fritsch-buttenberg-wiechell rearrangement
DESCRIPTION
Fritsch-Buttenberg-Wiechell Rearrangement. Vinylcarbenoid. Vinylcarbene. A Mechanistic Odyssey in the Realm of Vinylcarbenes & Vinylcarbenoïds (Journey through the life of reactive intermediates). Leading references Knorr, R, Chem. Rev. 2004 , 104 , 3795-3849 - PowerPoint PPT PresentationTRANSCRIPT
NOH
NOH2
H+ N N
H2O
NOH2H
NOHH
NOHH
NO
- H+
Fritsch-Buttenberg-Wiechell RearrangementFritsch-Buttenberg-Wiechell Rearrangement
Ar
Ar Br
H
Ar
Ar Br
K
KOt-Bu
Ar
Ar
- KBr
Ar Ar
Vinylcarbenoid Vinylcarbene
A Mechanistic Odyssey A Mechanistic Odyssey in the Realm ofin the Realm of
Vinylcarbenes & VinylcarbenoïdsVinylcarbenes & Vinylcarbenoïds
(Journey through the life of reactive intermediates)
Leading referencesKnorr, R, Chem. Rev. 2004, 104, 3795-3849
Braun, M. Angew. Chem. Int. Ed. 1998, 37, 430-451
1) General consideration about FBW rearrangement2) Free vinylcarbene formation
GeneralFrom vinyl triflatesFrom diazoalkenesFrom iodonium ylidesFrom vinyl halides
3) Vinylcarbenoids formationGeneral considerationsStrained cycles
OutlineOutline
FBW : GeneralFBW : General
Discovered in 1894 by Fritsch, Buttenberg and Wiechell
Retro FBWPossible in gaz phase at >650C but generaly very disfavored.
Exeption : very strained alkynes
1.5 kcal/mol
47 kcal/mol
H
H
H
H
R1
R2
SP
SP2
+
-
H
Br
KOt-Bu
Vinylcarbenes (alkylidenecarbene) caracteristicsVinylcarbenes (alkylidenecarbene) caracteristics
Spin multiplicity
Electrophilicity/nucleophilicity
Determined by examination of the [1+2] reaction of vinylcarbene with a serie of substituted styrenes.
S0 S1 T1
S0 state confirmed by stereochemistry of addition to double bond and theorical calculations
= -0.75
Vinylcarbene are mildly electrophilic species
Stang, P. Chem. Rev. 1978, 78, 383
Association with Metals
Do not seem to have much influence.
Steric effects
The [1+2] addition of vinylcarbenes is sensible to hinderance on the double bond (tetrasubstitued alkenes reacts slowly)
Vinylcarbenes (alkylidenecarbene) caracteristicsVinylcarbenes (alkylidenecarbene) caracteristics
R R
R R
R
RR R
R R
R
R
ON
O
NO
R2R1
NN
Ph
R1
O
R2
OTf
R
R
H
N2
R
R
H
I
R
R
H
Ph
BF4
X
R
R
H
Generation of vinylcarbenesGeneration of vinylcarbenes
OTf
R
R
H
Base
( elimination) R
R
NitrosocarbonamidesN-(aziridyl)aldimines
Vinyl triflates
Diazoalkenes
Iodonium Ylides1-Halogenoalkenes
Synthesis of vinyl triflatesSynthesis of vinyl triflates
Ar
Ar Ar
N NNAc
Ar
Ar
Ar Ar
OTfTfOH
R
R TfOH H
Ar Ar
OTf
O
RH
Tf2O R
R R
OTf
R R
O
RH
R
R R
OTMS
R R
TMSCl
Et3N
1) MeLi
2) Tf2O
R
R R
OTf
1
2
3
4
Stang, P. J. Acc. Chem. Res. 1978, 11, 108
Deprotonation is effected in polar solvent at or below 0CMost used base : KOt-Bu
R
R H
OTf R
R D
OTf
KOt-Bu
t-BuOD/pentaneX
R
R H
OTf R
R K
OTf
KOt-Bu
X
To know if a deprotonation is at equlibrum, perform the reaction in adequate deuterated solvent and perform NMR of residual starting material
Driving force to high energy carbene is probably the large pKa difference between KOt-Bu and KOTf
pKa (DMSO)
t-BuOH 29.4
TfOH -13
R
R H
OTf+ KOt-Bu
R
R+ KOTf + t-BuOH
Deprotonation of vinyl triflatesDeprotonation of vinyl triflates
Carbenes from vinyl triflates : Common side-productsCarbenes from vinyl triflates : Common side-products
R
R K
OTf
Ot-Bu
R
RK
OTf
Ot-Bu
negative charge to LG!
R
R Ot-Bu
K
inversion
R
R
R
R
H
Ot-But-BuOH
"OH insertion"
Addition of nucleophilic solvents
THF can act as Lewis base and add on the carbene to gives an oxonium ion that can be opened by alcohols
Me
Me OTf
H KOt-Bu
THF
Me
Me
O
Me
Me O
ROH Me
Me OOR
H
1R
R Ot-Bu
H
via
2
Carbenes from vinyl triflates : Comparative studiesCarbenes from vinyl triflates : Comparative studies
Me
Me Me
Me
[ 1+2] Me
Me MeMe
Me
Me Ot-Bu
H
t-BuOH
OH insertion
85
:
15
Me
Me
[ 1+2] Me
Me MeMe
Me
Me SiMePhNap
H
HSiMePhNap
SiH insertion
85
:
15
Me
Me
Comparaison between [1+2] and insertion
Carbenes from vinyl triflates : Comparative studiesCarbenes from vinyl triflates : Comparative studies
General reactivity order:
H & Ph migration > [1+2] > OHinsert = SiHinsert > 1,5-CHinsert
(H)Ph
Me presence oft-BuOH or R3SiH
Me
Me
Me Ph(H)
only product
H
MeH
HHBu H
Me
H
100 : 0
How to prove the intermediacy of carbeneHow to prove the intermediacy of carbene
Like carbenes, carbenoïds can perform OH insertion and [1+2]. Witch one is the reactive species?
Et
Me OTf
H
Et
Me H
OTf
KOt-Bu
KOt-Bu
Et
Me OTf
K
Et
Me K
OTf
Et
Me
E
Z
Products
Product
From E 18.8% 7.3% 31.8% 42.1%
From Z 18.8% 7.7% 32.0% 41.6%
Et
Me
H
Ot-Bu
Et
Me
Ot-Bu
H
Et
Me
Et
Me
If two precursor can lead to product directly or via a common intermediate, an identical products distribution for each is a necessary albeit not sufficient condition for the existence of the common intermediate
Stang, P.J.; Mangum, D.P.F.; Haak, P. J. Am. Chem. Soc. 1974, 96, 4562
Conclusion: Vinyl triflates probably generates free carbenes
How to prove the intermediacy of carbene, part 2!How to prove the intermediacy of carbene, part 2!
Me
Me OTf
H
Me
Me N
H
NTs
KOt-Bu
Me
Me OTf
K
Me
Me
Me
Me
Ratio A
Ratio A
Ratio B
Ph
Ph
Ph
Starting Material
1 1.52
1 1.52
Me
Me N
H
NTs
Me
Me OTf
H
Ph
MeMe
MeMe
Conclusion
Vinyl triflates generates free carbenes
A way to prove a reaction intermediate is to generate it from at least 2 independent sources. If the reactivity of that intermediate remain the same, it is probably real.
Carbenes from diazoalkenesCarbenes from diazoalkenes
R
R N
H
NX
R
R N2
R
RR
RN2
base
Deprotonated diazoalkenes can be considered as nitrogen complex of carbenes
Synthesis
R1 R2
O
N2
P(OMe)2
O
H+O P(O)(OR)2
R2
R1
N2
N2R2
R1
R1 R2
O
N2
SiMe3H+O SiMe3
R2
R1
N2
N2
R2
R1
Seyfert-Gilbert reagent (DAMP)
Peterson olefination
1
2
Carbenes from diazoalkenesCarbenes from diazoalkenes
• Similar to carbenes from vinyl trilfates
• H and Ar migrate easily and the alkyne is obtained in good yield. (40 – 90%) Exception:
O2N
(destabilize + charge in the transition state)Side-reactions have enough time to occur.
Me
MeSince alkyl groups do not migrate well, OH & NH insertion reaction can occur in good yield.
R1
R2
OR1
R2
NR2 R1
R2
Owork-up
FBW
Insertion
1,5-CH insertion of vinylcarbenes1,5-CH insertion of vinylcarbenes
Intramolecular 1,5-CH insertion are possible with vinylcarbenes with an appropriate chain.Competition experiments gave the following (not surprising) selectivity:
Primary1
Secondary30
Benzylic76
Tertiary240
fastslow
R H
ORROWorks well :o)
The strange case of amides migration and CH insertionThe strange case of amides migration and CH insertion
The problem: Like H and Ar, amides migrate very well. However, carbenes with tertiary amide do prefer 1,5-CH insertion of primary H
MeN
O
Me
PhN2
N
O
Me
Ph
N
O
Ph
Me
O
N
Me
Ph
35%48%12%
Insertion into chiral CH occur with >99% retention
R
H
RR
The strange case of amides migration & CH insertionThe strange case of amides migration & CH insertion
N
O
Me
HH
H N
O
Me
H
H
H
E
CH3
NH2
O
MeN
Me
Me
MeN
Me
PhMeOCH insertion : 0%Migration : N/A
MeOHAmide group is essential!
Answer comes from conformational analysis
MeN
O
Me
PhN2
1. Dipole minimization
MeN
O
Me
PhN2
MeN
O
Me
N2
Ph
2. Amide conformation
3. Rate of amide rotation is not competitive with the rate of decomposition and CH insertion
Stabilisation of radical transition state
Other sources of diazoalkenes & vinylcarbenesOther sources of diazoalkenes & vinylcarbenes
Nitrosocarbonamides
N-(aziridyl)aldimines
• Carbene are produced in medium yield• SM is difficult to prepare
ON
RR
O
NO Base or
- CO2
- OH- R
R H
N2+
- H+
R
R
N2+ R
R
H
B
NR
R
NO
NR
R
NOH
BH
Not very appealing…
NN
Ph
O
H
R H
N2O
H
R H
toluene, reflux
- styrene
H
N2
O
H
R
H
N2
HO
H
R
- N2
HO
H
R
H
R
OH
>90%
Kim, S.; Cho., C. M. Tetrahedron Lett. 1994, 35, 8405
Carbenes from iodonium ylidesCarbenes from iodonium ylides
R I
R
R
94º94º"T" Shaped
R
I
Cl
Cl Ph Square Planar
R
R
I
Ph
IR
R
Ph R
R- IPh
Structure Stability
Relatively stable if R = EWGC-I do not have a double bond character
If R is not EWG, compound isn't isolable but can be generated in situ
Iodonium ylides synthesisIodonium ylides synthesis
R
SnBu3 PhIO(CN)OTf
R
IPh
R = CN, Cl, ArSO2, C(O)R, R2NC(O), etc...
The less nucleophilic is the counter ion, the more stable is the alkynyl iodonium species
nucleophile
I Ph
Nu
R
From stannylacetylenes:
R
IPh
Soft site
Hard site
Good nucleophiles: Activated carbonyl, NR2, N3, PPh3, Phenoxydes, sulfonates, phosphonates, carboxylates
Bad nucleophiles: Enolates, alkoxydes, RLi
Iodonium ylides conformational stabilityIodonium ylides conformational stability
Me
Ph
I Ph Me
Ph I Ph?
Me
Ph
I Ph Me
Ph I PhH
H
NaOAcNaOAc
Me Ph
Result: Z ylide form the alkyne 3.7 times faster than E ylideConclusion: No fast equilibrium of ylides
Me
Bn H
IPh
Me
Bn
H
IPh
Me
Bn
Bn
Me
H
SPh
Ph
Bn
Me
H
S
E:Z = 31:69 from A29:71 from B
E:Z = 38:62 from A36:64 from B
SPh2 THT
A B
Carbene formation?Carbene formation?
Vinylic carbocation formation?Vinylic carbocation formation?
R
R
I Ph
H
R
R HI Ph+
?H2O, MeOH
I
H
Ph
H2O, MeOH
H
OH
O
H2O
I
H
Ph
H
achiral
H
H2O
O
Result: Complete retention of configurationConclusion: No vinylic carbocation
One way to choose between two mechanism is to perform a reaction on a chiral substrate that form an achiral intermediate according to one mechanism and not according to the other.
Chiral product = No achiral intermediateRacemic product = Achiral intermediate
IPh is one of the best known leaving group.
• 106 times better than Triflate• 1012 times better than Tosylate
R
H I
H
Ph
Me4NCl
MeCN
R
H H
Cl
+R
H
SNV E2syn
A B
R
H I
H
Ph
R
H I
H
Ph
R
H I
H
Ph
R
H I
H
Ph
ClCl ClCl
Cl- Cl-
R
H H
Cl
R
H
KA[Cl-] KB[Cl-] KC KD
fast
Iodonium ylides in nucleophilic mediumIodonium ylides in nucleophilic medium
Low [Cl-] = B is favored
Medium [Cl-] = A is favored
High [Cl-] = B is favored
Note: For large R, ligand coupling mechanism leads to Cl insertion with retention
Carbenes from 1-HalogenoalkenesCarbenes from 1-Halogenoalkenes
R2
R1
R2
R1 H
Br
Base
pKa > 30
The Base :
Base cannot be BuLi because Br-Li exchange is faster than deprotonation
Bad bases = NaH, i-Pr2NEtGood bases = NaHMDS, KHMDS, KOt-Bu
Deprotonation :
R
R H
Br R
R M
Br
base
R
R M
Br
R
R
Bu
Bu
I Ph
HKOt-Bu
KOt-Bu
Bu
Bu
Br
H
Bu
Bu
Bu
2
1Something must accelerate the FBW migration.
: 41
: 1
Competion between Carbene & CarbenoidCompetion between Carbene & Carbenoid
primary CHsecondary CHtertiary CH
154240
130240
Br IPh
Similar ratio show that CH insertion is only performed by the carbene
FBW vs 1,5-CH insertion
1,5-CH insertion : primary vs secondary vs tertiary
X
HH
RR
H3C Pr
RR
CHR2
+base
Me
R2
R1
Br
HHKOt-Bu
FBW + 1,5-CH insertion + OH insertion
Me
R2
R1
Br
HHKOt-Bu
Me
R2
R1
Br
H
Me
R2
R1
H
MeR1R2
FBW
t-BuOH
Me
R2
R1
H
OtBu
H1,5-CH
insertion H
R1R2
Me
Summary of reactivitySummary of reactivity
Half-Meeting traditional question(+ beer time)
Propose a mechanism for the following transformation
700 C
Half-Meeting traditional question answer(beer time is over…)
H
H
H
intramolecular
1,5-CH insertion
Me
H
4electrons
electrocyclicreaction
1,5-H migration
Roger Brownequilibrium
Brown, R. F. C. et al. Aust. J. Chem. 1974, 27, 2373
Ar
Ar Cl
Li
108.7º
137.1º
112.6º
Vinylcarbenoids: GeneralVinylcarbenoids: General
Structure
R
R R
R
R1
R2R
R Cl
Li Li-13C coupling constant show that Li,Br carbenoïds are monomers in THF
RS
RL K
Br RS
RL Br
KX
E Z
RS
RL Cl
Br RS
RL Cl
Li
MeLi
RS
RL Br
Cl RS
RL Li
Cl
MeLi
XResidual SM can catalyse the
isomerisation via fast M-Br exchange.
Stability
Boche, G.; Marsch, M.; Muller, A.; Harms, K. Angew. Chem. Int. Ed. Engl. 1993, 32, 1032Hafner, K. Pure Appl. Chem, 1990, 62, 531
Me
Me Br
Br
MeLi
- MeBrMe Me
Me
Me Me
Br Me
Me Me
H
Me
Me
Me
Me+ + +
Vinylcarbenoids: Common side-productsVinylcarbenoids: Common side-products
Me
Me Br
Br
MeLi
f ast Me
Me Li
Br
MeBr
SN2
slow Me
Me Me
Br
Me
Me Li
Br50% of the reaction+ Me
Li
Me
Me Me
Li Me
Me Me
H
Work-UpMeLi
Me
Me Li
Br Me
Me Li
BrLi
BrMe
MeMe
Me
Me
Me
Me
Me
MeLi
K
BrPartial heterolysis of anti-Br creates "empty" orbital
Product
H
Br
*Br
H
*Br
H*
2.6 : 1
+
How to explain this?
Mechanistic black holeMechanistic black hole
H
Br
KOt-BuBr
H
Br
H1
153
Migration of CMe2 (anti)
Migration of CH2 (syn)
+
trace
D
Br
KOt-Bu
DOt-Bu
Should come from the migration of CH2 without net breaking the C-Br bound.
“Thus, the detailled mechanisms of both syn and anti migrations are open problems.”- R. Knorr -
Erikson, K. L. J. Org. Chem. 1971, 36, 1031Samuel, S. P.; Niu, T.; Erikson, K. L. J. Am. Chem. Soc. 1989, 111, 1429
Strained cycle formationStrained cycle formation
H2C
Expansion from 7 to 8 membered ringExpansion from 7 to 8 membered ring
Usually do not occur. (Remember: alkyl groups do not migrate well…)
Br
H
KOt-Bu Ot-Bu
H
Cl
H
PhLi PhLi Li
Ph
23%
Expansion from 6 to 7 membered ringExpansion from 6 to 7 membered ring
Cyclobutyne is the smallest stable cyclic alkyne
Do not occur.
Pr
Pr
Cl
H
1) PhLi
2) CO2
Pr
Pr
Ph
H
+
15% 19%
Curtin, D. Y.; Richardson, W. H. J. Am. Chem. Soc. 1959, 81, 4719
Curtin, D. Y.; Richardson, W. H. J. Am. Chem. Soc. 1959, 81, 4719
Expansion from 5 to 6 membered ringExpansion from 5 to 6 membered ring
norborynebenzyne
Seem to occur, the cycloalkyne can be trapped with various agentsStrange behavior due to high ring strain
cyclohexyne
t-Bu
t-Bu
H
OTf
t-Bu
t-Bu
t-Bu
t-Bu
* *
*
t-Bu
t-Bu
H
Cl
maybe via Z isomer
Benzyne1
2 Norboryne
Cl
H
Cl
H
t-BuLi
Li
Cl
O
O
Ph
Li
PhLi
PhLi
Cl
H
Li
R
RLi
- LiCl
HR
HR
Expansion from 5 to 6 membered ringExpansion from 5 to 6 membered ring
Expansion from 5 to 6 membered ringExpansion from 5 to 6 membered ring
2 Cyclohexyne
H
Br
KOt-Bu K
Br
K
Br
O
O
Gilbert, J. C.; Baze, M. E. J. Am. Chem. Soc. 1983, 105, 664 Bachrach, S. M.; Gilbert, J. C.; Laird, D. W. J. Am. Chem. Soc. 2001, 123, 6706
Expansion from 4 to 5 membered ringExpansion from 4 to 5 membered ring
Cyclopropyne is so strained that it can be considered as a 1,2-dicarbene(and react like so)
Seem to occur, the cycloalkyne can be trapped with various agentsStill more strange behavior due to high ring strain
N2
- N2
n-BuOH
O
O
O
Ot-Bu
H
Ot-Bu
H
1 : 1
1 : 1
**
Expansion from 4 to 5 membered ring, part 2Expansion from 4 to 5 membered ring, part 2
Br
Br
Br
Br
BuLi
BuLi
TfO
Me3Si
BuLi
TBAF
N2
[2+2] [4+2]
+
Cyclopentyne reactivity depend of the way it is generated
Source [2+2] [4+2]
Organometalic precursor
12 - 54 1
Standard precursor
1 1.5
Explanation: There must be an other intermediate.
Variation of M and X on the organometallic precursor should be done as well as 13C labeling.
. LiBr
Gilbert, J. C.; McKinley, E. G.; Hou, D-R. Tetrahedron 1997, 53, 9891
Expansion from 3 to 4 membered ringExpansion from 3 to 4 membered ring
Expansion from 2 to 3 membered ringExpansion from 2 to 3 membered ring
Do not occur.
“Cyclopropyne ring was calculated not to be a local minimum”–Rudolf Knorr
Do not occur.
Theorical existence of cyclobutyne is controversial
Johnson, R. P.; Daoust, K. J. J. Am. Chem. Soc. 1995, 117, 362
Jonas, V.; Böhme, M.; Frenking, G. J. Phys. Chem. 1992, 96, 1640
H2C X
X
CH insertion of carbenoïdsCH insertion of carbenoïds
1,5-CH insertion are rare for vinylcarbenoïds.The corresponding carbene can never be excluded
Me
Cl
H
H
H n-BuLi
Me
Me
Bu
H
H
H
62% 13%
Me
Cl
H
Me
Me n-BuLi
Me
MeMe
1,4-CH insertion0%
MeMe
1,6-CH insertion0%
Me
[1+2]intramolecular
25%
Fisher, R. H.; Baumann, M., Köbrich, G Tetrahedron Lett. 1974, 1207
Migration of unsaturated substituentsMigration of unsaturated substituents
MePh
Cl
H(Z)
BuLi
Me
Ph
(Z) Me+
1,6-CH insertion
Me Li
HH
Ph
Without going throught:
Ph
M
Cl
R
Donor substituants accelerates reaction
Ph M
R
Ph R
Fienemann, H.; Köbrich, G Chem. Ber. 1974, 107, 2797
Carbenes vs. Carbenoids : kineticCarbenes vs. Carbenoids : kinetic
R1
R2 M
X
products
R1
R2+ M+X-
kel
k-el
kcc
- MXkccmx
2 cases:
At low temperature, carbenoïds are kinetically stable and can react in a plain bimolecular reaction.
The carbene reacts much more faster than the carbenoid
1
2
Case 1: Stable carbenoid react in a bimolecular reaction without rate-controlling intermediate
Case 2: Carbenoid is in fast equilibrium with the carbene and only the carbene react in a bimolecular reaction
ccmxrate k carbenoid reagent
0ccmxk
ccrate k carbene reagent
...
el
el
el
el
carbene MXk
k carbenoid
k carbenoidso carbene
k MX
Decreased rate for increased MX concentration
cc el
el
carbenoid reagentk krate
k MX
Independence of the rate and MX concentration
Carbenes vs. Carbenoïds : kineticCarbenes vs. Carbenoïds : kinetic
R1
R2 M
X
products
R1
R2+ M+X-
kel
k-el
kcc
- MXkccmx
Summary of migration capability of vinylcarbenoidsSummary of migration capability of vinylcarbenoids
H
Cl
BuLi
-90 to -60> -60 : Side products formation starts to compete
Bu
HFrom SNV or Add/Ell
R2N
R2N Cl
LiR2N NR2
via "onium" intermediate
R
PhS Cl
LiR SPh
via "onium" intermediate
Heteroatom migration
R
Et3SiO Cl
LiR OSiEt3X
O Si
RH
Me
Et Et
Small ring migration
Newman, M. S.; Gromelski, S. J. J. Am. Chem. Soc. 1972, 37, 3220
i-PrO
Ph Li
I
1) sec-BuLi (excess) (-20 to RT)
2) MeI i-PrO
Ph Me
Mei-PrO Ph
8%34%
+
Summary of migration capability of vinylcarbenoidsSummary of migration capability of vinylcarbenoids
t-Bu
LiO Br
Br t-BuLi t-Bu
LiO Br
LiLiO t-Bu
ROH
RO
O
t-Bu
Alkoxyde do not migrates, but helps the migration of other groups
Alkoxyde migration
Enol ether migration
Kowalski, C. J.; Reddy, R. E. J. Org. Chem. 1992, 57, 7194
Note
Usualy, heavier halogen = lower decomposition tempex.:
R
F X
Li
X = F : -5CX = Cl : -50C
Explanation
OiPr destabilize the SP center in the transition state via its inductive effect (s = -0.12) even if it is a strong p-donor. Calculations show then O-iPr do not solvate the Li atom
SummarySummary
Good migrating groups in the FBW rearrangement are H and Ar
1,5-CH insertion of vinylcarbenes & vinylcarbenoids can be a clean reaction
Vinyl triflates, vinyl diazonium salts and vinyl iodonium ylides produce free vinylcarbenes
1,1-bromolithioolefins produce a mix of free carbenes and carbenoids
Vinylcarbenoids are stable at low temperature
Cycloalkynes can be produced in situ from vinylcarbenes & vinylcarbenoids
Vinylcarbenoids behavior is mechanistically underdeveloped
The End