Rearrangements and Reactive Intermediates 1

Rearrangements and Reactive Intermediates

Hilary Term 2018 1A Organic Chemistry

Handout 1

http://burton.chem.ox.ac.uk/teaching.html◼ PolarRearrangements,OxfordChemistryPrimerno.5;L.M.Harwood◼ OrganicChemistry J.Clayden,N.Greeves,S.Warren– Chapters36-41◼ ReactiveIntermediates,OxfordChemistryPrimerno.8;C.J.Moody,G.H.Whitham

◼MechanismandTheoryinOrganicChemistry,T.H.Lowry,K.S.Richardson◼ AdvancedOrganicChemistry,F.A.Carey,R.A.Sundberg◼ModernPhysicalOrganicChemistry;E.Anslyn,D.Docherty

Me Me

MeHO

H Me

Me

1

23

4567

8

12

4 56

7

8

3

isoborneol

jonathan.burton@chem.ox.ac.uk

camphene

Rearrangements and Reactive Intermediates 2

◼ Carbocationsandcarbanions NMRspectroscopyandX-raystructuresofcarbocations;aggregationandpyramidalinversionofcarbanions.Reactivity,includingSE1,redox,hydrideeliminationandrearrangements:Wagner–Meerwein,pinacol,semi-pinacol.

◼ Rearrangementofanionsandcarbocations Orbitaltheory;Is3c-2estructureTSorHEI?Stepwiseversus concertedrearrangements;non-classicalcarbocations (carbonium ions),transannular hydrideshifts.Carbanions:Favorskii,Ramberg-Bäcklund,StevensandWittigrearrangements.

◼ Carbenes Structuralfeaturesthatinfluencestability.Methodsofmakingthem;carbenesversuscarbenoids.Generalclassificationofthetypesofreactionthatthesespeciesundergo.Rearrangements:Wolff,cyclopropanation,C-Hinsertion.

◼ Rearrangementstoelectron-deficientnitrogenandoxygen Structureofnitrenes;structuralfeaturesthatinfluencestability.Methodsofmakingthem.Typesofreaction:aziridination,C–Hinsertion.Nitrene versus non-nitrenemechanisms.Rearrangementstoelectron-deficientnitrogen(Beckmann,Neber,Hoffmann,Curtius,Schmidt,Lossen).Baeyer–Villiger rearrangement.

◼ Introductiontoradicals Structure;stability.Generaltypesofreactioninvolvingradicals:homolysis,recombination,redox,addition,β-scission,substitution,disproportionation.

◼ Problemclassrelatingtolectures1–4.

◼ Casestudies Elucidatingmechanismsofrearrangements.EvidenceforcurrentlyacceptedmechanismsfortheBaeyer–Villiger,BeckmannandFavorskii rearrangements.

◼ Problemclassrelatingtolectures5and7.

Synopsis

Rearrangements and Reactive Intermediates 3

R

R

RR

R••

RRR

◼ ElectronDeficientCationsTwoclassesofcarbocations

Carbeniumion(6electrons)

Carbonium ion(8electrons)

Radicalcation

CH5

◼ ElectronRichAnionsCarbanion(8electrons)

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)

reactivetowardsa) nucleophilesb) basesc) reducingagents

e.g.

reactivetowardsa) electrophilesb) acidsc) oxidisingagents

reactivetowardsa) electrophilesornucleophilesb) otherhighenergyagentsc) oxidisingorreducingagents

◼ Neutralspeciesketenes

• OR

R

◼ Neutralspeciesarynes

RR

R

R

RR

R ••R

R ••

R

R

Rearrangements and Reactive Intermediates 4

Me

Me

Me

1.44Å

1.62Å

1.52Å

118°99°

111°

◼ Bondlengthsandbondanglesprovideevidenceofhyperconjugation (T.Laube,Angew.Chem.Int.Ed.1986,25,349).

◼ Crystalstructureofanadamantyl carbocation

F5SbFSbF5

1.53Å

110°

adamantane

Me

Me

Me Me

Me

MeMe

Me

Me

Me

Me

Me

Me

MeMe

F

2SbF5

SO2

δC 294ppmδC 71ppm

δC 90ppm

δC 30ppm

δC 49ppm

C-C sp3-sp3 1.54 Å

C-C sp3-sp2 1.50 Å

C-C sp2-sp2 1.46 Å

C=C 1.34 Å

δC 38ppm

δC 29ppm

Stuctures ofCarbocations

◼ C-C σ to empty p

Rearrangements and Reactive Intermediates 5

◼ Crystalstructureofat-butylcarbocation

F5SbFSbF5

C-C sp3-sp3 1.54 Å

C-C sp3-sp2 1.50 Å

C-C sp2-sp2 1.46 Å

C=C 1.34 Å

H HH

H

HH

H

HH

1.44Å

120°

◼ Bondlengthsprovideevidenceofhyperconjugation (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(adamantyl acidfluoride)

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-bondsthegreatertheextentofhyperconjugation andthegreaterstabilisation

CH3

CH3

H

HH

donationofC-Hσ-bond(orC-Cσ-bond)electronsintoemptyporbital

◼ carbeniumionstabilitythereforegoesintheorder:

◼ conjugationwithalkenes,arenesandlonepairs,alsostabilises carbeniumions

◼mostcarbocations arefleetingreactionintermediates– thetriphenylmethyl (trityl)cation persists-crystalstructureoftrityl cation demonstratesallthephenylgroupsaretwistedoutofplane

B(CN)4

OHPh

PhPh

H2SO4

CH2Cl2

HSO4

◼ Hyperconjugation

δC =212ppm

◼ Ph3CBF4 isacommerciallyavailablecrystallinesolid

Rearrangements and Reactive Intermediates 7

◼ generallyaggregatedinthesolidstateandinsolution

StructuresofCarbanions

◼ methyllithium isatetramer(MeLi)4 withCH3 groupssittingaboveeachfaceofaLi4 tetrahedron— overalladistortedcube

◼ tert-butyllitium isalsotetrameric inthesolidstate(X-raycrystalstructuresbelow)

Li

C

C

Li

C

Li

Li

C

methyllithium(MeLi)4

(H-atomsremovedforclarity)

t-butyllithium(t-BuLi)4

◼ incoordinatingsolventse.g.THF,Et2Omostorganolithiums becomelessaggregatedandhencemorereactive

idealisedarrangementoflithiumandcarbonatoms

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

◼ stabilityofcarbanions isrelatedtothepKaoftheirconjugateacids

increasingpKaofconjugateacid,increasingreactivity,decreasingstability

16 24 41 43 44

46 48 50 51 53

aromatic sp-hybridised conjugated sp2-hybridised sp2-hybridised

sp2-hybridised sp3-hybridisedsp3-hybridisedelectrondonatingalkylgroup

sp3-hybridisedelectrondonatingalkylgroups

sp3-hybridisedelectrondonatingalkylgroups

increasingpKaofconjugateacid,increasingreactivity,decreasingstability

Rearrangements and Reactive Intermediates 9

PhBr

PhLi

RBr

Ph RtBu Li

◼ sp2 hybridisationattransitionstateforpyramidalinversion◼ ideal120° anglesonlyca.60° forcyclopropane◼ transitionstatehighlystrainedthereforeslowrateofinversion

◼ pyramidalinversionisgenerallyfastforsp3hybridisedcarbanions (theyareisoelectronicwithNH3)andhencechiralcarbanions generallyundergorapidracemisation.

R

‡

◼ vinylanionsandcyclopropylanionsaretheexceptionsandaregenerallyconsideredconfigurationallystable

◼ 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

Rearrangements and Reactive Intermediates 10

RH

- H

ReactionsofCarbocationsandCarbanions

◼ Genericreactionmapofcarbocations andcarbanions

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

carbocationrearrangement

hydrideloss

ionisation

deprotonation

reactionwithnucleophile

singleelectrontransfer(SET)

SET

electrophilereaction

reductiondeprotonation

carbanionaddition

hydrideloss

reactionwithelectrophile

electrophilicsubstitution

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 +

◼ mostcommonreactionofcarbanions isreactionwithelectrophiles(e.g.RLi orRMgBr plusE⊕)whichisamplycoveredelsewhere

◼ someotherreactionsareshownbelow

SE1– Subsitution ElectrophilicUnimolecular - formallyrelatedtoacarbanionasSN1istoacarbocation

◼ genericmechanism

RRX - X

SE1

ER

E

◼ examples

OPPhPh

HO

Ph

OH

Ph

OOH O

Ph Ph

OBr

Br Br

Rearrangements and Reactive Intermediates 12

◼ β-hydrideeliminationfromcarbanions commonfortransitionmetals

PdXH

+ HPdX

◼ reversereactionishydrometallation – wellknownfromhydroborationchemistry

HBR2 BR2

H

◼ notacommonreactionforGrignardreagentsororganolithiums;however,β-hydrideeliminationisadecompositionpathwayfororganolithiums andtert-butyllithium canactasasourceofhydride

HLi

MeMe

Me

Me+ LiH

◼ redoxreactions– SingleElectronTransfer- SET

MgBr+

ClCl •

H

H

HH+

SET

• ClCl•+

dimerisationof Ph•

Cl

•

SETCl

Rearrangements and Reactive Intermediates 13

MeLG

HHNu Nu

R'R'' LG

H H

LGNu(-) (-)

‡Me

Me Me MeMe

MeMeMe

◼ rearrangementofcarbocations

Me

MeMe

I

AgNO3, water

Me

Me MeHO

Me

Me Menot

Me

MeMe

OH+

Ag

Me

MeMe

◼ theneopentyl system

◼ asanaside,rememberthatneopentyl systems,althoughprimary,areunreactiveunderSN2conditionsasthenucleophileisseverelyhinderedfromattackingthenecessarycarbonatom

Me

Me Me1,2- shift

H2Othen - H - H

◼ the1,2shiftisaWagner-Meerwein rearrangement

◼ staggeredconformationrequiresnucleophiletoapproachpassedoneofthemethylgroups

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-Meerwein rearrangementsexemplifiedMe 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

◼ secondarycarbocation

◼ tertiarycarbocation

1

23

456

7

8

MeMe

Me

◼ orbitaloverlapσC-Cintoemptyp-orbital

Me Me

Me

1

23

4567

8

◼ ingeneralalkylshiftsoccurtoyieldamorestablecarbocation

bestorbitaloverlapformigration(ca.co-planar)

poororbitaloverlapformigrationmigration

wouldleadto4-memberedring

isoborneol camphene

Rearrangements and Reactive Intermediates 15

Me

Me

12

4 56

7

8

3

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

◼Wagner-Meerwein rearrangementsexemplified– Naturewasherebeforeus– biosynthesisofcamphene

Me 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° cation ◼ form3° cation ◼ form2° cationreliefofringstrain

◼Wagner-Meerwein rearrangementsexemplified– Naturewasherebeforeus– biosynthesisoflanosterol(precursorof cholesterol)

HO

Me

Me

Me

Me

Me

H

MeH

H H

Me Me

squalene oxide lanosteroltwo1,2-hydrideshiftstwo1,2-methylshifts

chair– boat– chairconformation

◼ conformationofsqualeneoxidecontrolledbyenzyme(lanosterolsynthase)– reactionoccursviadiscretecarbocationintermediatesandisnotconcerted

H

linalylpyrophosphate

- H

camphene

Rearrangements and Reactive Intermediates 16

◼mechanisminmoredetailcorrectorbitaloverlaprequiredformigration

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

nO toσ*C-C

σC-C toemptyp

◼ usefulmethodforthepreparationofspirocyclicketones.

OH

HO H

OH

H2O

OH OOH

-H

pinacol pinacolone

◼ thestartingdiolscanbereadilypreparedbythepinacolreaction

O Mg

SET

O

•Mg2

O OMg

• •

OMg

O

◼ epoxidesandhalohydrins canbesubstratesforthepinacolrearrangement

Rearrangements and Reactive Intermediates 17

O i) CNii) LiAlH4

or

i) CH3NO2. EtOii) LiAlH4

HNO2HO

N2 OH O

- HHO

NH2

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-Demayanov reaction

◼ semi-pinacolrearrangements- stereochemistry

◼ anti-periplanar bondsmeansbestoverlapofσ andσ*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-C toσ*C-N

σC-C toσ*C-N

σC-H toσ*C-N

nO toσ*C-N

tBuO

H

tBuO

H

tBu

O

tBuO

nO toσ*C-C

nO toσ*C-C

nO toσ*C-H

Rearrangements and Reactive Intermediates 18

OH

Me Me

O

Me Me

◼ thedienone-phenolrearrangement– formallythereverseofthepinacolrearrangement

OH

Me Me

H

OH

Me

MeH

OH

MeMe

◼ thepinacolrearrangementisdrivenbyformationofastrongC=Obond

◼ thedienone-phenolrearrangementinvolveslossofaC=Obondandgainofanaromaticring

◼ thedienone-phenolrearrangementcanbemechanisticallycomplexbutcanalsojustinvolveasimple1,2-shiftofanalkylgroup

Cl

OHtBuO

Cl

O O

H

OH

◼ thedienone-phenolrearrangementprovidesamethodforringannulation

Rearrangements and Reactive Intermediates 19

R

RR

R

R

R

R

R

R

RR

R

R'''

R''R'

R''' R''R' R'''

R''

R'

Theoryof1,2-shifts◼ curlyarrowmechanism

◼ orbitaldescription

◼ 3-centre-2-electronsystematthetransitionstate

◼ inthetransitionstatewehavethreeorbitalsandtwoelectronstodistributec.f.theallylcation

•

ψ1

ψ2

ψ3

allylcation 1,2-shifttransitionstate(carbocation)

R

R

R

R

R

R

R

R

R

R

R

R

ψ1

ψ2

ψ3

R

R

C

R

R

R

R

R

R

R

R

C

R

R

C

R

R

R

R

R

R

R

R

R

R

R

R

ψ1

ψ2

ψ3

1,2-shifttransitionstate(carbanion)

retention retention

Rearrangements and Reactive Intermediates 20

R

RR

R

R'''

R''R'

◼ 1,2-cationand1,2-anionshifts◼ overallforcarbocation1,2-shift,transitionstatehasnetbonding

◼ thetransitionstatehas2electronscyclicallyconjugatedinaringandisthereforearomatic– moreofthisnextyear

◼ bothy2 andy3 areantibonding

◼ therefore1,2-shiftsofcarbanions andradicalswouldbeexpectedtobefarlessfavourable(y2 isoccupied)

◼ transitionstatefor1,2-shiftofcarbanions has4electronscyclicallyconjugated(y1

2y22)inaringandisanti-aromatic

◼ takehomemessage – 1,2-shiftseasyforcarbocations,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-shifttransitionstatecarbanion

1,2-shifttransitionstatecarbocation

◼ 1,2-shiftsoccurwithretentionofconfigurationinthemigratinggroup

◼ the3-centre-2-electronstructuremaybeatransitionstateorahighenergyintermediate◼ aswehaveseen,concertedmigrationwithlossoftheleavinggroupisanothermechanisticpossibility

◼ onecanalsoviewthedifficultyof1,2-carbanionshiftsarisingfromthegeometricalimpossibilityofthecarbanionperforminganintramolecularSN2reactionwithinversionofconfiguration

X

Rearrangements and Reactive Intermediates 21

HH H

H

H

◼ aswehaveseen,forefficientrearrangementorbitalalignmentiscritical

◼ retentionofconfigurationatthemigratingcentreisobserved

◼ allthreeindicatedhydrogenatomsareinthesameplane-rearrangementtothemorestable3° carbocationdoesnotoccur

Me

Me MeNH2

Me

HNO2Me

Me MeN2

Me

Me

Me

MeMe

Me

Me

MeMe

HOH2O

◼ migrationwith98%retentionofconfiguration

◼ atthemigratingterminusinversionorracemisationcanoccur

MeEtHO OH H

MeEtH2O OH Et

Me H

OH Et

Me H

OH

enantiopure racemic

◼ racemisationwilloccurifthemechanismisSN1-likei.e.viaafullcarbocation

◼ inversionatthemigratingterminuswilloccurifthemechanismisconcerted

Rearrangements and Reactive Intermediates 22

Br

Br HMe

Me HMeH

Br

HMe

MeH

Br

MeH

Br

Br MeH

Me H

HBr

ConcertedRearrangements

◼ Neighbouringgroupparticipation(NGP)

Definition(IUPAC):thedirectinteractionofthereactioncentre (usually,butnotnecessarily,anincipientcarbeniumcentre)withelectronscontainedwithintheparentmoleculebutnotconjugated withthereactioncentre – couldbelonepair,π-bond,orσ-bond

Br

OHMeH

HMe HBr

Br

OH2MeH

MeH

Br

Br

OH2MeH

HMe

Br

diastereomericsingleenantiomerbromohydrins

meso

C2 symmetric

◼ enantiomerssamerelativeconfigurationasstartingmaterialracemicproduct

◼ samestructuremeso - achiral

◼ outcomeofabovereactionsisexcellentevidenceforsymmetricalintermediatesandhenceneighbouringgroupparticipation

Arateincreaseduetoneighbouringgroupparticipationisknownas'anchimeric assistance’neighbouringgroupparticipationandanchimeric assistanceareoftenusedinterchangeably

Br

OHMeH

MeH

Br

BrMeH

MeH

Br

BrMeH

HMe

inversioninversion

inversioninversion

Rearrangements and Reactive Intermediates 23

◼ alternativeperspectiveofNGP

TsO

H

7

12

3

45

6

◼ whydothesesingleenantiomertosylates undergosolvolysis atsignificantlydifferentratestogivethesameracemicproduct?◼ non-classicalcarbocations,A.K.A.carbonium ions

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-electronbond

O

Me OH

rdsnoNGP

◼ exo-Ts reactsfasterduetoNGPofantiperiplanar C-Csigmabond◼ endo-Ts ionisesslowertogiveclassicalcarbocationfollowedbynon-classicalcarbocationformation◼ non-classicalcation hasplaneofsymmetryleadingtoracemicproducts

exo-Tsendo-Ts

◼ non-classicalcarbocation-carbonium ion

racemic

rotate

Rearrangements and Reactive Intermediates 24

MeMe

Me Me

◼ evidencefornon-classicalcarbocation(carbonium ion)overequilibratingcarbeniumionsforthe2-norbornylcationi.e.isthenon-classicalcation anintermediateorTS?

◼ lowtemperature13CNMR(5K)showsasymmetricalion

◼ X-raycrystalstructure(Science,2013,341,62)provideddefinitiveevidenceofbridgedstructure

1.8Å

δC 125ppm

◼ Note: non-classicalcarbocations areonlyformediftheyaremore stablethantheirclassicalcounterpartsBr3AlBrAlBr3

◼ The1,2-dimethylnorbornylcation isarapidlyequilibratingspecieswithpartialσ-delocalisation.

Me Me

Me

Me

1.7Å2.1Å

F5SbFSbF5

◼ X-raystructureoftheanalogoustetramethylnorbornyl cation alsodemonstratespartialσ-delocalisation.

Rearrangements and Reactive Intermediates 25

AcOH

AcOH

AcOH

J

H

H

OAc

AcOH

OTsAcOH

◼ π-bondsarebetterdonorsthanσ-bonds

TsO

OMe

HOAcO OAc

TsOO

Me

HO AcO

OTs

H

HHH

krel =1

krel =1011

krel =104

krel =107

SbF6 SbF6

Ph

Me

Me

classicalcarbocation(carbeniumion)

non-classicalcarbocation(carbonium ion)

allylcation

J.Am.Chem.Soc.,1989,111,9224

◼ completeretentionofconfiguration(doubleinversion)

◼ samestructure

H

Rearrangements and Reactive Intermediates 26

AcO MeH

H Me

AcO HMe

H MeOTsH

Me

HMe

◼Moreneighbouringgroupparticipationwithπ-bonds– phenonium ions

HMe

HMe

O

Me OH

OTsHMe

MeHAcOH

HMe

MeH

O

Me OH

◼ enantiomersracemicproduct

diastereomericsingleenantiomer

substrates

◼meso phenonium ion(σ-plane)

◼ C2-symmetricphenonium ion

◼ samesingleenantiomerproduct

69ppm

δC =60ppm

172ppm

133ppm155ppm

AcOH

inversion

inversion

inversion

inversion

OAcHMe

HMe

OAcHMe

MeH

Rearrangements and Reactive Intermediates 27

H2, Pd

MeMe

Br AlBr3

heat

H2O

- H

◼multiple1,2-shifts

OHMe

H

MeHO

Me

- H2OH

Me Me Me

MeMe

◼ formationofadamantane

Diels-Alder

C10H16 adamantaneC10H16

◼ allC10H16 hydrocarbonsrearrangetoadamantaneontreatmentwithLewisacid

◼ adamantaneisthethermodynamicallymoststableC10H16 isomer– itpossessrepeatingunitsofthediamondlattice

MeMe

H

Rearrangements and Reactive Intermediates 28

H

H

H

H

H

H

H

H

H

Cl

SbF5, FSO3F

-140 °Cor or H

H

H

◼ transannular hydrideshifts

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

◼ cyclodecyl cation – 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-cationslightlyhigherinenergythan1,5-cation

Rearrangements and Reactive Intermediates 29

Me MeMe Me

Ph CO2H

CO2

PhPh

CO2

Ph

PhHO2C

◼ Carbanionrearrangements– carbanions aremuchlesspronetorearrangementthancarbocations

ClPhPh

LiPhPh

2Li, -60 °C

-LiCl

CO2

CO2HPhPh

Ph

Ph

◼ delocalisedthereforemorestablecarbanion

◼ 1,2-arylshifts

◼ 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,dearomatised carbanionmorestablethan3° carbanion

◼ 3° carbanion

Rearrangements and Reactive Intermediates 30

O

◼ overallintheFavorskiirearrangementanalkylgroup(R)movesfromonesideofthecarbonylgrouptotheother

OMeO

MeOH

OCl

◼ Favorskii rearrangementO

Cl NaOMe

OMeO

NaOMe

O O

O OMeOMeO

MeOH

OMe

O

oxyallyl cation

◼ 2-electronelectrocyclicringclosure- moreofthisnextyear

SE1

◼ symmetricalintermediateestablishedbyLoftfield withdoublylabelledsubstrate=14Clabel

OCl

O

NaOMe

O O OMeMeO

OMeO

MeOH ◼ 1:1mixture

O

RR'

X

OR'

R

R''OR''O

Rearrangements and Reactive Intermediates 31

R

RR

R

R'''

R''R'

◼ quasi-Favorskii rearrangement– Favorskii rearrangementonsubstrateswithnoenolisable hydrogenatoms

◼ Ramberg-Bäcklund reaction

MeNPh

OCl

HO

MeN

O

OHPh

MeNPh

Cl OHO

◼ themechanismisabasecatalysedsemi-pinacolrearrangementandiscloselyrelatedtothemechanismofthebenzil-benzillic acidrearrangement

SO O

Cl NaOMe SO O

Cl SO O

OSO

◼ cheletropic extrusionofSO2

– morenextyear

◼ concerted1,2-shiftsofcarbanionsaregeometricallyimpossible- asthecarbanioncannotreachtoperformanintramolecularSN2reactionwithinversionofconfiguration

Rearrangements and Reactive Intermediates 32

PhN

O Me

Me•••

•

PhN

OMe MeHO

PhN

OMe Me

O

Me•

•

PhN

O Me

Me

◼ Concerted1,2-shiftsofcarbanionsaregeometricallyimpossible- asthecarbanioncannotreachtoperformanintramolecularSN2reactionwithinversionofconfiguration

R

RR

R

R'''

R''R'X

◼ 1,2-Shiftsofcarbanionsoccurbyaradicalmechanism– 1,2-Wittig,1,2-Stevensandrelatedrearrangements

◼ 1,2-Wittigrearrangement

OMe

OMe

BuLi

O

Me

OMe•

• OH

Mesolventcage

◼ Stevensrearrangement

PhN

O Me

Me•

•

solventcage

Rearrangements and Reactive Intermediates 33

O

MeH

•

•O

Me H

O

Me HH

BuLi

◼ the1,2-Wittigrearrangementoccurspredominantlywithretentionofconfigurationinthemigratinggroup

solventcage

O•

MeH

•

O

HMe

OH

HMe

H

◼ predominantretentionofconfigurationatthemigratingcentre*

* *