Carbenes

Carey & Sundberg, Part B, Chapter 10, 614-650.

H
H
H
H
Carbene Electronic Structure
Triplet (two unpaired e
-
)
Singlet (all e
-
paired)
p

p
Often has radical-like character
Capale of both electrophilic and
nucleophilic behavior
1.078
133.8
Nitrene Electronic Structure
R N
Singlet (all e
-
paired)
empty
filled
filled
R N
H
empty
filled
Nitrenium ion
H
Carbenes: Introduction
Carbenes: An Introduction
p
Energy

Due to electron repulsion, there is an energy cost in pairing both electrons in the orbital.
If a small energy difference between the and p orbitals exists, the electrons will
remain unpaired (triplet). If a large gap exists between the and p orbitals the
electrons will pair in the orbital (singlet).
singlet
810 kcal/mol
T
1
S
1
Carbene Configuration: Triplet vs. Singlet
p
triplet
The History of the Singlet-Triplet Gap
Method
HCH Angle
ST Splitting
kcal/mol
Author Year
Qual. 90-100
Muliken
1932
Grnd State
singlet
Thermochem 180 small
Walsh
1947
triplet
160 30
Gallup
1957
triplet
Qual. QM
138 >33
Harrison
1969
triplet
Ab initio
89
Hase
1971
triplet
Kinetics
19
Pople
1971
triplet
SCF 132
8.7 Dewar 1974 triplet MINDO 134
19.5 Lineberger 1976 triplet Expt 138
19.7 Schaeffer 1976 triplet An Initio
8.1 Zare 1978 triplet Expt
8.5 Haydon 1982 triplet Expt
Carbenes: Introduction
Carbenes: Structure
The p orbital of carbenes substituted with p-donor atoms (N, O, halogen) is raised high
enough in energy to make the pairing of the electrons in the orbital energetically
favorable. As a result, these carbenes are often in the singlet state.
C
Cl
Cl
Heteroatom-Substituted Carbenes: Singlets
p
triplet
carbene

Energy
donor p
orbital
-donor
heteroatom
Heteroatom-
substituted
carbene
Examples: Singlet
C
H
C
6
H
5
Singlet
Carbene Structure
Carbenes: Structure and Generation
C
X
X
X
H
C
Cl
Cl
C C O
R
R
Alkyl Halides
heat or h
R
2
C
+
Ketenes
R
1
R
2
N N
R
1
R
2
N N
R
1
C
R
2
Diazo compounds
h or heat
+ N
2
N
N
R
2
R
1
diazirines
h or heat
CO
OR
X = Cl, Br, I
Carbene Structure and Formation
Carbenes: Structure and Generation
R
1
R
2
N N
Rh
Rh
O
O
Me
Rh
Rh
O
O
Me
R
1
R
2
N
N
Rh
Rh
O
O
Me
R
1
R
2
Rh
Rh
O
O
Me
R
1
R
2
Carbenoids by Metal-catalyzed decomposition
carbenoid
(ligands omitted for
clarity)
Rh
2
(OAc)
4
-N
2
Doyle Chem Rev. 1988, 86, 919.
Rh
2
(OAc)
4
R
1
R
2
N N
R
1
R
2
Rh
II
A rhodium carbenoid
Cu
I
X
R
1
R
2
N N
R
1
R
2
Cu
I
A copper carbenoid
Rh
O
O
O
O
O
O
O
Me
Me
Me
Me
Rh
O
Rh
2
(OAc)
4
=
Carbene Structure and Formation
Carbenes: Structure and Generation
N
N
H
N
N
N
N
N
N
N
N
NaH, THF
cat. tBuOK
"Stable Carbenes"
Arduengo et al. J. Am. Chem. Soc. 1991, 113, 361; 1992, 114, 5530.
(89%)
Arduengo et al. J. Am. Chem. Soc. 1994, 116, 6812, Neutron diffraction study:
Arduengo argues that these resonance structures are not players based on electron
distribution from neutron diffraction.
These are nucleophilic carbenes which display high stability.
S
N
Me Me
Au
F
F
F
F
F
H. G. Raubenheimer
Chem. Comm. 1990, 1722.
Xray Structure
Regitz, M. Angew. Chem. Int. Ed. Engl. 1991, 30, 674
Cl
Carbene Structure and Formation
Carbenes: Structure and Generation
+
R
R
R
R
R
R H
2
C
R
R
H
2
C
R
R
R
R H
2
C
R
R
Cyclopropanation
H
2
C
R
R
+
1
R
R
3
Triplet carbenes add non-stereospecifically
Skell and Woodworth JACS, 1956, 78, 4496.
Singlet carbenes add to olefins stereospecifically;
ISC
ISC
CH
2
CH
2
Carbene Structure and Formation
Carbenoids: Cyclopropanation
McKervey et al. JCS PTI, 1991, 2565.
N
2
CO
2
Me
Me
AcO Me
O
N
2
Me
AcO
Me O
O
Me
Me
OTBS
H
Me
Me
H
O
H
H
O
Buchner Reaction
cat.
confertin
(84%)
CO
2
Me
Rh
2
(OAc)
4
CO
2
Me
Cyclopropanation
Carbenoids: Other Reactions
OMe
OMe
O
2
N
OMe
Me
O
N
2
OMe
OMe
O
2
N
CO
2
H
OMe
Me
Wolff Rearrangement
Evans et al. J. Org. Chem. 1993, 58, 471. (+) Macbecin
retention
AgOBz
H
2
O
Rearrangement
Carbenes: Rearrangements
Other Rearrangements
Schecter, J. Am. Chem. Soc. 1971, 93, 5940.
O
H
O
H
O
O
N
2
O
O
N
2
N
OTBS
TIPS
Teoc
Br
Br
O
O
Ph
Ph
N
OTBS
TIPS
Sammes, Chem. Comm. 1975, 328.
Teoc
150C
O
O
Vinylidenes
Ph
Ph
Corey-Fuchs:
Danishefsky et al.
J. Am. Chem. Soc. 1996, 118, 9509.
2 eq. BuLi
-78C
(81%)
(71%)
(92%)
O
H
O
H

200C
O
O
Rearrangement
Carbenes: Rearrangements
CH Insertions
Me
O
N
2
CO
2
Me
O
CO
2
Me
Me
N
CO
2
Me
N
2
O
O
N
CO
2
Me
O
O
H
(83%)
(75%)
Stork Tetrahedron Lett. 1988, 29, 2283.
Sulikowski, J. Org. Chem. 1995, 60, 2326.
H H
N
H
O
Me
H
HO
O
CO
2
PNB
N
H
O
Me
H
HO
O
CO
2
PNB
N
H
O
Me
H
HO
S
CO
2
NH
3
thienamycin
Salzmann, JACS, 1980, 102, 6163.
NH Insertions
NH
H
O
Me
H
HO
CO
2
PNB
O
N
2
Rh
2
(OAc)
4
CuOTf
Rh
2
(OAc)
4
Rearrangement
Carbenes: Rearrangements
Me
Me O
N
2
Me
O
Me
Wolff-[2+2]
h
J. Org. Chem. 1980, 45, 2708.
(74%)
Me
Me C
O
H
+
Rearrangement
Carbenes: Reaction with Heteroatoms
R
R R R
O
R O R
R R
Generally, the carbene precursor of choice is a diazoalkane or, more frequently,
an -diazocarbonyl reagent. These can be decomposed via thermolysis or
photolysis. However, the most common method involves catalytic amounts of
transition metals, such as copper or rhodium.
Ylide Formation by the Interaction of Carbeneoids
with Carbonyl Lone Pairs

R O R
R R
R O R
R R
X Y
R O R
R
R
X Y
Dipolar Cycloaddition
Rearrangement
Carbonyl Ylids: Dipolar Cycloaddition
O
CHN
2
O
O
O
R
R
O NPh
R
O
O
O
H
H
O
CO
2
CH
3
CO
2
CH
3
R
O
O
N
CO
2
Et
R
O
O
O
R
N C CO
2
Et
R
O
NPh
H
O
O
Tandem Intramolecular CyclizationIntermolecular Cycloaddition
RCHO
Rh
2
(OAc)
4
CO
2
CH
3
CO
2
CH
3
Ylide Dipolar Cycloadditions
Carbonyl Ylids: Dipolar Cycloaddition
Reactions of Diazoimides: [3+2] addition
74%
Et
3
SiH / BF
3
Et
2
O
CH
2
Cl
2
68%
Maier, M. E.; Evertz, K. Tetrahedron Lett. 1988, 29, 1677-1680.
O
N
O Bn
H
CH
3
N
Me
H
Me
OH
H
O
Bn
O
N Me
O O O
N
2
Bn
O
N
O Bn
COMe
H
Me
Me
PhCH
3
, 110 C
O
N
O Bn
COMe
Padwa et. al. Tetrahedron Lett. 1992, 33, 4731-4734.
"high yield"
Rh
2
(OAc)
4
PhH, reflux
N Me
O
O O
N
2
N
O
Me
H
H
O
O
N
O
N
Me
O O
N
2
N
N
O Me
O
O
H
H
H
88%
Me
Me
O
Rh
2
(OAc)
4
N
2
Ylide Dipolar Cycloadditions
Intermolecular addition to -unsaturated carbonyls
Spencer Tetrahedron Lett. 1967, 1865-1867.
2-methoxymethylenecholestanone-3
29%
CuSO
4
160 C
The Synthesis of Furans
OMe
O
OMe
O
O
EtO
2
C
EtO
2
C
Et
O CHN
2
O
Cu(acac)
2
89%
CO
2
CH
3
O
O
O
O
N
2
CH
3
O
CO
2
CH
3
O
O
O
CH
3
O
HO
Can you propose a rational mechanism for this transformation?
Carbonyl Ylids: Dipolar Cycloaddition
Ylide Dipolar Cycloadditions
Intermolecular addition to -unsaturated carbonyls
Spencer Tetrahedron Lett. 1967, 1865-1867.
2-methoxymethylenecholestanone-3
29%
CuSO
4
160 C
The Synthesis of Furans
OMe
O
OMe
O
O
EtO
2
C
EtO
2
C
Et
O CHN
2
O
Cu(acac)
2
Hildebrandt, Tetrahedron Lett. 1988, 29, 2045-2046.
89%
CO
2
CH
3
O
O
O
O
N
2
CH
3
O
CO
2
CH
3
O
O
O
CH
3
O
HO
Can you propose a rational mechanism for this transformation?
O
O
O
O
CO
2
CH
3
CH
3
O
CO
2
CH
3
O
O
O
CH
3
O
O
Carbonyl Ylids: Dipolar Cycloaddition
Ylide Dipolar Cycloadditions
Stevens Rearrangement ([1,2] alkyl shift)
R
2
N N
2
R
1
O
Rh
2
(OAc)
4
N
O
R
1
R
2
N
O
R
2
R
1
West, JACS 1993 1177
Ylide Rearrangement
Vedejs, JACS 1989, 111, 8430
Methynolide has been synthesized by Vedejs
using this ring-expansion methodology
72%
72%
50%
Ring expansion reactions
S
N
2
CO
2
Et
S
CO
2
Et
S
CO
2
Et
S S
Et O
Me
O
TfO CO
2
Et
S
EtO
2
C
Me
Me
OH
HO
Me
O
Cu(I)
DBU
KOt-Bu
Ring Expansion