Transcript Carbenes Carey & Sundberg , Chapter 10, 614-650.

Carbenes
Carey & Sundberg, Part B, Chapter 10, 614-650.
Carbenes: Introduction
Carbene Electronic Structure
1.078 Å
p
H
p
H

133.8Þ
H

H
Triplet (two unpaired e-)
Singlet (all e- paired)
Capale of both electrophilic and
nucleophilic behavior
Often has radical-like character
Nitrene Electronic Structure
empty
empty
filled
R
N
H
H
R
N
filled
filled
Singlet (all e- paired)
Nitrenium ion
Carbenes:
Introduction
Carbenes: An Introduction
Carbene Configuration: Triplet vs. Singlet
p

S1
E
n
e
rg
y
8–10 kcal/mol
T1
singlet

p
triplet
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).
The History of the Singlet-Triplet Gap
Year
Method
1932
Qual.
Author
HCH Angle Grnd State
Muliken
90-100°
singlet
S–T Splitting
kcal/mol
––
1947
Thermochem
Walsh
180°
triplet
1957
Qual. QM
Gallup
160°
triplet
30
1969
Ab initio
Harrison
138°
triplet
>33
1971
Kinetics
Hase
––
triplet
8–9
1971
SCF
Pople
132°
triplet
19
1974
MINDO
Dewar
134°
triplet
8.7
1976
Expt
Lineberger
138°
triplet
19.5
1976
An Initio
Schaeffer
–––
triplet
19.7
1978
Expt
Zare
–––
triplet
8.1
1982
Expt
Haydon
–––
triplet
8.5
small
Carbene Structure
Carbenes: Structure
Heteroatom-Substituted Carbenes: Singlets
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.
donor p
orbital
p
Energy

triplet
carbene
Heteroatomsubstituted
carbene
Cl
Examples:
H
C
Cl
-donor
heteroatom
Singlet
C
C6H5
Singlet
Carbenes:
Structure and
Generation
Carbene
Structure
and
Formation
Alkyl Halides
X
C
X
Cl
OR
H
C
Cl
X
X = Cl, Br, I
Ketenes
R
C
C
heat or h
O
R2C
+
CO
R
Diazo compounds
R1
R1
N N
R2
N N
h or heat
R2
diazirines
R1
N
R2
N
h or heat
R1
C + N2
R2
Structureand
and Generation
Carbene Carbenes:
Structure
Formation
Carbenoids by Metal-catalyzed decomposition
R1
R1
Rh2(OAc)4
N
N
R2
RhII
A rhodium carbenoid
CuI
A copper carbenoid
R2
R1
R1
CuIX
N
N
R2
R2
Me
Me
Me
O
Rh2(OAc)4 =
O
O
Rh
O
O
O
Rh
N
O
O
O
O
O
R1
Rh2(OAc)4
(ligands omitted for
clarity)
N
R2
Rh
R2
Rh
Me
O
R2
Rh
O
Rh
-N2
N
N
Me
R1
Me
Rh
R1
O
Rh
Me
Me
carbenoid
O
R1
R2
Doyle Chem Rev. 1988, 86, 919.
Rh
O
Rh
Carbenes:
Structure andand
Generation
Carbene
Structure
Formation
Cl
N
"Stable Carbenes"
NaH, THF
N
cat. tBuOK
N
H
N
(89%)
N
N
N
N
N
N
Arduengo argues that these resonance structures are not players based on electron
distribution from neutron diffraction.
These are nucleophilic carbenes which display high stability.
Me
Me
F
N
S
F
X–ray Structure
Au
F
F
H. G. Raubenheimer
Chem. Comm. 1990, 1722.
F
Regitz, M. Angew. Chem. Int. Ed. Engl. 1991, 30, 674
Arduengo et al. J. Am. Chem. Soc. 1991, 113, 361; 1992, 114, 5530.
Arduengo et al. J. Am. Chem. Soc. 1994, 116, 6812, Neutron diffraction study:
Carbene Structure and Formation
Carbenes: Structure and Generation
Cyclopropanation
1 CH
2
R
R
Singlet carbenes add to olefins stereospecifically;
+
R
R
R
R
3 CH
2
R
ISC
+
Triplet carbenes add non-stereospecifically
H2 C
R
R
R
H2C
R
R
H2C
ISC
R
R
R
R
H2C
Skell and Woodworth JACS, 1956, 78, 4496.
R
R
Cyclopropanation
Carbenoids: Cyclopropanation
Buchner Reaction
CO2Me
cat.
CO2Me
N2
CO2Me
Me
Me
O
Rh2(OAc)4
(84%)
AcO
Me
Me
N2
AcO
Me O
Me
H
H
H
O
O
Me OTBS
O
McKervey et al. JCS PTI, 1991, 2565.
H
Me
confertin
Rearrangement
Carbenoids: Other Reactions
Wolff Rearrangement
OMe OMe O
OMe OMe
N2
O2N
Me
O2N
CO2H
AgOBz
Me
H2O
OMe
Evans et al. J. Org. Chem. 1993, 58, 471.
retention
OMe
(+) Macbecin
Rearrangement
Carbenes: Rearrangements
Other Rearrangements
150ÞC
H
O
H
O
(71%)
N2
H
H
O
O

Schecter, J. Am. Chem. Soc. 1971, 93, 5940.
N2
O
200ÞC
O
O
(92%)
O
O
O
Sammes, Chem. Comm. 1975, 328.
Vinylidenes
Corey-Fuchs:
Danishefsky et al.
J. Am. Chem. Soc. 1996, 118, 9509.
TIPS
Teoc
TIPS
O
N
O
Br
OTBS
Br
Ph
Teoc
N
Ph 2 eq. BuLi
O
O
-78ÞC
(81%)
OTBS
Ph
Ph
Rearrangement
Carbenes: Rearrangements
N2
C–H Insertions
H
O
Rh2(OAc)4
O
H
CO2Me
CO2Me
Me
Me
CO2Me
CuOTf
H
O
N
N2
Me
O
(75%)
O
H H
HO
CO2PNB
Rh2(OAc)4
H H
Me
N–H O
N
O
O
HO
O
CO2PNB
Salzmann, JACS, 1980, 102, 6163.
H H
Me
N
O
Sulikowski, J. Org. Chem. 1995, 60, 2326.
N
O
N–H Insertions
(83%)
CO2Me
N2
HO
Stork Tetrahedron Lett. 1988, 29, 2283.
S
CO2
thienamycin
NH3
HO
H H
Me
N
O
O
CO2PNB
Rearrangement
Carbenes: Rearrangements
N2
Wolff-[2+2]
Me O
Me H
O
C
+
h
Me
Me
Me
(74%)
J. Org. Chem. 1980, 45, 2708.
O
Me
Rearrangement
Carbenes: Reaction with Heteroatoms
Ylide Formation by the Interaction of Carbeneoids
with Carbonyl Lone Pairs
R
O
••
R
R
R
R
O
R
R
R
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.
Dipolar Cycloaddition
R
O
R
R
R
X
Y
R
O
R
R
R
X
Y
Ylide
Dipolar Cycloadditions
Carbonyl Ylids: Dipolar Cycloaddition
Tandem Intramolecular Cyclization–Intermolecular Cycloaddition
R
R
Rh2(OAc)4
O
R
O
N C CO2Et
O
CHN2
CO2Et
O
O
O
O
NPh
CO2CH3
RCHO
O
R
H
R
O
CO2CH3
O
R
NPh
O
O
N
H
CO2CH3
O
O
CO2CH3
O
O
R
O
H
Ylide Dipolar Cycloadditions
Carbonyl Ylids: Dipolar Cycloaddition
Reactions of Diazoimides: [3+2] addition
H
O
Me
O
N
Rh2(OAc)4
Me
Bn
Me
O
PhCH3, 110 °C
N2
COMe
O
N
Bn
O
74%
–N2
O
Me
COMe
N
Bn
H
CH3
O
N
Me
H
Et3SiH / BF3•Et2O
O
OH
Me
Me
CH2Cl2
O
Bn
O
N
H
O
O
Bn
Maier, M. E.; Evertz, K. Tetrahedron Lett. 1988, 29, 1677-1680.
O
O
O
H
O
N
Rh2(OAc)4
Me
PhH, reflux
N2
88%
Me
O
O
N
H
O
Me
O
H
N
O
O
O
N
O
Me
N
N H
N2
H
"high yield"
Padwa et. al. Tetrahedron Lett. 1992, 33, 4731-4734.
68%
Ylide Dipolar Cycloadditions
Carbonyl Ylids: Dipolar Cycloaddition
The Synthesis of Furans
Intermolecular addition to -unsaturated carbonyls
OMe
OMe
O
Et
O
CuSO4
CHN2
160 °C
O
EtO2C
O
2-methoxymethylenecholestanone-3
EtO2C
O
Spencer Tetrahedron Lett. 1967, 1865-1867.
29%
Can you propose a rational mechanism for this transformation?
O
O
O
O
CH3O
O
O
Cu(acac)2
89%
N2
CO2CH3
O
CH3O
HO CO2CH3
Carbonyl Ylids: Dipolar Cycloaddition
Ylide Dipolar Cycloadditions
The Synthesis of Furans
Intermolecular addition to -unsaturated carbonyls
OMe
OMe
O
Et
O
CuSO4
CHN2
160 °C
O
EtO2C
O
2-methoxymethylenecholestanone-3
EtO2C
O
Spencer Tetrahedron Lett. 1967, 1865-1867.
29%
Can you propose a rational mechanism for this transformation?
O
O
O
CH3O
O
O
O
O
Cu(acac)2
89%
N2
CH3O
CO2CH3
HO CO2CH3
O
O
O
O
O
O
O
CH3O
CH3O
CO2CH3
CO2CH3
Hildebrandt, Tetrahedron Lett. 1988, 29, 2045-2046.
O
Ylide Rearrangement
Stevens Rearrangement ([1,2] alkyl shift)
O
R2
N
R1
N2
O
O
Rh2(OAc)4
West, JACS 1993 1177
N
R1
R2
N
R2
R1
Ring Expansion
Ring expansion reactions
CO2Et
Cu(I)
S
S
CO2Et
N2
TfO
KOt-Bu
S
S
CO2Et
72%
DBU
S
EtO2C
O
OH Methynolide has been synthesized by Vedejs
using this ring-expansion methodology
Me
O
Me
Me
Et
50%
72%
Me
HO
S
CO2Et
O
Vedejs, JACS 1989, 111, 8430