Winstein: Concept of ion pairs

contact or tight ion pair

Intimate Ion Pair Inversion of Configuration

Solvent Separated Ion Pairs Partial Racemization

Dissociated Ions Racemization

The ion-pair concept thus predicts that SN1 reactions can display either complete
racemization or partial inversion.

Acetone/water (8:2) Acetone/water (8:2)

k ex
Intimated and Solvent Ion Pairs  2.3 Dissociated Ions
k rac
The fact that the rate of isotopic exchange exceeds that of racemization indicates
that ion pair collapse occurs with predominant retention of configuration.
 About one-fifth of the ion pairs recombine rather than react with the
nucleophile. A similar experiment in acetic acid indicated about 75% internal
return.
• Ion pair formation and recombination is occurring competitively with ion pair
formation and substitution.

A study of the exchange reaction of benzyl tosylates during solvolysis in several solvents showed that with
electron-releasing group (ERG) substituents, e.g., p-methylbenzyl tosylate, the degree of exchange is quite
high, implying reversible formation of a primary benzyl carbocation. For an electron-withdrawing group
(EWG), such as m- Cl, the amount of exchange was negligible, indicating that reaction occurred only by
displacement involving the solvent. When an EWG is present, the carbocation is too unstable to be formed
by ionization.
This study also demonstrated that there was no exchange with added “external” tosylate anion,
proving that isotopic exchange occurred only at the ion pair stage.
Demonstrating the ion pair return

The rate of decrease of optical rotation (racemisation) is greater than the rate of
product formation.
The solvent-separated ion pair is the most likely intermediate to play this role.

Special Salt Effect:

• Addition of salts typically causes an increase in the rate of solvolysis of 2° alkyl
arensulfonates that is linear with salt concentration (due to the increase in dielectric
constant of the medium).

• The addition of LiClO4 or LiBr in the acetolysis of certain tosylates produced an initial
steep rate acceleration that then decreased to the normal linear acceleration (caused
by the ordinary salt effect).

• This is interpreted as follows: the ClO4- (or Br-) traps the solvent separated ion pair to
give R+ ClO4- which, being unstable under these conditions, goes to product. Hence,
the amount of solvent-separated ion pair that would have returned to the starting
material is reduced, and the rate of the overall reaction is increased.
 Carbocation Generation
Carbocation Generation

Removal of an energy-poor anion from a neutral precursor via Lewis Acids

R3C X + LA R3C + LA–X LA: Ag , AlCl3, SnCl4, SbCl5, SbF5, BF3, FeCl3, ZnCl2, PCl3, PCl5, POCl3 ...
X: F, Cl, Br, I, OR

Acidic dehydratization of secondary and tertiary alcohols

- H2O R: Aryl + other charge stabilizing substituents

R3C OH + H–X R3C + X
X: SO42-, ClO4-, FSO3-, CF3SO3-

From neutral precursors via heterolytic dissociation (solvolysis) - First step in SN1 or E1 reactions

solvent
R3C X R3C + X Ability of X to function as a leaving group:
-N2+ > -OSO2R' > -OPO(OR')2 > -I • -Br > Cl > OH2+ ...

Addition of electrophiles to š-systems

R R H R R H R
H R R R
R R R R H

Hydride abstraction from neutral precursors

H H RS R2N
+ Lewis-Acid H H
R3C H R3C R3C H = etc.
H H H H
RS R2N

Lewis-Acid: Ph3C BF4, BF3, PCl5

 Carbocation Stability
Carbocation Stability
Stability: Stabilization via alkyl substituents (hyperconjugation)

Order of carbocation stability: 3Þ>2Þ>1Þ

R H H H
> H C > H C Due to increasing number of substituents
R C > R C
capable of hyperconjugation
R R R H Electrons in C—C bonds are more
polarizable than those in C—H bonds;
therefore, alkyl groups stabilize
The relative stabilities of various carbocations
Hydride ion
carbocations better than H.
can be measured in the gas phase by their affinities
affinity for hydride ion.
CH3+ 314
CH3CH2+ 276
R + H R–H + HI
(CH3)2CH+ 249
Hydride Affinity = –G° (CH3)3C+ 231
HI increases  C(+) stability decreases H2C=CH+ 287
H C C+ 386
Note: As S-character increases, cation stability PhCH2+ 239
decreases due to more electronegative carbon. Carbocation Subclasses
J. Beauchamp, J. Am. Chem. Soc. 1984, 106, 3917.

Carbon-substituted Heteroatom–stabilized
R1  R  R
R1 O N

R3  R2 R3 R2 R3 R2

R–R3 = alkyl or aryl R–R3 = alkyl or aryl R–R3 = alkyl or aryl

 Carbocation
CarbocationStability
Stability

Vinyl & Phenyl Cations: Highly Unstable

+21 +81
H3C CH2 H2C CH HC C
276 287 386 Hydride ion affinities (HI)

+11
H2C CH Phenyl Cations
287
298

Allyl & Benzyl Carbocations

Carbocation Stabilization via -delocalization

Br

Stabilization by Phenyl-groups
The Benzyl cation is as stable as a t-Butylcation. This is shown in the
subsequent isodesmic equations:

Hydride ion affinities (HI) Ph CH2 Me3 C

239 231
The Allyl–
-Silicon Effect
& Vinylsilanes react with electrophiles

R3Si E E "R3Si+"
E
SiMe3 "R3Si+"
E

Mechanism - the simple picture: -Silicon stabilizes the carbocation

E Nu
R3Si R3Si E E

Nu
SiMe3 H2C SiMe3
E

E E
 Reactions
Reactionsof Allylsilanes
of Allylsilanes

Allylsilanes add to aldehydes and acetals under Lewis acid promotion

OH
O
Me3Si Ph TiCl4
+ n-C3H7
H Me
Ph regioselectivity: Allyl inversion
O OH
Me3Si TiCl4 Ph
+ n-C3H7
H Me
Ph

Felkin Selectivity also holds with this class of nucleophiles

OCH3
Acetals can be used as well OCH3
Me3Si Me TiCl4
+ n-C4H9
H3CO n-C4H9 (80%)
Me Me Me
OCH3 OCH3
Me3Si TiCl4
+ Me
H3CO n-C4H9 (83%) n-C4H9
Me Me Me

The Sakurai Reaction (Enone Conjugate Addition)

O

OTiCl4 Me
O
TiCl4 Me
Me CH2Cl2 75%

SiMe3 O
Me3Si Me
Me3Si
Fleming, Org. Reactions 1989, 37, 127-133
17%
 Carbocation [1,2] Sigmatropic Rearrangements
Carbocation Rearrangements: [1,2] Sigmatropic
1,2 Sigmatropic shifts are the most commonly encountered cationic rearrangements. When
either an alkyl substituent or a hydride is involved, the term Wagner-Meerwein shift is
employed to identify this class of rearrangments.

Stereoelectronic requirement for migration....

retention of stereochemistry

C C
A D A D
B bridging T.S. B

C
A D
B
 Carbocations in Bridged Systems
Carbocations and Solvolysis Rate
Solvolysis rates represent the extend of that cyclopropyl orbital overlap
contributing to the stabiliziation of the carbenium ion which is involved as a
reactive intermediate:

OTs
Me OTs
Cl
Me
krel = 1 krel = 1 krel = 1

OTs
OTs

Cl

krel = 106 krel = 108 krel = 10-3

Me
Me OTs why so
Me reactive?
TsO TsO TsO

-7 -13 4
Perfect Bond Alignment
 Demjanov-rearrangement (Driving force: relief of ring strain)

Me H
Me
Me
H2SO4 H
Me Me Me
Me OH H Me

Me H OH
Me
Me
H H
equiv to Me Me
HO Me
Me H Me
E. J. Corey J. Am. Chem. Soc. 1964, 86, 1652. -caryophyllene alcohol
Synthesis of (±)-Isocomene

Me Me
Me Me Me Me
Me
H+
Me Me Me
Me
Me Me
Me Me
(±)-Isocumene

Pirrung, JACS 1979, 7130; 1981, 82.

The Norbornyl Cation and Non-Classical Carbocations

Optically Active Exo Brosylate → Exo Product

(100% racemization)
 Nonclassical Carbocation

These bridged carbocations, involve delocalization of electrons and formation of

three-center, two-electron bonds, and are sometimes called nonclassical ions.

The description of the nonclassical norbornyl cation developed by Winstein

implied that the bridged ion is stabilized relative to a secondary ion by C−C
bond delocalization.