REACTIVE INTERMEDIATES: CARBENES
CARBENES: Reactive 6-electron divalent carbon fragments R2C:
R
2
sp
R
ca. 32-42 kJ mol-1
C
R
R
C
Triplet
Singlet
RCR Å 130-150°
RCR Å 100-110°
H2C: = carbene = methylene = methylidene
R
H
N
= adamant-1-yl
R =
H
N
R
Isolable singlet carbene - Crystallographically
characterised.
(Wanzlick et al. 1970)
2p
C
sp2
Stable triplet carbene - half-life ca. 1 week in inert atmosphere.
(Iwamoto et al., 2004)
R2C .... M
Kinetically reactive transition metal 'carbenoid' of
uncertain structure. Involved in catalytic carbene
transfer. Structures generally unknown.
CH3
Br(CO)4Cr C
OCH3
Kinetically unreactive structurally characterised metal
carbene complex. Used as a stoichiometric (i.e. noncatalytic) carbene transfer reagent.
Relationship of carbenes to other reactive fragments:
X
C
_
- X–
C:
C:
R+
Carbanion
+
C R
Carbocation
Loss of a leaving group from carbanionic carbon is one synthetic
pathway to carbenes.
The formal carbene-carbocation relationship
suggests that carbenes can also act as nucleophiles.
GENERATION OF CARBENES:
(1) -ELIMINATION OF HX OR X2 FROM AN ORGANIC HALIDE
X
- X, -Y
C
C:
Y
How do we know that a carbene is formed?
Base H2
C
CH3
Base,
- HCl
CH3
H2
C
Base
- HCl
CH3
C
H2
CH3
CH2Cl
C
H2
_
CHCl
- Cl-
Base, - HCl
-Elimination
CH3
H2
C
C
H2
CH:
-Elimination
H2
C
CH3
H+
H2
C
H2
C
C
H
C
H2
CH2
CD2Cl
Rearrangement
Base, - DCl
-Elimination
-Elimination
C
H
CD2
CH3
H2
C
C
H2
CD:
Rearrangement
CH3
H2
C
C
H
CHD
H3C
H2
C
C
H2
CH2Cl
C6H5Na
H3C
H3C
C
H
C
H
CH2
94% a-Elimination
6% b-Elimination
NaOCH3
H2
C
H2
C
CH2
10% a-Elimination
90% b-Elimination
H 3C
H2
C
C
H2
CH2Cl
Base, - HCl
-Elimination
H H
C  CH:
H 3C  C
H2
CH3
Insertion of carbene into
-CH bond.
Geuther (1862), Hine (1950):
HCCl3 + 4 NaOH
NaHCO2 + 3 NaCl + 2 H2O
NaOH + HCCl3
H2O + NaCCl3
NaCl + :CCl2
NaCCl3
RCH CHR
HCCl3
NaOH
RCH CHR
CCl2
Carbene generation via lithium-halogen exchange:
RLi + R1Br
RX + R1Li
The reaction of an organolithium compound with an organic halide is a
general one and proceeds - as you might expect - in the direction of
combining lithium with the most carbanion-stabilising organic group.
Starting with carbon tetrabromide it is a convenient route to
dibromocarbene:
- LiBr
BuBr + LiCBr3
CBr4 + BuLi
:CBr2
-elimination
Carbene generation via -elimination under mild non-basic conditions:
Thermolysis of sodium trichloroacetate:
O
Cl3C C

O- Na+
CO2 + NaCCl3
- NaCl
:CCl2
The Simmons-Smith reaction:
OH
OH
CH2I2
Zn/Cu
CH2I2 + Zn
CH2
:CH2 + ZnI2
Although the active carbene transfer reagent is thought to be the zinc
carbenoid [I2Zn...CH2] it seems that the organozinc reagents ICH2ZnI
and/or IZnCH2ZnI are formed first. Note the stereospecificity of the
reaction.
(2) -ELIMINATION OF N2 FROM DIAZO-COMPOUNDS
R1
+ _
C N N
R1
 or h
or [M]
C:
+ N2
(i) p-TolSO2NHNH2, H+
(ii) Na, HOCH2CH2OH
RHC:
R2
R2
The Bamford-Stevens Reaction:
R-CHO
(p-Tol = 4-CH3C6H5; HOCH2CH2OH = ethylene glycol)
R-CHO + H2N-NH-SO2Tol-p
H+
RCH=N-NH-SO2Tol-p + H2O
p-Toluenesulphonylhydrazone
RCH=N-NH-SO 2Tol-p
NaOR
- H+
–
RCH=N–N–SO 2Tol-p
Acidic H, activated
by -sulphonyl group.
_
+
RCH=N=N + [SO 2Tol-p]–
p-Toluene
Diazoalkane
sulphinate
anion
_ +
RCH–N N
:
–
RCH=N—N—SO 2Tol-p
_
+
RCH=N=N
_ +
RCH–N N

RHC: + N2
-Carbonyl diazo-compounds - Important precursors of -carbonyl
carbenes:
+ _
xs. CH2=N=N
R-COCl
R-COCl +
(Diazomethane)
+ _
R-CO-CH=N=N
+ _
CH2=N=N
_
+
CH2-NN
_
+
CH2-NN
+
R-CO-CH2-NN + Cl+ _
R-CO-CH=N=N + H+
+
R-CO-CH–NN
H
_ +
CH2-NN
+ HCl
CH3Cl + N2
H
R
H
C + _
C
N
N
O
R
C +
C
N
N
_
O
-Carbonyl
diazo-compound
Diazonium
enolate
H
R
C +
C
N
N
_
O
Diazonium
enolate
H
, [Rh]
- N2
R
C
C
O
-Carbonyl carbene
REACTIONS OF CARBENES:
Carbenes are highly electron-deficient since the carbene carbon has
only 6 electrons in the valence shell. Hence carbenes are highly
electrophilic species. This is reflected in the three major classes of
carbene reactions.
(1) Carbene insertions
(2) Carbene additions
(3) Carbene rearrangements
Insertion into single bonds:
R1
C: +
R2
R1
A
C
B
A
B
R2
Addition to multiple bonds - formation of 3-membered rings:
R1
C: +
R2
R1
A
C
B
A
B
R2
Rearrangement (intramolecular insertion into a single bond):
R
R
C C:
C C
R1
R
C C
R1
A
A
B C
R1
B C
R1
R1
CARBENE INSERTIONS INTO E-H BONDS:
R1
C: +
R2
R1
H
C
E
H
E
R2
E = C, Si, O, S, Se, F, Cl, Br
Simple carbenes are highly reactive and show little or no selectivity in
C-H insertion:
_
+
CH2=N=N + CH3CH2CH(CH3)2

Statistical distribution of
insertion products
Carbonyl carbenes are more selective:
EtOCOCH=N2

3° CH > 2° CH > 1° CH insertion
[Rh]
Intramolecular insertions also show enhanced selectivity:
O
NNHTs
Base, 
2
3
- H2O
1,5-insertion
66%
:
TsNHNH2
1
5
4
1,3-insertion 1,2-insertion
10%
(Rearrangement)
22%
N.B. Ts = p-TolSO2-
Carbene C-H insertion in a natural product synthesis:
H3C H
O
Ar
N2
CO2CH3
O
O
[Rh]
Ar
H
CO2CH3
Ar
CH3
CH3
CH3
CH3
-Cuparenone
Carbene insertion into an O-H bond:
O
CH3
C
O
[Rh]
CHN2
+ ROH
CH3
C
CH2OR
+ N2
Carbene insertion into an N-H bond - Merck industrial synthesis of a lactam antibiotic:
O
NH
O
N2 CO2R
[Rh]
C 6 H6
O
N
O
CO2R
Carbapenam
CARBENE ADDITION REACTIONS:
Cyclopropane synthesis:
C6 H 5
CHCl3
KOBut
C6H5
Cl
Cl
1 Eq. R3SnH
[In•]
C6H5
Cl
H
1 Eq. R3SnH
[In•]
C6H5
H
H
Metal-halogen
exchange
C6H5CHBr2 + n-BuLi
Li
C6H5CH
Br
-Elimination
- LiBr
C6H5
H
Cyclohexene
C6H5
C:
H
The stereochemistry of carbene addition to alkenes can be used as a test
of whether the carbene is reacting via the singlet or the triplet spin state:
Alkenes react with singlet carbene in a concerted fashion - alkene
stereochemistry is preserved in the cyclopropane product:
LUMO
HOMO
HOMO
LUMO
X
R
R
Y
:CXY
R
R
Note that the parallel orientation of the planes of the interacting singlet
carbene and alkene are not what you would expect from the geometry
of the two fragments in the cyclopropane product.
LUMO
HOMO
HOMO
LUMO
If the fragments approach with what would intuitively be the 'correct'
orientation no net bonding will result.
Alkenes react with triplet (i.e. diradical) carbene in a stepwise fashion the alkene stereochemistry is lost in the cyclopropane product:
RAPID
X
Y
X
H
R
Y
R
H
X
Y
R
H
H
H
H
R
R
R
Spin-flip: SLOW
X
X
Y
Y
R
H
H
R
X
H
R
H
H
X
Y
R
H
R
R
H
R
Y
H
R
Carbene additions to arenes: 6
trienes:
7 ring-expansion to yield cyclohepta-
[Rh]
+ N2 CHCO2Et
CHCO2Et
Norcaradiene
Electrocyclic
rearrangement
CHCO2Et
Carbene additions to pyrrole - 5
6 ring-expansion to yield pyridines:
Cl
CHCl3/OH-
Cl
N
_
N
H
OH–
:CCl 2
N
_
CHCl3/OH-
- Cl
Cl
-
N
CARBENE REARRANGEMENTS:
Mechanism: 1,2 migration of hydride or a carbanion:
R
R1
C
R1
R3
C
R3
C
C
R2
R2
R
Migratory aptitude: R = H >> aryl > alkyl
Arndt-Eistert Reaction - homologisation of carboxylic acid derivatives:
RCO2H
SOCl2
xs. CH2N2
RCOCl
RCOCHN2
h,  or [M]
RCH2COZ
HZ
Z = OH, OR, NR2 etc.
H
R
R
C C O
C:
C
H
O
Wolff Rearrangement
of an acylcarbene to a
ketene.
H2O
R
R
C C O
H
+
OH2
C C
H
O–
OH
R
C C
H
OH
R
OH
C C
H H
O