651.

06

Carbocations
terminology: historically, R3C was referred to as a carbonium ion but:
C

vs
carbonium
(hypervalent)
5 bonds to C -rare

carbenium
(hypovalent)
3 bonds to C -commonplace

moot point until the advent of super acids (George Olah, Nobel 96)
CH4

FSO 3H - SbF5

CH5

SO2 (l)

SbF6

methanonium
ion

"super acid"
(also HF - SbF5)

ex:

- H2

CH3

extremely non-nucleophilic,
non-basic counterion

(see Olah, JACS 1972, 94, 808; CHEMTECH 1971, 1, 566)

structure:
empty p orbital
R'' C

R'
R

quite standard sp2 hybridization

sp2 hybridized

planar structure

C
HH

H
3 - center, 2e- bond

note: it lacks an octet unstable

What about

?
H

-cant rehybridize to give empty p orbital

114

empty sp 2 orbital (very unstable)

651.06
contrast this with benzenonium ion:
H
H
H

H
H

H
H

and benzyl cation:

H

H
H

H
H

stability:
+18 +27 +38 kcal
3o > 2o > 1o > CH3

general trend:

(due to hyperconjugation of C-H bonds)

R3Si
CH2

special case:

very stable (hyperconjugation of C - Si)

>

extra stability:

>

(resonance)

~ (CH3 )3C

R'
R

overlap of empty p orbital with cyclopropyl

p orbital
special case:
Br

Br

tropylium ion - very stable

(Doering, JACS 1954, 76, 3203)

O

- heteroatom:

>

>

115

(CH3)3 C

Y = Cl < OR < NR2 < SR

651.06
Why this order?
Y

consider resonance:

so, order is dictated by a balance of electronegativity & bond energy

Why is Y C so stable when Y is more electronegative than C?
Y C is hypervalent, not hypovalent has a full octet
unstable cations:

bridgehead carbocations (cant planarize)

RC C

-sp2, sp carbocations (cant empty a p orbital)

hypovalent heteroatoms ( R O

, R N , etc.)

Non - Classical Carbocations

used to describe carbocations stabilized by 3-center, 2e- interactions

ex:

question: what is the structure of the cation? 1 2 or 3?

The answer to this question has been debated for 35 years
players: Winstein (3) vs. Brown (1 2)
We will discuss this question more later on ...

116

651.06

Methods of Generation of Carbocations

1) Ionization by heterolytic bond cleavage
C Y

LA

Y LA

Y = Cl, Br, I, OR, SR

LA depends on Y
Y

LA
Ag+, FeX3, AlX3, SnX4 (F with SbF5)

Cl, Br, I
OR

TiCl4, TMS-OTf, TMS-I, BF3, R2AlCl; H+, Li+, Sc3+, Yb3+, Eu2+

SR

Hg++, Cu+

Example:
O

OCH3

BF3OEt2

2) Addition of an electrophile to a multiple bond

E

alkenes:
E+ = H+, X+, RSe+, RS+, R3C+, Pt+
E

E+

TiCl4, Sn(OTf)2, BF3, TMS-OTf, Et2AlCl, H+

HgCl2, Hg(BF4)2

NR

BF3, TiCl4, Yb(OTf)3, Sc(OTf)3

Example:
O

BF3

BF3OEt2

117

BF3

651.06
3) Hydride abstraction (very exotic)
FSO 3H - SbF5

R 3C H

CR3

SO2 (l)

H2

SbF6

Olah, JACS 1967, 89, 4739

Reactions of Carbocations
1) Nucleophilic attack
R3C

:Nuc

R3C-Nuc

:Nuc = ROH, RSH, X , alkene (produces new carbocation), Ar

note: this is the opposite of ionization (#1 of previous section)
2) - elimination
H

also:

Nuc:
SiR3

Nuc:
SnR3

note: this is the opposite of generation method #2

118

651.06

3) Rearrangements
H

1,2 hydride shift - favors more stable cation (VERY fast reaction)
CH3

H 3C

Wagner - Meerwein shift (less fast, but still fast)

Wagner-Meerwein rearrangement is an equilibrium reaction;
ex:
B:
OH

OH2
H2SO 4

H
- H2 O
H

H
B:

+
H

+
H

(note: this is not a good thing if youre trying to synthesize something!)

Carbanions

occurs as a complex with M, either ionic or covalent

M = Li, Na, K, MgIX, CuI, ZnIIX, CeIIICl2, CrIICl, Al3+

119

651.06
structure:
sp 3 orbital
sp 3 hybridized
1

R2

R2
1

C R3

R3

-rapid epimerization of stereogenic

carbanions, except when R1 = OR
(Still, JACS 1978, 100, 1481 & JACS 1980, 102, 1201)

sp does not easily invert

R C C
sp

stability:
3o < 2o < 1o < allylic, benzylic
sp3 < sp2 < sp
[note: these trends are exactly opposite those of carbocations]
R3SiC

<

R2NC

<

<<

RSC

O
R C C
(enolate)

generation of carbanions
1) reduction of bonds
R X

Mo

R M

120

M X

<

O
R S C
O

651.06
ex:
Mgo

R Br

R MgBr

Et2 O

Grignard Reaction
Bao

Cl

BaCl

Yamamoto, JACS 1994, 117, 6130

other bonds (besides R-X) can be reduced:

"lithium naphthalide" - single electron reductant

O

Li

SPh

Li

Accts. Chem. Res. 1989, 22, 152

H
R
O

SPh

Li

H
O

Li
O

THF, - 78

axial

H
O

Li
O

-780 to -20o

(stable at -78o )

(>99:1)
-inverse
anomeric effect

Rychnovsky, JACS 1992, 57, 4336

2) Metallation (deprotonation)
-very basic reagents can deprotonate C-H
-like any acid / base chemistry, its an equilibrium dictated by pKa
so, we use n-BuLi, s-BuLi, t-BuLi, PhLi
OMe

ex:

tBuLi
THF, 0 o

Why that product?

OMe
Li

JOC 1979, 44, 2004

sp2 C next to O most acidic (pKa 30) Keq 10(50-30) 1020

121

651.06
also:
KOtBu

Li

z isomer is favored

BuLi
THF
"LICKOR"
"Schlosser base"

Schlosser, JACS 1978, 100, 3258

structure of LICKOR base:

Venturello, Tetrahedron 1996, 52, 7053

note that many hydrocarbons cant be easily deprotonated due to kinetics

another special case:

O

NEt 2

Et 2N

n-BuLi

Li

TMEDA
THF, -78o

ortho metallation (stabilized by O-Li

bond)

also:
Li
O

OH

Li

s-BuLi
THF

OMe

JOC 1977, 42, 1823

O
s-BuLi

OMe
Li

JOC 1979, 44, 4463

122

651.06
3) Transmetallation

R1 M1

R2 M2

R1 M2

R2 M1

equilibrium favors putting more electropositive M on more acidic R

ZnBr

tBuLi

Li

tBuZnBr

ex:
corrollary:
MgBr2

R Li

ZnBr 2

R Li

CeCl3

R Li

CuI

R Li

R MgBr

LiBr

R ZnBr

LiBr

R CeCl2

LiCl

(very synthetically useful)

LiI

(very synthetically useful)

R2 CuLi

(consider Br as R2)

this follows electropositivity: Li, Na, K > MgII, CaII > ZnII > CuI > PdII
(ionic)

(covalent)

hard

soft

related exchange reactions:

R SnBu 3

BuLi

R Li

stable, chromatographable

Bu4Sn

works if R is more acidic than butane (pKa 46)

also, metal - halogen exchange:

R1 X

R2 Li

R1 Li
-110o to

X = Br, I

R2 X

-30 o

-equilibrium governed by basicity of R1, R2

(favors less basic R-Li)

-very fast reaction! (competes with proton transfer)

123

651.06
mechanism:
R1 X

(+ e- )

R2 Li

R1 X

R2

-X
(+ e -)
R1Li

R2 X

R1

R1 R2

R2

-sequential single electron transfers

evidence is the formation of R1-R2 as a minor side-product (so-called Wurtz coupling)
this can be made irreversible:
H
R I

tBuLi (2eq)

Li

R Li

RLi

elimination

Seebach, TL 1976, 4839

Characteristic Reactions
1) acid / base chemistry
2) transmetallation / metal-halogen exchange
3) nucleophilic addition

R M

+
R'

O
R

(works best when Y = H, OR, NR2, X;

124

Y
R'

R = 1o, allylic, sp2, sp)

LiI

651.06
4) nucleophilic substitution (uncommon)

R M

R'

R R'

M X

-note that this is the Wurtz Coupling, a side reaction of Li / X exchange

most common when M = CuI,, but probably isnt SN1 or SN2

Ylides - a special class of carbanions

H
R 2C YRn

base
R 2C YR2

When a carbon - to a positively charged heteroatom is deprotonated, it forms an ylide

(yl = ; ide =

-very stable carbanions

ex:

R 2C PR3 , R 2C SR2 , R 2C NR3

(less stable)

(note that R 2C SO2 R , R 2C PO3 R , R 2C NO2 can be viewed as ylides)

Enolates - another special class of carbanions

O

base

Abstraction of acidic -proton produces resonance-stabilized carbanion => very useful

125

651.06

Free Radicals - Species containing unpaired electron(s)

hybridization of carbon varies between sp3& sp2 depending on the substituents

(

CH3

is planar ) => 7 valence electrons (electron deficient like carbocations)

like carbanions, free radicals can be chiral, but invert too rapidly
stability:
look at C-H bond strengths (first handout)
1o < 2o < 3o < benzylic, allyl, acyl (similar to cation)
sp < sp2 < sp3
EWG CR2

>

O
EWG = OR, NR2 , SO2R, CN, CY

CR3

Why do electron - withdrawing substituents stabilize -radicals?

through resonance, primarily:

RO

R'

RO

R'

very stable radicals:

Ph3C

N
O
O
stable & isolable

126

651.06
unstable radicals:
RO

R2N

(note that RS

,
is quite stable)

Methods of generation:
1) homolytic bond cleavages

O
R

O
O O

! or h"
R

- CO2

2R

CN
N N

! or h"
2
( - N2 )

CN

CN

(AIBN)

O
N X

h!

N
O

(X = I, Br, Cl)

127

651.06
2) photochemical excitation of bonds
O
R

h#
R'

! = 300nm
(n
"*)

diradical - behaves much like 2

isolated radicals

R'

Characteristic reactions:
1) atom transfer

Y R'

R Y

R'

equilibrium process favoring stable radical

ex:
Br

Bu3SnH, AIBN (5%)

,

mechanism:
very weak bond

CN
N N
CN

!
( - N2 )

NC

H SnBu3

H atom
transfer

Br
SnBu3

- NC
Br transfer
- Bu 3Sn Br

Bu 3Sn H
H atom
transfer

typically, H & X transfers are observed

(note: also a method of generating new radicals)

128

v. stable
bond

651.06
2) Addition to systems

the most common variant of this reaction is intramolecular:

CH3

Bu3SnH, AIBN (cat.)

PhH, h!

Br

mechanism:

SnBu3

CH2

5 - exo trig

Br

Bu3SnH

radical cyclization:
review:

Beckwith, Tetrahedron 1981, 37, 3073

Curran, Synthesis 1988, 417 & 489

- system can also be

R C N

radicals most easily detected by electron spin resonance (ESR)

- they appear as doublets

129

H SnBu3

CH3

651.06

Radical Anions & Cations

These species consist of neutral molecules that have gained (R. A.) or lost (R.C.) a single
electron.
Li
NH3 (l)

Li
lithium naphthalide

"dissolving metal"
reduction

ex:

What is meant by the structure?

etc.

-an extra electron is delocalized throughout the system

(unlike free radicals, no addition/loss of atoms during formation)
MO description:
!"

!"

e-

!3

!3

extra electron is placed in antibonding MO

likewise we can place an extra electron in * orbital:

O

SPh

Li

SPh

- PhS

very common example:

O

Nao

Na

sodium benzophenone ketyl (blue-purple)

130

651.06
radical cations are somewhat more rare; most commonly encountered when single
electron oxidants are used (also in mass spectroscopy)
ex:
CeIV

OMe
R O

CH3 CN-H2O

OMe
R O

para-methoxybenzyl (PMB) group

OR

OR

OR
etc.

MO description
!1"

!1"

e-

!2

!2

vacant bonding orbital (hole in 2)

Radical cations also arise in the oxidations produced by DDQ

O
NC
O

NC

Cl
O

Cl
(- e- )

-H

NC

Cl

NC

Cl
O

very e- deficient

(- e- )
OH
NC

Cl

NC

Cl
OH

131

-H

651.06
radical ions can also be distonic (Kenttamaa)
ex:
O

O
vs.

-differing stabilities, reactivities

(these species are very important in mass spectrometry experiments)

Carbenes - neutral molecules lacking on octet

R1
C
R2

divalent carbon with two non-bonded electrons

VERY reactive & unstable

two different spin states:

!2

!2
vs.

!1

!1

singlet (J = 0)

triplet (J = 1)

at first approximation, we can consider them as:

R1
C
R2

R1
C
R2

triplet

singlet

-behaves as isolated radicals

-behaves as zwitterion

sp3

sp2

R1

R1

R2

R2

132

651.06
structure:
much debate on structure of methylene (CH2)

C
H

oH

136
triplet

H
103 o
singlet

triplet - Wasserman, JACS 1970, 92, 7491

singlet - Herzberg, Nature 1959, 183, 1801

- same bent structure holds for most other carbenes

stability:
methylene (CH2) is a ground state triplet (by 8 - 10 kcal/mol)
-normally, carbenes are generated as singlets

carbenes are stabilized by resonance:

H2C

<

O
HC COR

<

<

HC

X C H

<

X C X

(X = Cl, Br)
a very stable carbene has been reported:

Arduengo, JACS 1991, 113, 361

133

651.06

Methods of Generation

1) - elimination

H
R

base

X
R

X
R

slow

C
R

ex:
HCCl3

KOH

CCl 2

H2O
35o

(dichlorocarbene)

also:
HCCl3

MeLi
THF
-78o

CHCl2

-78o to 25o

CHCl

(chlorocarbene)

In many cases, one can get a carbenoid instead:

CH2 I2

Zn o

2
Zn(CH2 I)2

Zn(CH2 I)2

stable to - elimination but behaves like a carbene

Simmons - Smith reagent

2) decomposition of diazo compounds

C N2

R1

h! or "
- N2

R C

R1

( gives singlet, h gives excited state)

134

651.06
mechanism:
R

C N N

- N2

C N N

R1

R1

R C

! - elim.

R1

also works with diazirines:

R 2C

h! or "

N
N

R C

- N2

most important to synthetic chemists is the metal-catalyzed decomposition:

C N2

Rh2(OAc)4

R1

"R 2C MLn"

- N2

stable, but reacts like carbene

see, e.g.: Doyle, JACS 1996, 118, 8837

Characteristic Reactions
1) Cyclopropanation

R C

R1

R 2C

singlet and triplet behave differently

:CH2

one isomer

singlet

:CH2

triplet

135

mixture

651.06

singlet reacts in concerted fashion (no intermediate)

H
can rotate

triplet reacts via diradical intermediate:

can invert

Skell, JACS 1956, 78, 4496

more commonly:

N2CHCO2Et

CO2Et

Rh2(OAc)4

Zn-Cu, CH2I2

"Simmons-Smith reaction"

[via Zn(CH2I)2]

Cl

CHCl3, KOH
25

Cl

[via CCl2]

2) C-H insertion
H
H

:CH2

how? Maybe via 3-center, 2-electron transition state

136

CH3
H

651.06
for preparative purposes:
O

O
Rh2(OAc)4

O
N2

H O

THF
H

Doyle in Comprehensive Organometallic Chemistry II, (1995), Vol. 2, Ch. 5.2

(very powerful transformation stereoselective functionalization of methylene group)
this can also be intramolecular:

C-H

KOH
Br

Br

- 30o

>

25o

insertion
H

Doering, Tetrahedron 1960, 11, 266

3) Rearrangements (like carbocations)

1,2 shift
Schechter, JACS 1960, 82, 1002
also:
O
R
N2

or Rh2 (OAc)4

h!, "

C
R
(ketene)

(- N 2)

this is known as the Wolff rearrangement (JACS 1961, 83, 492)

when the ketene is trapped by an alcohol, its the Arndt - Eisnert rxn

137

ROH
R

CO2R

651.06
The nitrogen equivalent (nitrenes) are also known:

N3

h! or "

very reactive
they behave similarly to carbenes, but are less stable and more reactive

138