Rearrangements and Reactive Intermediates jonathan.burton@chem.ox.ac.

uk 1

Rearrangements and Reactive

Intermediates
Hilary Tem 2017
1A Organic Chemistry

Handout 1
Me 1 Me
7
2
2
7
3 H 3 1 Me
HO 6
5 4
Me 4 6 5 Me
8
8
isoborneol camphene

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

︎ ︎Polar Rearrangements, Oxford Chemistry Primer no. 5; L. M. Harwood

︎ Organic Chemistry J. Clayden, N. Greeves, S. Warren – Chapters 36-41
Reac4ve Intermediates, Oxford Chemistry Primer no. 8; C. J. Moody, G. H. Whitham

Mechanism and Theory in Organic Chemistry, T. H. Lowry, K. S. Richardson
Advanced Organic Chemistry, F. A. Carey, R. A. Sundberg
Modern Physical Organic Chemistry; E. Anslyn, D. Docherty

Rearrangements and Reactive Intermediates 2

Synopsis

Carboca'ons and carbanions NMR spectroscopy and X-ray structures of carbocaZons; aggregaZon and pyramidal
inversion of carbanions. ReacZvity, including SE1, redox, hydride eliminaZon and rearrangements: Wagner–Meerwein,
pinacol, semi-pinacol.

Rearrangement of anions and carboca'ons Orbital theory; Is 3c-2e structure TS or HEI? Stepwise versus concerted
rearrangements; non-classical carbocaZons (carbonium ions), transannular hydride shi`s.
Carbanions: Favorskii, Ramberg-Bäcklund, Stevens and Wicg rearrangements.

Carbenes Structural features that influence stability. Methods of making them; carbenes versus carbenoids. General
classificaZon of the types of reacZon that these species undergo. Rearrangements: Wolff, cyclopropanaZon, C-H
inserZon.

Rearrangements to electron-deficient nitrogen and oxygen Structure of nitrenes; structural features that influence
stability. Methods of making them. Types of reacZon: aziridinaZon, C–H inserZon. Nitrene versus non-nitrene
mechanisms. Rearrangements to electron-deficient nitrogen (Beckmann, Neber, Hoffmann, CurZus, Schmidt, Lossen).
Baeyer–Villiger rearrangement.

Introduc'on to radicals Structure; stability. General types of reacZon involving radicals: homolysis, recombinaZon,
redox, addiZon, β-scission, subsZtuZon, disproporZonaZon.

Problem class relaZng to lectures 1–4.

Case studies ElucidaZng mechanisms of rearrangements. Evidence for currently accepted mechanisms for the Baeyer–
Villiger, Beckmann and Favorskii rearrangements.

Problem class relaZng to lectures 5 and 7.

Rearrangements and Reactive Intermediates 3

Types of High Energy Intermediates Electron Rich Anions reac4ve towards

Carbanion (8 electrons) a)  electrophiles
Electron Deficient CaZons reac4ve towards
b)  acids
Two classes of carbocaZons a)  nucleophiles
R R c)  oxidising agents
b)  bases
••
Carbenium ion (6 electrons) c)  reducing agents R R
R R
R R R R
R R Electron Rich Anions
Radical Anion
Carbonium ion (8 electrons) H H
e.g. H H H H
CH5 •

Radical caZon H H H H
H H
H H
H H H H Neutral species
•
•+ Radical (7 electrons)
H H H H
reac4ve towards
H H R a)  electrophiles or nucleophiles
R • b)  other high energy agents
Neutral species R c)  oxidising or reducing agents
Carbenes (6 electrons)

R • R Neutral species Neutral species

R R •• R ketenes Arynes
•
R R R R R R
• O
singlet triplet R
Rearrangements and Reactive Intermediates 4

Stuctures of Carboca'ons
Crystal structure of an adamantyl carbocaZon
110°
1.44 Å
118°
99°
1.53 Å

1.62 Å 111° δC 38 ppm

Me Me δC 29 ppm

1.52 Å F 5SbFSbF5 adamantane

Me

Me Me Me Me Me Me

Me Me Me
δC 294 ppm
F
C-C sp3-sp3 1.54 Å δC 71 ppm

C-C sp3-sp2 1.50 Å 2SbF5 δC 90 ppm

C-C sp2-sp2 1.46 Å Me Me SO2 Me Me δC 30 ppm
C=C 1.34 Å Me Me δC 49 ppm

Bond lengths and bond angles provide evidence of hyperconjugaZon (T. Laube, Angew. Chem. Int. Ed. 1986, 25, 349).
Rearrangements and Reactive Intermediates 5

Crystal structure of a t-butyl carbocaZon

H
H H
C-C sp3-sp3 1.54 Å 1.44 Å
C-C sp3-sp2 1.50 Å
H H
C-C sp2-sp2 1.46 Å
C=C 1.34 Å H H
H H
F 5SbFSbF5
120°

δC = 335 ppm
O
F CH3
2SbF5 2SbF5
δC = 94 ppm H 3C
F
H 3C CH3 SO2 H 3C CH3 SO2 H 3C
CH3 CH3 δC = 171 ppm
δC = 28 ppm
δC = 47 ppm δH = 4.35 ppm (adamantyl acid fluoride)

δC = 320 ppm
F H δH = 13.5 ppm
SbF5

H 3C CH3 SO2 H 3C CH3

δH = 5 ppm
δC = 51.5 ppm
Bond lengths provide evidence of hyperconjugaZon (T. Laube, J. Am. Chem. Soc. 1993, 115, 7240).
Rearrangements and Reactive Intermediates 6

HyperconjugaZon
donaZon of C-H σ-bond (or C-C σ-
bond) electrons into empty p orbital empty
p-orbital

H filled σ C-H
CH3 orbital
H
CH3
H energy of the bonding electrons reduced
system stabilised
greater number of C-H (or C-C) σ-bonds the greater the extent of hyperconjugaZon and the greater stabilisaZon
tertiary secondary primary
carbenium ion stability therefore goes in the order:
R R > R R > R

R
conjugaZon with alkenes, arenes and lone pairs, also stabilises carbenium ions
most carbocaZons are fleeZng reacZon intermediates – the triphenylmethyl (trityl) caZon persists -
crystal structure of trityl caZon demonstrates all the phenyl groups are twisted out of plane
Ph3C BF4 is a commercially available crystalline solid

HSO 4
Ph H 2SO 4
Ph OH
Ph CH 2Cl 2

δC = 212 ppm
B(CN)4
Rearrangements and Reactive Intermediates 7

Structures of Carbanions

generally aggregated in the solid state and in soluZon

methyllithium is a tetramer (MeLi)4 with CH3 groups sicng above each face of a Li4 tetrahedron
— overall a distorted cube

tert-butylliZum is also tetrameric in the solid state (X-ray crystal structures below)

Li
C
C
Li
C
Li
Li
C

t-butyllithium methyllithium idealised arrangement of

(t-BuLi)4 (MeLi)4 lithium and carbon atoms
(H-atoms removed
for clarity)
in coordinaZng solvents e.g. THF, Et2O most organolithiums become less aggregated and hence more reacZve
 Rearrangements and Reactive Intermediates 8

stability of carbanions is related to the pKa of their conjugate acids

H
H
H H H
H

increasing pKa of
conjugate acid, 16 24 41 43 44
increasing reacZvity,
decreasing stability
H H
H H
H H

aromaZc sp-hybridised conjugated sp2-hybridised sp2-hybridised

CH3 CH3CH 2 (CH 3) 2CH (CH 3) 3C

increasing pKa of H
conjugate acid, 46 48 50 51 53
increasing reacZvity,
decreasing stability

H H H H Me H Me Me
H H Me Me Me

sp3-hybridised sp3-hybridised sp3-hybridised

sp2-hybridised sp3-hybridised electron donaZng electron donaZng electron donaZng
alkyl group alkyl groups alkyl groups
Rearrangements and Reactive Intermediates 9

pyramidal inversion is generally fast for sp3 hybridised carbanions (they are isoelectronic with NH3) and hence
chiral carbanions generally undergo rapid racemisaZon.
‡
fast
R'' R R''
R'' R R'
R' R R'

vinyl anions and cyclopropyl anions are the excepZons and are generally considered configuraZonally stable

lithium halogen exchange with alkenyl iodides and bromides is a stereospecific process

tBu Li Br
Ph Ph R
Br Li Ph R

tBuLi Br
R
Br Li R
Ph Ph Ph

Br Li CO 2H sp2 hybridisaZon at transiZon state for

Me BuLi Me CO 2 Me pyramidal inversion
ideal 120 ° angles only ca. 60° for cyclopropane
Ph Ph Ph Ph Ph Ph
transiZon state highly strained ‡
(S) retention therefore slow rate of inversion
R
Rearrangements and Reactive Intermediates 10

Reac'ons of Carboca'ons and Carbanions

Generic reacZon map of carbocaZons and carbanions

hydride loss reacZon with

nucleophile reducZon
carbocaZon deprotonaZon
E
Nu rearrangement X
R R
H R H
R R
+ 2e electrophilic
-H Nu -H
ionisaZon SET subsZtuZon

X -X +e +e -X X
R R R R R
SN1 or E1 • SE1
-e -e
single electron
-H transfer (SET) E -H
R
E R
R
R reacZon with R
electrophile electrophile carbanion
deprotonaZon hydride loss
reacZon addiZon
Rearrangements and Reactive Intermediates 11

⊕
most common reacZon of carbanions is reacZon with electrophiles (e.g. RLi or RMgBr plus E ) which is amply
covered elsewhere

some other reacZons are shown below

SE1 – SubsituZon Electrophilic Unimolecular - formally related to a carbanion as SN1 is to a carbocaZon

generic mechanism

X -X E E
R R R
SE1

examples

O OH O O O
Br Br
H Br
Ph Ph Ph Ph

R - N2 R ROH R
N H
R N R R

O O O O
HO
P OH, H 2O Ph P P P H
Ph HO Ph + O Ph +
Ph Ph Ph Ph
heat
Rearrangements and Reactive Intermediates 12

β-hydride eliminaZon from carbanions common for transiZon metals

reverse reacZon is hydrometallaZon – well known from hydroboraZon chemistry

H
H H
PdX + HPdX BR 2
BR 2

not a common reacZon for Grignard reagents or organolithiums; however, β-hydride eliminaZon is a decomposiZon
pathway for organolithiums and tert-butyllithium can act as a source of hydride

Li Me
Me H + LiH
Me
Me
redox reacZons – Single Electron Transfer - SET

MgBr Cl H
+ Cl + H •
H H
dimerisation
SET of Ph•

Cl Cl
• Cl SET
+ Cl
•
•
Rearrangements and Reactive Intermediates 13

rearrangement of carbocaZons
the neopentyl system
Me AgNO3, water Me Me Me Me Me
Me HO + not Me
Me I Me Me Me OH
Ag
H 2O
then - H -H

Me 1,2- shift Me Me the 1,2 shi` is a Wagner-

Me Meerwein rearrangement
Me Me

as an aside, remember that neopentyl systems, although primary, are unreacZve under SN2 condiZons as the
nucleophile is severely hindered from a"acking the necessary carbon atom

Me ‡
Me Me
Me Me Me
Me
Me (-) (-) Me
LG Nu LG Nu R'' LG
Nu H
H R'
H H

staggered conformaZon
requires nucleophile to
approach passed one of the
methyl groups
Rearrangements and Reactive Intermediates 14

Wagner-Meerwein rearrangements exemplified

Me 1 Me
7 7
2
7
3 H 3
2 1 Me -H 3
2
1 Me
HO 6
5 overall red bond is broken and
4
Me 4 6 5 Me Me
8
4 6 5
blue bond is formed
isoborneol camphene 8 Me
8

H
in general alkyl shi`s occur
rotate
to yield a more stable
Me 1 Me Me 1 Me Me 1 Me Me carbocaZon
1 Me
2 2 Me
7 2 7 8
3 7 3 2 5
H 2O 6 6
3 6 5
6 best orbital overlap is also
5 4 5 4 rotate 7
Me Me
4
8 Me 3 important in determining
8 8 4
which group migrates
secondary terZary
carbocaZon carbocaZon

poor orbital overlap

Me Me for migraZon
Me 1 Me Me 1 Me
1 migraZon Me Me
2 2 2 would lead to 1
7
6
3
7 3
7 3 4-membered Me
6 5
5 4 5 4 6 ring 2 8 best orbital overlap
Me Me
8 8 5
4 for migraZon (ca.
H Me 3 4
8 co-planar)
7 6
orbital overlap σC-C
into empty p-orbital H
Rearrangements and Reactive Intermediates 15

Wagner-Meerwein rearrangements exemplified – Nature was here before us – biosynthesis of camphene

Me Me Me Me Me 1 Me
Me Me 1 Me
linalyl 2 Me 1
2
2 3
pyrophosphate - OPP 7 3
6 5
4 6
7
3
6 4 5 4
5
Me Me
7 8
O O 8
P P O Me Me Me 8
O O form 2° caZon
O O form 3° caZon form 3° caZon
relief of ring strain
pyrophosphate, or
diphosphate – PPO. 7 7 Me Me Me Me
1 1
PPO is a good leaving 2 1 2
Me 2 2
3 Me 3 1 7
group c.f. TsO -H
6 5 3
6
7
3
4 6 5 Me 4 6 5 Me 4 5 4
Me 8 Me Me
8 8 8

Wagner-Meerwein rearrangements exemplified – Nature was here before us – biosynthesis of lanosterol

(precursor or cholesterol)
Me Me Me Me
Me
chair – boat – chair
conformaZon Me Me H Me
Me H Me Me H Me Me
H Me Me Me Me Me
O
HO H HO H
H Me
Me Me Me
H Me H Me H H

squalene oxide two 1,2-hydride shi`s lanosterol

two 1,2-methyl shi`s
conformaZon of squalene oxide controlled by enzyme (lanosterol synthase) – reacZon occurs via discrete
carbocaZon intermediates and is not concerted
Rearrangements and Reactive Intermediates 16

Pinacol and semi-pinacol rearrangements

mechanism in more detail
pinacol pinacolone correct orbital overlap required for migraZon
O
HO OH Me H
H Me CH3
HO Me O
Me Me Me
Me Me Me CH3
Me H
Me Me
Me
nO to σ*C-C
H -H
H
CH3
O
HO OH 2 HO Me OH H CH3 σC-C to empty p
Me Me
Me Me Me Me
Me Me Me Me Me
Me

useful method for the preparaZon of spirocyclic ketones.

HO H 2O
H -H
OH OH OH OH O

the starZng diols can be readily prepared by the pinacol reacZon

Mg Mg
O O O O O O HO OH
Mg Mg 2 H 2O
• • •
SET

epoxides and halohydrins can be substrates for the pinacol rearrangement

Rearrangements and Reactive Intermediates 17

semi-pinacol rearrangements – the Tiffeneau-Demayanov reacZon

i) CN NH 2 N2 OH O
O HO HO
ii) LiAlH 4
or HNO 2 -H

i) CH3NO 2. EtO
ii) LiAlH 4

semi-pinacol rearrangements - stereochemistry

H
OH
nO to σ*C-C H C-C H
HNO 2 migration tBu
O tBu
tBu N2 O O
tBu NH 2
H H
σC-C to σ*C-N H H H
H
O
OH nO to σ*C-C C-C H
HNO 2 migration
H tBu
tBu N2 tBu O O
tBu NH 2
H
σC-C to σ*C-N H
H H H
H
nO to σ*C-H 1,2-hydride O
OH C O
HNO 2 O shift
tBu H tBu H
tBu NH 2
H
σC-H to σ*C-N H
tBu
N2 H
OH O
epoxide
OH HNO 2 formation H O
H tBu
tBu H tBu
H
tBu NH 2
H
nO to σ*C-N H
N2

anZ-periplanar bonds means best overlap of σ and σ* orbitals

Rearrangements and Reactive Intermediates 18

the dienone-phenol rearrangement – formally the reverse of the pinacol rearrangement

the dienone-phenol rearrangement can be mechanisZcally complex but can also just involve a simple 1,2-shi` of
an alkyl group
O OH OH OH OH

H
Me
Me
H
Me Me Me Me Me Me Me Me

the pinacol rearrangement is driven by formaZon of a strong C=O bond

the dienone-phenol rearrangement involves loss of a C=O bond and gain of an aromaZc ring

the dienone-phenol rearrangement provides a method for ring annulaZon

OH O O OH
tBuO H
Cl Cl
Rearrangements and Reactive Intermediates 19

Theory of 1,2-shiHs retenZon retenZon

curly arrow mechanism R' R''
R' R'''
R'' R'
R''' R'''
R''
R R R R
R R
R R R R
orbital descripZon R R

C C C
R R R R 3-centre-2-electron system
at the transiZon state
R R
R R R R
R R

in the transiZon state we have three orbitals and two electrons to distribute c.f. the allyl caZon

ψ3 R R
ψ3 R R
R R
ψ3
R R

• ψ2 R R
R R
ψ2
R R ψ2
R R

ψ1
R R ψ1 R R ψ1
R R
R R

allyl caZon 1,2-shi` transiZon state 1,2-shi` transiZon state

(carbocaZon) (carbanion)
Rearrangements and Reactive Intermediates 20

1,2-caZon and 1,2-anion shi`s

overall for carbocaZon 1,2-shi`, transiZon state has net bonding
R R the transiZon state has 2 electrons cyclically conjugated in a ring
ψ3
R R and is therefore aromaZc – more of this next year
1,2-shi`s occur with retenZon of configuraZon in the migraZng
R R group
ψ2
R R the 3-centre-2-electron structure may be a transiZon state or a
high energy intermediate

R R ψ1
as we have seen, concerted migraZon with loss of the leaving
group is another mechanisZc possibility
R R
1,2-shi` transiZon state
carbocaZon take home message – 1,2-shi`s easy for carbocaZons,
difficult for carbanions and radicals

R R
ψ3 both ψ2 and ψ3 are anZbonding
R R

therefore 1,2-shi`s of carbanions and radicals would be

R R expected to be far less favourable (ψ2 is occupied)
ψ2
R R
transiZon state for 1,2-shi` of carbanions has 4 electrons R' R''
cyclically conjugated (ψ12ψ22) in a ring and is anZ-aromaZc
R'''
R R ψ1
one can also view the difficulty of 1,2-carbanion shi`s arising R
R R
from the geometrical impossibility of the carbanion performing R
R
1,2-shi` transiZon state an intramolecular SN2 reacZon with inversion of configuraZon
R
carbanion
Rearrangements and Reactive Intermediates 21

as we have seen, for efficient rearrangement orbital alignment is criZcal

H H
all three indicated hydrogen atoms are in the same H
H
plane - rearrangement to the more stable 3° carbocaZon
does not occur H

retenZon of configuraZon at the migraZng centre is observed

Me Me Me Me Me Me
NH 2 HNO 2 N2 H 2O HO
Me Me Me Me
Me Me
Me Me
migraZon with 98% Me Me
retenZon of configuraZon

at the migraZng terminus inversion or racemisaZon can occur

racemisaZon will occur if the mechanism is SN1-like i.e. via a full carbocaZon

HO OH H H 2O OH Et OH Et O
Et Et H
Me Me Me H Me H
enanZopure racemic

inversion at the migraZng terminus will occur if the mechanism is concerted

Rearrangements and Reactive Intermediates 22

Concerted Rearrangements
Neighbouring group parZcipaZon (NGP)

DefiniZon (IUPAC): the direct interacZon of the reacZon centre (usually, but not necessarily, an
incipient carbenium centre) with electrons contained within the parent molecule but not
conjugated with the reacZon centre – could be lone pair, π-bond, or σ-bond

A rate increase due to neighbouring group parZcipaZon is known as 'anchimeric assistance’
neighbouring group par4cipa4on and anchimeric assistance are oKen used interchangeably
meso Br HMe

H enanZomers
Me Br
Br HMe
HBr Br HMe Br same relaZve
H H H H inversion configuraZon as
Me OH Me OH 2 inversion Me Me
Me H Br starZng material
H racemic product
diastereomeric Br Br Me
single enanZomer
bromohydrins
C2 symmetric Br Me H

H
Me H Br Me H Br Me Br
Br
HBr same structure
H H H Me inversion meso - achiral
Me OH Me OH 2 inversion Me H
Me H Br
Me
Br Br H

outcome of above reacZons is excellent evidence for symmetrical intermediates and hence
neighbouring group parZcipaZon
Rearrangements and Reactive Intermediates 23

why do these single enanZomer tosylates undergo solvolysis at significantly different rates to give racemic product?
non-classical carbocaZons, A.K.A. carbonium ions
rds
AcOH AcOH NGP
H OAc + AcO OTs
krel = 1 krel = 350
endo-Ts OTs H
racemic
H H
exo-Ts
rds
no NGP 3
5
6 4
4 5
7
H 3 2
OAc 7 6 1
1 2
H AcO
non-classical
O O
carbocaZon -
H carbonium ion
Me OH AcO Me OH
H AcO

alternaZve perspecZve of NGP exo-Ts reacts faster due to NGP of anZperiplanar C-C
1.8 Å sigma bond
endo-Ts ionises slower to give classical carbocaZon
H
followed by non-classical carbocaZon formaZon
TsO 3-centre-2-electron bonds non-classical caZon has plane of symmetry leading to
racemic products

Rearrangements and Reactive Intermediates 24

evidence for non-classical carbocaZon (carbonium ion) over equilibraZng carbenium ions for the 2-norbornyl caZon
i.e. is the non-classical caZon an intermediate or TS?

low temperature 13C NMR (5 K) shows a symmetrical ion

X-ray crystal structure (Science, 2013, 341, 62) provided definiZve evidence of bridged structure

1.8 Å

δC 125 ppm

Br3AlBrAlBr3
Note: non-classical carbocaZons are only formed if they are more stable than their classical counterparts
The 1,2-dimethylnorbornyl caZon is a rapidly equilibraZng species with parZal σ-
delocalisaZon.
X-ray structure of the analogous tetramethylnorbornyl caZon also demonstrates parZal
σ-delocalisaZon.
2.1 Å Me
1.7 Å
Me
Me
Me Me
Me Me
Me F5SbFSbF5
Rearrangements and Reactive Intermediates 25

π-bonds are be"er donors than σ-bonds J Ph

OTs Me
AcOH
krel = 107 Me

Me
O
HO H
TsO AcO OAc
SbF6 SbF6
krel = 1
classical carbocaZon same structure J. Am. Chem. Soc., 1989, 111, 9224
(carbenium ion)
Me
O
TsO HO AcO

krel = 1011 non-classical carbocaZon complete retenZon of configuraZon

(carbonium ion) (double inversion)

OTs H H
HH
AcOH

krel = 104 H H OAc

allyl caZon
Rearrangements and Reactive Intermediates 26

More neighbouring group parZcipaZon with π-bonds – phenonium ions

meso phenonium ion

(σ-plane)
Me H

Me
Me H H OAc enanZomers
AcOH
racemic product
Me Me Me inversion
H OTs inversion H H
H Me
O 133 ppm
AcO
Me 155 ppm
Me OH H
diastereomeric 172 ppm
single enanZomer
substrates C2-symmetric 69 ppm
phenonium ion
δC = 60 ppm
H Me

H Me Me
AcOH H OAc same single
Me Me H inversion enanZomer product
H OTs inversion H Me
H Me
O
H
Me OH AcO Me
Rearrangements and Reactive Intermediates 27

mulZple 1,2-shi`s

Me OH Me Me Me
HO
H H 2O

-H

H - H 2O

Me Me Me Me

formaZon of adamantane

Me
Me
Diels-Alder Br AlBr3
H 2, Pd
heat

C10H16 adamantane C10H16

all C10H16 hydrocarbons rearrange to adamantane on treatment with Lewis acid

adamantane is the thermodynamically most stable C10H16 isomer – it possess repeaZng units of the
diamond lacce
Rearrangements and Reactive Intermediates 28

transannular hydride shi`s

HO Me Me Me D
H -H
- H 2O
HO D HO D O

δH = +4.0 ppm
cyclodecyl caZon – 3-centre-2-electron bond c.f. diborane 1
H H H
Me H Me
B B
SbF5, FSO 3F H H H
H
-140 °C 3
HO Me Me
δH = -3.9 ppm δC = 142 ppm δH = -0.51 ppm
6 5

δH = -6.85 ppm
Cl
H
δC = 153 ppm
SbF5, FSO 3F
or or H
-140 °C
δH = +6.80 ppm H
H
1,6-caZon slightly
H higher in energy than
H
1,5-caZon
Rearrangements and Reactive Intermediates 29

Carbanion rearrangements – carbanions are much less prone to rearrangement than carbocaZons
1,2-aryl shi`s

2Li, -60 °C CO 2
Ph Ph Ph
Ph Cl -LiCl Ph Li Ph CO 2H

0 °C

Ph CO 2 Ph
HO 2C
Ph Ph
Ph
Ph
delocalised therefore
more stable carbanion

X-ray structure
evidence for spirocyclic intermediate
Me Me Me Me
Me Me Me Me
Me Me CO 2H Me Me Cl Me Me Me
Me Li, -75 °C Me Cs-K-Na alloy CO 2
Me Me Me
then CO 2 -75 °C

Ph Ph Ph Ph CO 2H
Ph
3° carbanion delocalised, dearomaZsed carbanion
more stable than 3° carbanion
Rearrangements and Reactive Intermediates 30

Favorskii rearrangement
O O OMe O OMe O OMe overall in the Favorskii
Cl NaOMe MeOH SE1 rearrangement an alkyl group
(R) moves from one side of the
carbonyl group to the other
NaOMe 2-electron electrocyclic ring O O
closure - more of this next year R' R''O R'
R R''O
O O OMe
O O X R
Cl

oxyallyl caZon

symmetrical intermediate established by Lo}ield with doubly labelled substrate = 14C label

O O O O OMe O OMe
O OMe
Cl NaOMe MeO MeOH
1:1
mixture
MeOH
Rearrangements and Reactive Intermediates 31

quasi-Favorskii rearrangement – Favorskii rearrangement on substrates with no enolisable hydrogen atoms

O O O
Cl Cl OH
HO
Ph Ph OH
Ph
MeN MeN MeN

the mechanism is a base catalysed semi-pinacol rearrangement and is closely related to the mechanism of the
benzil-benzillic acid rearrangement

Ramberg-Bäcklund reacZon

O O
S
O O O O
O O S
S Cl NaOMe S Cl cheletropic extrusion of SO2
– more next year

concerted 1,2-shi`s of carbanions are geometrically impossible - as the carbanion R' R''
cannot reach to perform an intramolecular SN2 reacZon with inversion of configuraZon R'''
R
R
R
R
Rearrangements and Reactive Intermediates 32

Concerted 1,2-shi`s of carbanions are geometrically impossible - as the carbanion

X
R' R''
cannot reach to perform an intramolecular SN2 reacZon with inversion of configuraZon
R'''

1,2-Shi`s of carbanions occur by a radical mechanism – 1,2-Wicg, 1,2-Stevens and related R

rearrangements. R
R
R
1,2-Wicg rearrangement
Me

solvent cage • Me
Me
Me • Me •
Me BuLi
O O O O OH
•

Stevens rearrangement

O Me Me O Me Me O Me O Me O Me
N HO N N N N
Ph Ph Ph
• Me
Ph • •• Me Ph Me

•
•

solvent cage