
RR'
X
OR'
R
R''OR''O
Page 31
Rearrangements and Reactive Intermediates
31
quasi-Favorskiirearrangement– Favorskiirearrangementonsubstrateswithnoenolisablehydrogenatoms
Ramberg-BäcklundreacZon
MeNPh
OCl
HO
MeN
O
OHPh
MeNPh
Cl OHO
themechanismisabasecatalysedsemi-pinacolrearrangementandiscloselyrelatedtothemechanismofthebenzil-benzillicacidrearrangement
SO O
Cl NaOMe SO O
Cl SO O
OSO
cheletropicextrusionofSO2–morenextyear
concerted1,2-shi`sofcarbanionsaregeometricallyimpossible-asthecarbanioncannotreachtoperformanintramolecularSN2reacZonwithinversionofconfiguraZon
R
RR
R
R'''
R''R'
Page 32
Rearrangements and Reactive Intermediates
32
PhN
O Me
Me•••
•
PhN
O Me
Me
O
Me•
•
Concerted1,2-shi`sofcarbanionsaregeometricallyimpossible-asthecarbanioncannotreachtoperformanintramolecularSN2reacZonwithinversionofconfiguraZon
R
RR
R
R'''
R''R'X
1,2-Shi`sofcarbanionsoccurbyaradicalmechanism–1,2-Wicg,1,2-Stevensandrelatedrearrangements.
1,2-Wicgrearrangement
OMe
OMe
BuLi
O
Me
OMe•
• OH
Mesolventcage
Stevensrearrangement
PhN
OMe MeHO
PhN
OMe Me
PhN
O Me
Me•
•
solventcage
