D. A.

Evans

Carbocations: Stability & Structure

Chem 206

http://www.courses.fas.harvard.edu/colgsas/1063

Chemistry 206
Advanced Organic Chemistry

Olah, G. A. (2001). 100 Years

of Carbocations and their
Significance in Chemistry. J.
Org. Chem. 2001, 66, 59445957. (handout)
Walling, C. (1983). An Innocent
Bystander Looks at the 2-Norbornyl
Cation.
Acc. Chem. Res. 1983, 16, 448.
(handout)

Carbocation Stabilization

Carbocation Structures by X-ray Crystallography

Vinyl & Allyl Carbonium Ions

Reading Assignment for this Lecture:

Carey & Sundberg, Advanced Organic Chemistry, 4th Ed. Part A
Chapter 5, "Nucleophilic Substitution", 263-350 .
Birladeanu, L. (2000). "The Story of the Wagner-Meerwein Rearrangement.
J. Chem. Ed. 2000, 77, 858. (handout)

March, Advanced Organic

Chemistry, 4th Ed. Chapter 5,
pp165-174.
Lowery & Richardson, Mech.
& Theory in Org, Chem., 3rd Ed.
pp 383-412.

Laube (1995). X-Ray Crystal

Structures of Carbocations Stabilized
by Bridging or Hyperconjugation. Acc.
Chem. Res.1995, 28,: 399 (electronic
pdf)

Arnett, Hoeflich, Schriver in

Reactive Intermediates Vol 3,
Wiley, 1985, Chapter 5, p 189.

Lecture Number 33

Introduction to Carbonium Ions

Other Relevant
Background
Reading

Monday
D. A. Evans
11, 2006

December

Saunders, M. and H. A.
Jimenez-Vazquez (1991).
Recent studies of
carbocations. Chem. Rev.
91: 375.

Stang, P. J. (1978). Vinyl

Triflate Chemistry:
Unsaturated Cations and
Carbenes. Acc. Chem. Res.
11: 107.
Olah, G. A. and G. Rasul (1997).
Chemistry in superacids .26. From
Kekule's tetravalent methane to five-,
six- and seven-coordinate protonated
methanes. Acc. Chem. Res. 30(6):
245-250.
Olah, G. A. (1995). My search for
carbocations and their role in
chemistry (Nobel lecture).
Angew. Chem., Int. Ed. Engl. 34,
1393-1405

Problem 17: The reaction illustrated below was recently reported by Snider and co-workers (Org.
Lett. 2001, 123, 569-572). Provide a mechanism for this transformation. Where stereochemical
issues are present, provide clear three dimensional drawings to support your answer.
O
Me

EtAlCl2
CH2Cl2, 0 C

Me

OH

CHO

NH2

Carey & Sundberg-A, p 337: Provide

mechanisms for the following
reactions.

O
R

Me

NaNO2

HOAc/H O
2

M. Shair, D. Evans

Carbocation Generation & Stability Chem 206

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

Carbocation Stability: The pKR+ value

+

R + H2O

Definition:

ROH + H

R+

ROH

aR+

aH+
a

a = activity

H2O

pKR+ = log KR+

PCl5
(4-MeO-C6H4)3C
0.82

Ph3C
6.63

Fe

(3-Cl-C6H4)3C
11.0

CHPh

CH2

Fe

0.40

Ph

0.75

13.3

CHPh R
Cr(CO)
10.4

Co2
3

7.4

H7 C3
+

HC
7

3 7.2

C3H7

most stable

Carey & Sundberg, A, pp 276-

4.77

Carbocation Generation
Hydride abstraction from neutral precursors
R3C H +

Lewis-Acid
H

R3C H =

H
H

RS
RS

RC

LAX

Acidic dehydratization of secondary and tertiary alcohols

Lewis-Acid: Ph3C BF4, BF3,

salts

LA

LA: Ag , AlCl3, SnCl4, SbCl5, SbF

BF3Br,
, FeCl
3, ZnCl2, PCl3, PCl5, POCl3 ...
5, Cl,
X: F,
I, OR

Carey & Sundberg, A, p 277

Table: pKR+ values of some selected carbenium

RCX +

R
:
A
r
yl
+
o
t
h
e
r
c
h
a
r
g
e
s
t
a
b
ili
zi
n
g

su
bst
itu
ent
s
X:
SO
4

2-

,
Cl
O4
-

,
FS
O3
-

,
CF
3S

O3
-

From neutral
precursors via
heterolytic
dissociation

(solvolysis) - First step in SN1 or E1 reactions

R3C

solvent

R3C X

+ X

Ability of X to function as a leaving group:

+
-N > -OSO
R' > -OPO(OR') 2 > -I ! -Br > Cl > OH
2

Addition of electrophiles to !-systems

R

H
H

R
R

R
H

Problem 897: Provide a Mechanism of this transformation

H2SO4
HC

C CH2OH

Br

Carbocations: Structure

D. A. Evans, B. Breit

Carbocation Stabilization Through Hyperconjugation

R

H
C

H C

H
C

FMO Description
Take linear combination of CR (filled) and C pz-orbital (empty):
E

CR

CR

CR

C
H

CR

Syn-planar orientation between interacting orbitals

Chem 206

D. A. Evans, K. Scheidt

Me

Me

F
Me
H

Me

Carbonium Ion X-ray Structures: Bridged Carbocations

Me

+
2 SbF5

[F SbFSbF ]
5

Me
H
Me

Me

T. Laube, Angew. Chem. Int. Ed. 1987, 26, 560

Chem 206

Ph

Ph

Cl

Me
Me

AgSbF6

Me
Me
F Sb
5

SbF

1.495

2.092

1.739 **

1.467

+
1.467
1.855

1.442

**One of the longest documented CC bond

lengths.

C
C
hyperconjugation
no bridging

1.50
3

T. Laube, JACS 1989, 111, 9224

D. A. Evans, K. Scheidt

Carbonium Ion X-ray Structures: A Summary

66

1.442

1.446

+
1.43
9

1.508

1.
34
2

1.421
1
.
4

Chem 206

(ref 1.513 )PhC(Me)=CH2

1.408

2.092

+
1.432

1.371

1.491

1.467

1.739

+
1.442

1.668
Cl

1.432
1.422
Cl

1.725
1.467 1.495

+
1
.
8
5
5

1.621

98.2

1.622

1.608
Nomenclat
ure:
classical
vs
nonclassic

1.503

al
1.551

CC

C
C

s
y
m
m
e
t
r
i
c
hyperconju
a
opengation
unsymmetrical l
b
r
i
d
g
i
no
n
trivalentbridging
bridging
g
increasin
g
nonclass
ical
characte
r

cla
ssi
cal

C
C

n
o
n
c
l
a
s
s
i
c
a
l

D. A. EvansChapter 18: Chemistry of Aryl & Vinyl Halides

Chem 30

Substitution Reactions
Substitution (SN1)
R

Favorable

R
Me

H C

Unfavorable

Me

H
X

H2C

H
Sp hybridized Carbon
is more electronegative

CSp2 Carbonium Ions do exist!

Si
1.221

1.946
Si
Me

Si

Si

Me

Me

Me
CMe3

Normal CC triple bond lengths are ~1.21

D. A. Evans, B. Breit

Vinyl & Allyl Carbocations

Chem 206

Vinyl &
Phenyl
Cations:
Highly
Unstable
Eviden
ce
sugge
sts
that
vinyl
cation
s are
linear.

g size decreases, the rate of

hydrolysis also diminishes. Implying
that the formation of the linear vinyl
cation is disfavored due to
increasing ring strain.

orbital retains
sp character.
Additionally, the empty orbital lies
in the nodal plane of the ring,
effectively prohibiting conjugative
stabilization.

A secondary kinetic isotope effect

R

was measured to be KH/KD = 1.5

(quite large) indicating strong
hyperconjugation and an
orientation of the vacant p orbital
as shown above.

Hydride ion

OS

allyl cation

Stabilization by Phenylgroups
The Benzyl cation is
approximately as stable as a tButylcation.

affinities (HI)
+21

H3 C

CH2
276

+11
H2 C

r
i
n

R
R

P. J. Stang J. Am. Chem Soc. 1971, 93,

1513; P. J. Stang J.C.S. PT II 1977, 1486.

HOSolv

A
s

Carbocation
Stabilization via delocalization

OTf

olv

Allyl & Benzyl

Carbocations

CH

287

(CH3)3C + PhCH3

(CH3)

(CH3)3C + PhCH2Cl

(CH3

Hydride ion affinities (HI)

Ph

298

The
ring
geometry
opposes
rehybridization (top) so the vacant

Hydri
de
ion
affinit
ies
versu
s
Rates
of
Solvo
lysis

HI
-HI
Relative
Solvolysis
rates in 80%
EtOH, 80 C

D. A. Evans The Johnson Longifolene Synthesis

Chem 206
Ho, Nouri, Tantillo,
JOC 2005, 70, 51395143

Volkman, Andrews, Johnson, JACS 1975, 97, 4777

The Cationic Cascade

Route to Longifolene

The plan ( According to Volkman):

Me Me

HO

Me

Me

Me

Me

Me

W. S. Johnson!s total synthesis of the

sesquiterpenoid longifolene is a classic
example of the power of cationic
polycyclizations for constructing complex
molecular architectures. Herein we revisit the
key polycyclization step of this synthesis using
hybrid Hartree-Fock/density functional theory
calculations and validate the feasibility of
Johnson!s proposed mechanism. We also
explore perturbations to the 3-center 2 electron
bonding array in a key intermediate that result
from changing the polycyclic framework in
which it is embedded.

75%
CH2

TFA, K2CO3

longfifolene
Me Me

HO

ZnBr2
NaBH3CN
94%

HO
Me
H

CH2

Me

steps

ZnBr2

longfifolene

Me
Me Me

Me

Me Me

Me
Me

Me Me

Me Me

Me

Me

FIGURE 1. Relative
energies (kcal/mol) of
stationary points for the
mechanism shown in
Scheme 2 (B3LYP/631G(d) zero-point corrected
energies in italics,
B3LYP/6-31G(d) free
energies at 0 C in bold,
and CPCM-B3LYP/631G(d) energies in water
underlined).

D. A. Evans, B. Breit

Cyclopropyl-carbinyl & Bridgehead Carbocations

Carbocation Stabilization via Cyclopropylgroups

Chem 206

24

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:
O
T
s

See Lecture 5, slide 5-05 for discussion of Walsh orbitals

Me OTs

Me

A rotational barrier of about

13.7 kcal/mol is observed in
following example:

Cl

NMR in super acids

Me

(CH3) = 2.6 and 3.2 ppm

X-ray Structures support this orientation

1.302

Mek

rel

=1
OTs

O
1.517
1.478

1.222

krel = 10

1.474

CareyA, p 286

Bridgehead
Carbocation
s

1.464

1.541

Me

1.409

Me

OTs
Me

1.444
1
1.534

TsO

10-7

Bridgehead carbocations are highly disfavored due to a strain increase in

achieving planarity. Systems with the greatest strain increase upon passing
from ground state to transition state react slowest.

TsO

why so reactive?

TsO

R. F. Childs, JACS 1986, 108, 1692

D. A. Evans, J.Tedrow A Stable Hypervalent Carbon Compound ?

Chem 206

"The Synthesis and Isolation of Stable Hypervalent Carbon Compound (10-C-5) Bearing a 1,8-Dimethoxyanthrecene Ligand"
Akibe, et al. JACS 1999, 121, 10644-10645

Me MeO
CO Me
OMe

OMe
Me

OMe

Me3O BF4

O C

B F
2

"The relevant CO distances are longer than a covalent CO bond (1.43 ) but shorter than
the sum of the van der Waals radii (3.25 )."
2.428

1.483

2.428

2.452
2.45
2

For a recent

monograph on see emistry of Hypervalent

hypervalent
: Compounds", K. Akiba, WileyCompounds
"Ch VGH, 1999