the claisen rearrangement
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The Claisen RearrangementLecture Notes
O O O
Key Reviews:
F. E. Zeigler, Chem. Rev. 1988, 88, 1423.
P. Wipf in Comprehensive Organic Synthesis, 1991, vol. 5, p. 827.
A. M. Castro, Chem. Rev. 2004, 104, 2939.
[3,3]
[3,3]-Rearrangements: The Claisen and Cope Reactions/Rearrangements
J. Org. Chem. 1976, 41, 3497; J. Org. Chem. 1976, 41, 3512; J. Org. Chem. 1978, 43, 3435.
O O
OO[Cope
rearrangement]
[Claisenrearrangement]
Δ
O O
The Claisen Reaction: Initial Discovery
CO2Me distillationNH4Cl
CO2Me
L. Claisen, Chem. Ber. 1912, 45, 3157.
R1 R2
OH
R1 R2
O R3X
R1 R2
O R3X
R1
O
X
R2
R3
Reaction can be regarded as the sigmatropic homologation of an allylic alcohol,meaning the migration of a sigma bond across a conjugated pi system to a new position.
Bonds Broken2 C C1 C O
Bonds FormedC CC OC C
111
[3,3]
O O
The Claisen Reaction: Initial Discovery
CO2Me distillationNH4Cl
CO2Me
L. Claisen, Chem. Ber. 1912, 45, 3157.
R1 R2
OH
R1 R2
O R3X
R1 R2
O R3X
R1
O
X
R2
R3
Reaction can be regarded as the sigmatropic homologation of an allylic alcohol,meaning the migration of a sigma bond across a conjugated pi system to a new position.
Bonds Broken2 C C1 C O
Bonds FormedC CC OC C
111
[3,3]
The Claisen Reaction: Why is it So Useful?
L. Claisen, Chem. Ber. 1912, 45, 3157.
R1 R2
OH
R1 R2
O R3X
R1 R2
O R3X
R1
O
X
R2
R3[3,3]
1. Experimental procedures are very reliable
2. Compatible with a wide range of functional groups
3. Substrates are readily made, and the δ,γ-unsaturated product can be chemoselectively adjusted at either end (alkene or carbonyl) to give further materials
4. High stereoselectivity in formation of double bonds and chiral centers.
OO O O
Key points:
The Claisen Reaction: Why is it So Useful?
L. Claisen, Chem. Ber. 1912, 45, 3157.
R1 R2
OH
R1 R2
O R3X
R1 R2
O R3X
R1
O
X
R2
R3[3,3]
1. Experimental procedures are very reliable
2. Compatible with a wide range of functional groups
3. Substrates are readily made, and the δ,γ-unsaturated product can be chemoselectively adjusted at either end (alkene or carbonyl) to give further materials
4. High stereoselectivity in formation of double bonds and chiral centers.
OO O O
Key points:
The Claisen Reaction: Why is it So Useful?
L. Claisen, Chem. Ber. 1912, 45, 3157.
R1 R2
OH
R1 R2
O R3X
R1 R2
O R3X
R1
O
X
R2
R3[3,3]
1. Experimental procedures are very reliable
2. Compatible with a wide range of functional groups
3. Substrates are readily made, and the δ,γ-unsaturated product can be chemoselectively adjusted at either end (alkene or carbonyl) to give further materials
4. High stereoselectivity in formation of double bonds and chiral centers.
OO O O
Key points:
The Claisen Reaction: Substrate Preparation
J. Org. Chem. 1976, 41, 3497; J. Org. Chem. 1976, 41, 3512; J. Org. Chem. 1978, 43, 3435.
OH R
MeO OMe
R = H, Me, alkyl
p-TsOH,xylene, Δ
O
R OMe
O
R
O
R
Potential drawbacks
Competing acid-catalyzed reactions with resident functional groups
If R is an alkyl group other than methyl, regiochemicalproblems in vinyl ether synthesis can occur
[3,3]
The Claisen Reaction: Substrate Preparation
S. D. Burke and co-workers, Strategies and Tactics in Organic Synthesis 1987, 2, 57.
OH
Hg(OAc)2O
OEtHgOAcOEt
-[EtOHgOAc]
O O[3,3]
A much milder procedure for cases where substrates cannot tolerate acid and heat;in the case below it succeeded where others failed.
HH
OH
OO
Hg(OAc)2,
OEt
o-xylene,240 oC,
sealed tube
HH
OO
O
Δ
The Claisen Reaction: Substrate Preparation
S. D. Burke and co-workers, Strategies and Tactics in Organic Synthesis 1987, 2, 57.
OH
Hg(OAc)2O
OEtHgOAcOEt
-[EtOHgOAc]
O O[3,3]
A much milder procedure for cases where substrates cannot tolerate acid and heat;in the case below it succeeded where others failed.
HH
OH
OO
Hg(OAc)2,
OEt
o-xylene,240 oC,
sealed tube
HH
OO
O
Δ
The Claisen Reaction: Substrate Preparation
P. T. Lansbury, N. Y. Wang, J. E. Rhodes, Tetrahedron Lett. 1971,12, 1829 and 1833F. Johnson, K. G. Paul, D. Favaro, R. Ciabatti, U. Guzzi, J. Am. Chem. Soc. 1982, 104, 2198.
OMeO2C
H
H
ClOH
MeO OMe
p-TsOH, Δ
In both cases the Claisen reaction occurs on the more accessible, convex face of the molecule
OMeO2C
H
H
Cl
OMeO2C
H
H
Cl
CN
O
KH,Br
CN
OΔ
O
NC
O
Li, NH3;MeI
[3,3]
[3,3]
The Claisen Reaction: Substrate Preparation
P. T. Lansbury, N. Y. Wang, J. E. Rhodes, Tetrahedron Lett. 1971,12, 1829 and 1833F. Johnson, K. G. Paul, D. Favaro, R. Ciabatti, U. Guzzi, J. Am. Chem. Soc. 1982, 104, 2198.
OMeO2C
H
H
ClOH
MeO OMe
p-TsOH, Δ
In both cases the Claisen reaction occurs on the more accessible, convex face of the molecule
OMeO2C
H
H
Cl
OMeO2C
H
H
Cl
CN
O
KH,Br
CN
OΔ
O
NC
O
Li, NH3;MeI
[3,3]
[3,3]
The Claisen Reaction: Substrate Preparation
XXX, Tetrahedron Lett. 1971, 1829 and 1833XXX, J. Am. Chem. Soc. 1982, 104, 2198.
HO O HOO
OH OH O
Aromaticity can be broken through the Claisen rearrangement
Brbase,
[3,3] [Keto-enol
tauto-merization]
The Claisen Reaction: Substrate Preparation
XXX, Tetrahedron Lett. 1971, 1829 and 1833XXX, J. Am. Chem. Soc. 1982, 104, 2198.
HO O HOO
OH OH O
Aromaticity can be broken through the Claisen rearrangement
Brbase,
[3,3] [Keto-enol
tauto-merization]
The Claisen Reaction: Stereochemical Considerations
P. A. Bartlett, Tetrahedron 1980, 36, 2.
O O
O
OO O O
O O
OO O
Reactions proceed through chair-like transition states
[3,3]
[3,3]
[3,3]
The Claisen Reaction: Stereochemical Considerations
P. A. Bartlett, Tetrahedron 1980, 36, 2.
O O
O
OO O O
O O
OO O
Reactions proceed through chair-like transition states
[3,3]
[3,3]
[3,3]
The Claisen Reaction: Stereochemical Considerations
P. A. Bartlett, Tetrahedron 1980, 36, 2.
O O
O
OO O O
O O
OO O
Reactions proceed through chair-like transition states
[3,3]
[3,3]
[3,3]
The Claisen Reaction: Stereochemical Considerations
L. Claisen, Chem. Ber. 1912, 45, 3157.
O
Me
OMeOMe
O Me
Pre-existing chirality determines the stereoselectivity of the rearrangement
MeH Me
H
MeH Me
OMe
HMe O
Me
Me
HMe OMe
As a general rule, unless there are strange geometrical constraints(i.e. the reaction proceeds in a chair, not a boat, transition state),
E-olefins result from the Claisen rearrangement
[3,3]
[3,3]
The Claisen Reaction: Stereochemical Considerations
L. Claisen, Chem. Ber. 1912, 45, 3157.
O
Me
OMeOMe
O Me
Pre-existing chirality determines the stereoselectivity of the rearrangement
MeH Me
H
MeH Me
OMe
HMe O
Me
Me
HMe OMe
typicallynot observed
As a general rule, unless there are strange geometrical constraints(i.e. the reaction proceeds in a chair, not a boat, transition state),
E-olefins result from the Claisen rearrangement
majorproduct
[3,3]
[3,3]
XX
The Claisen Reaction: Stereochemical Considerations
C. L. Perrin, D. J. Faulkner, Tetrahedron Lett. 1969, 2783.
O
Me
OMeOMe
O Me
Pre-existing chirality determines the stereoselectivity of the rearrangement
MeH Me
H
MeH Me
OMe
HMe O
Me
Me
HMe OMe
X
X
X = H, E/Z = ~9:1X = OEt or NMe2, E/Z = >99:1
X
X
X
Preference for equatorial position of substituents correlates with A-values
[3,3]
[3,3]
XX
The Claisen Reaction: Stereochemical Considerations
C. L. Perrin, D. J. Faulkner, Tetrahedron Lett. 1969, 2783.
O
Me
OMeOMe
O Me
Pre-existing chirality determines the stereoselectivity of the rearrangement
MeH Me
H
MeH Me
OMe
HMe O
Me
Me
HMe OMe
typicallynot observed
majorproduct
X
X
X = H, E/Z = ~9:1X = OEt or NMe2, E/Z = >99:1
X
X
X
Preference for equatorial position of substituents correlates with A-values
[3,3]
[3,3]
The Claisen Reaction: Stereochemical Considerations
A. S. Franklin, L. E. Overman, Chem. Rev. 1996, 96, 505
Pre-existing chirality determines the stereoselectivity of the rearrangement,even if multiple substituents are present
MeOBn
MeO
OMe
LDA, HMPA;TBSCl
MeOBn
MeO
OTBSMe
OMe
Me
TBSO
MeOBn
OMe
Me
TBSO
MeOBn
Me
MeMe
O
TBSOOBn
MeOH,HCl
(90%overall)(7:1 d.r.)
Me
MeMe
O
MeOOBn
-78 oCto 23 oC
[3,3]
The Claisen Reaction: Stereochemical Considerations
A. S. Franklin, L. E. Overman, Chem. Rev. 1996, 96, 505
Many different ways to access chiral allylic alcohols:
R1 R2
OH
R1 R2
O R3X
R1 R2
O R3X
[3,3]
* *
Chiral pool building block
Resolution of achiral starting material
Asymmetric reduction of α,β-unsaturated system
The Claisen Reaction: Stereochemical Considerations
A. S. Franklin, L. E. Overman, Chem. Rev. 1996, 96, 505
Many different ways to access chiral allylic alcohols:
R1 R2
OH
R1 R2
O R3X
R1 R2
O R3X
[3,3]
* *
Chiral pool building block
Resolution of achiral starting material
Asymmetric reduction of α,β-unsaturated system
The Roche Synthesis of α-Tocopherol
J. Org. Chem. 1976, 41, 3497; J. Org. Chem. 1976, 41, 3512; J. Org. Chem. 1978, 43, 3435.
OH
OH
OH
Na, NH3
Lindlarreduction
OH
OH
[resolution]
X
The Roche Synthesis of α-Tocopherol
J. Org. Chem. 1976, 41, 3497; J. Org. Chem. 1976, 41, 3512; J. Org. Chem. 1978, 43, 3435.
OH
OH
O
O
X
X
X = OMe, OTBS, or NMe2O
X
O
O
X
Δ
Δ
97-99% e.e.
[3,3]
[3,3]
The Roche Synthesis of α-Tocopherol
J. Org. Chem. 1976, 41, 3497; J. Org. Chem. 1976, 41, 3512; J. Org. Chem. 1978, 43, 3435.
O
X97-99% e.e.
OH
[Repeat of process]
O
X94-99% e.e.
O
OH
α-tocopherol
The Johnson Orthoester Claisen Rearrangement: A Useful Variant of the Claisen Reaction
W.S. Johnson, L. Werthemann, W.R. Bartless, T.J. Brocksom, T.-T. Li, D. J. Faulkner, M.R. Petersen,J. Am. Chem. Soc. 1970, 92, 741.
OEt
EtO OEt
OEt
EtO OEt
OEt
OEtacid
acid, ΔR
OH
R
O OEtOEt
R
O OEt
R
O OEt
R
O
OEt
R
O
OEt
[3,3]
The Johnson Orthoester Claisen Rearrangement: Key Stereochemical Difference from Eschenmoser Variant
XXX, Chem. Ber. 1971, 104, 3679.
OEt
EtO OEt
Δ
EtOEtO
O
R
ORO
RO
RH
~50%
OEt
X
OH
RO
R
OEt
O
R
OEt
or
EtOEtO
O
R
ORO
RO
RH
~50%
OEt
X
H
H
Stereocontrol can become a concern with non-methyl alkyl chains
The Johnson Orthoester Claisen Rearrangement: Key Stereochemical Difference from Eschenmoser Variant
XXX, Chem. Ber. 1971, 104, 3679.
OEt
EtO OEt
Δ
EtOEtO
O
R
ORO
RO
RH
OEt
X
OH
RO
R
OEt
O
R
OEt
or
EtOEtO
O
R
ORO
RO
RH
OEt
X
H
H
Stereocontrol can become a concern with non-methyl alkyl chains
The Johnson Orthoester Claisen Rearrangement: Key Stereochemical Difference from Eschenmoser Variant
XXX, Chem. Ber. 1971, 104, 3679.
OEt
EtO OEt
Δ
EtOEtO
O
R
ORO
RO
RH
~50%
OEt
X
OH
RO
R
OEt
O
R
OEt
or
EtOEtO
O
R
ORO
RO
RH
~50%
OEt
X
H
H
Stereocontrol can become a concern with non-methyl alkyl chains
Johnson Orthoester Claisen Rearrangements in Synthesis
B. Lythgoe, D. A. Roberts, I. Waterhouse, J. Chem. Soc., Perkin Trans. 1 1977, 2608.
HO
OHOMe
HA,xylene, Δ O
O O
O
O
O
OEt
EtO
CO2EtEtO2C
[3,3]
xylene, Δ[3,3]
squalene
Johnson Orthoester Claisen Rearrangements in Synthesis
B. Lythgoe, D. A. Roberts, I. Waterhouse, J. Chem. Soc., Perkin Trans. 1 1977, 2608.
HO
OHOMe
HA,xylene, Δ O
O O
O
O
O
OEt
EtO
CO2EtEtO2C
[3,3]
xylene, Δ[3,3]
squalene
Johnson Orthoester Claisen Rearrangements in Synthesis
B. Lythgoe, D. A. Roberts, I. Waterhouse, J. Chem. Soc., Perkin Trans. 1 1977, 2608.
O
HBzO
OH
HBzO
OH
HBzO
HBzO
CO2Et
HOWindaus-Grundman ketone
OEt
EtO OEtacid, Δ[3,3]
how? and/or
OMe
Johnson Orthoester Claisen Rearrangements in Synthesis
G. Stork, S. Raucher, J. Am. Chem. Soc. 1975, 98, 1583.
OHO
O O
Me MeO O
Me Me
OOH
O
OMe
O O
Me Me
OO
O
OMe
MeO
OMe
MeO OMe
propanoic acid,140 oC
O
O
O
O
O
OMe
MeMeO O
OO
OMe
MeO2C
Me
OH
OCO2Me
(+)-prostaglandin A2
[3,3]
(86%)
how?
Johnson Orthoester Claisen Rearrangements in Synthesis
C. B. Chapleo, P. Hallett, B. Lythgoe, I. Waterhouse, P. W. Wright, J. Chem. Soc., Perkin Trans. 1 1977, 1211.
O
EtO OEtMe
BzOOH
+
Me
BzOO
O
propanoic acid, xylene, Δ
BzO Me
OO
O
boat t.s. forced byconstraint of rings BzO
O
OHO
=
boat t.s.
S. A. Snyder, Z. Tang, R. Gupta, J. Am. Chem. Soc. 2009, 131, 5744.
HO O
MeO OO
MeMe
ClCl
MeO O
MeO OO
MeMe
OHCl
MeO O
MeO OO
MeMe
OCl
OMe
CH3C(OMe)3, toluene (1:20),propionic acid, 130 °C, 15 h
3. PTSA
1. KOAc, 18-Crown-62. NaH, Me2SO4
(84%overall)
MeO O
MeO OO
MeMe
Cl
CO2Me
[Johnson-Claisenrearrangement]
(72%)
First example of a Claisenrearrangement creating
a quaternary carbon nextto a glycal oxygen
Johnson Orthoester Claisen Rearrangements in Synthesis
The Eschenmosher Amide Acetal Rearrangement: A Useful Variant of the Claisen Reaction
A. Eschenmoser, Helv. Chim. Acta. 1964, 47, 2425.
N
OH
Bz
NMe2
MeO OMe
NMe2
MeO OMe
NMe2
OMeacid
acid, Δ
N
O
Bz
NMe2OMe
N
O
Bz
NMe2
N
O
Bz
NMe2
N
O
Bz
NMe2
NBz
NMe2
O [3,3]
The Eschenmosher Amide Acetal Rearrangement: A Useful Variant of the Claisen Reaction
W. Sucrow, W. Richter, Chem. Ber. 1971, 104, 3679.
NMe2
MeO OMe
Δ
Me2NMe2N
O
R
ORO
RO
RH
NMe2
X
OH
RO
R
NMe2
O
R
NMe2
or
Me2NMe2N
O
R
ORO
RO
RH
NMe2
X
H
H
Stereocontrol can become a concern with non-methyl alkyl chains
The Eschenmosher Amide Acetal Rearrangement: A Useful Variant of the Claisen Reaction
W. Sucrow, W. Richter, Chem. Ber. 1971, 104, 3679.
NMe2
MeO OMe
Δ
Me2NMe2N
O
R
ORO
RO
RH
~95%
NMe2
X
OH
RO
R
NMe2
O
R
NMe2
or
Me2NMe2N
O
R
ORO
RO
RH ~5%
NMe2
X
H
H
Stereocontrol can become a concern with non-methyl alkyl chains
The Eschenmosher Amide Acetal Rearrangement: A Useful Variant of the Claisen Reaction
F. E. Zeigler, J. M. Fang, C. C. Tam, J. Am. Chem. Soc. 1982, 104, 7174.H. F. Strauss, A. Wiechers, Tetrahedron 1978, 34, 127.
HO
OHH
NMe2
MeO OMe
Δ
HO
HO
NMe2
MeO
S
S
HO S
S
NMe2
MeO OMe
Δ
MeO
Me2N O
MeO
Me2N O
O-methyljoubertiamine
(71%)
[3,3]
[3,3]
The Ireland-Claisen Rearrangement: Use of Enolates to Generate Well-Defined Precursors
R. E. Ireland, R. H. Mueller, J. Am. Chem. Soc. 1972, 94, 5897.R. E. Ireland, R. H. Mueller, A. K. Willard, J. Am. Chem. Soc. 1976, 98, 2868.
O
OOHOTMS
O
OTMS
O
Key feature of chemistry is the ability to control enolate
geometry to then controlthe formation of either syn-
or anti- products
OH
O
OH
O
O
OH
O
OH
Z-enolate E-enolate
Work out the transition statesfor these on your own!
Base;TMSCl and/or
[3,3] [3,3]
The Ireland-Claisen Rearrangement: Use of Enolates to Generate Well-Defined Precursors
R. E. Ireland, R. H. Mueller, J. Am. Chem. Soc. 1972, 94, 5897.R. E. Ireland, R. H. Mueller, A. K. Willard, J. Am. Chem. Soc. 1976, 98, 2868.
O
OOHOTMS
O
OTMS
O
Key feature of chemistry is the ability to control enolate
geometry to then controlthe formation of either syn-
or anti- products
OH
O
OH
O
O
OH
O
OH
Z-enolate E-enolate
Work out the transition statesfor these on your own!
Base;TMSCl and/or
[3,3] [3,3]
The Ireland-Claisen Rearrangement: Use of Enolates to Generate Well-Defined Precursors
R. E. Ireland, R. H. Mueller, J. Am. Chem. Soc. 1972, 94, 5897.R. E. Ireland, R. H. Mueller, A. K. Willard, J. Am. Chem. Soc. 1976, 98, 2868.
O
O
OTMS
O
OTMS
O
Z-enolate
E-enolate
LDA, THF,-78 oC
O
LiN H
OR
H RO
LiN H
OR
R H
A1,2-strain 1,3-diaxial interaction
givesanti-
product
O
O
LDA, THFHMPA orDMPU,-78 oC
O
LiN H
OR
H RO
LiN H
OR
R H
1,3-diaxial interaction
givessyn-
product
A1,2-strain
or
or
The Ireland-Claisen Rearrangement: Use of Enolates to Generate Well-Defined Precursors
R. E. Ireland, R. H. Mueller, J. Am. Chem. Soc. 1972, 94, 5897.R. E. Ireland, R. H. Mueller, A. K. Willard, J. Am. Chem. Soc. 1976, 98, 2868.
O
O
OTMS
O
OTMS
O
Z-enolate
E-enolate
LDA, THF,-78 oC
O
LiN H
OR
H RO
LiN H
OR
R H
A1,2-strain 1,3-diaxial interaction[more favorable]
usually4:1 to 8:1
givesanti-
product
O
O
LDA, THFHMPA orDMPU,-78 oC
O
LiN H
OR
H RO
LiN H
OR
R H
1,3-diaxial interaction
givessyn-
product
A1,2-strain
or
or
The Ireland-Claisen Rearrangement: Use of Enolates to Generate Well-Defined Precursors
R. E. Ireland, R. H. Mueller, J. Am. Chem. Soc. 1972, 94, 5897.R. E. Ireland, R. H. Mueller, A. K. Willard, J. Am. Chem. Soc. 1976, 98, 2868.
O
O
OTMS
O
OTMS
O
Z-enolate
E-enolate
LDA, THF,-78 oC
O
LiN H
OR
H RO
LiN H
OR
R H
A1,2-strain 1,3-diaxial interaction[more favorable]
usually4:1 to 8:1
givesanti-
product
O
O
LDA, THFHMPA orDMPU,-78 oC
O
LiN H
OR
H RO
LiN H
OR
R H
1,3-diaxial interaction
givessyn-
product
A1,2-strain
or
or
The Ireland-Claisen Rearrangement: Use of Enolates to Generate Well-Defined Precursors
R. E. Ireland, R. H. Mueller, J. Am. Chem. Soc. 1972, 94, 5897.R. E. Ireland, R. H. Mueller, A. K. Willard, J. Am. Chem. Soc. 1976, 98, 2868.
O
O
OTMS
O
OTMS
O
Z-enolate
E-enolate
LDA, THF,-78 oC
O
LiN H
OR
H RO
LiN H
OR
R H
A1,2-strain 1,3-diaxial interaction[more favorable]
usually4:1 to 8:1
givesanti-
product
O
O
LDA, THFHMPA orDMPU,-78 oC
O
LiN H
OR
H RO
LiN H
OR
R H
1,3-diaxial interaction usually> 8:1
[decreasesdegree of
lithium coordination]
[now looser and preferred][could even be acyclic t.s.]
givessyn-
product
A1,2-strain
or
or
The Ireland-Claisen Rearrangement: Use of Enolates to Generate Well-Defined Precursors
R. E. Ireland, P. Wipf, J. D. Armstrong, J. Org. Chem. 1991, 56, 650.
O
OO
HO H
O
HO H
A: syn-product B: anti-product
Enolization conditions A B
LDA, 23% HMPA/THF
LDA, 45% DMPU/THF
LDA, THF
90
98
25
10
2
75
1. Enolization2. TBSCl; Δ3. NaOH, H2O
Remember: in cyclic systems boat-like transition states are possible. Here, the Z-enolate formed from the use of HMPA and DMPU likely goes through such a transition state. The
standard chair should be favored with the formation of the E-enolate.
and/or
The Ireland-Claisen Rearrangement: Applications in Complex Molecule Synthesis
R. E. Ireland, J. P. Vevert, J. Org. Chem. 1980, 45, 4259.
O
OHHO OH
HO OH
D-mannose O
OOMOM
O
O
OOMOM
OTMS
E-enolate
O
OOMOM
TMSO
boat t.s.
O
OMOM
H H
O
HOOH H
O
HO OH
(–)-nonactic acid
LDA,THF;
TMSCl
25 oC
[3,3]
The Ireland-Claisen Rearrangement: Applications in Complex Molecule Synthesis
R. E. Ireland, M. D. Varney, J. Org. Chem. 1986, 56, 635.
CO2H
OH
OO
Me
Me
H
OO
HO
(–)-chlorothricolide
OSEM
OMOM
OO
Me
Me
H
OO
MeOHO2C
O
OSEM
OMOM
OO
Me
Me
H
OO
MeOO
KHMDS,THF, HMPA;
TMSCl(50-72%)
[3,3]
The Ireland-Claisen Rearrangement: Applications in Complex Molecule Synthesis
M. Rowley, M. Tsukamoto, Y. Kishi, J. Am. Chem. Soc. 1989, 111, 2735.
THPO
OO
TBS
OBnTBSO
THPO
OOTBS OBn
TBSOxylene, Δ
[Brookrearrangement]
Z-enolate
(6:1 d.r.)
THPO
TBSO
OBn
OTBSO
O
O
HO
H
ophiobolin C
[3,3]
The Carroll Rearrangement: An Early Variant of the Claisen Reaction
M. F. Carroll, J. Am. Chem. Soc. 1940, 62, 704.
MeO
OO HO
base or acid,Δ
O
OOH
or O
OO
O
OOH
or O
OOO
[-CO2]
[3,3]
The Buchi-Claisen Rearrangement: A Method for the Preparation of Certain Cyclohexenes
G. Buchi, J. E. Powell, J. Am. Chem. Soc. 1970, 92, 3126.
OO
PPh3O
OO
O
Reaction process must proceed via a boat transition state
O O
low yield at best
O
Cis-oriented exocyclic olefins afford poor yields of productReaction temperatures are high
425 oC
sealed tube
O OO
major minor
[3,3]
425 oC
sealed tube
[3,3]
+Δ
[Diels-Alder]
and
The Buchi-Claisen Rearrangement: A Method for the Preparation of Certain Cyclohexenes
G. Buchi, J. E. Powell, J. Am. Chem. Soc. 1970, 92, 3126.
OO
PPh3O
OO
O
Reaction process must proceed via a boat transition state
O O
low yield at best
O
Cis-oriented exocyclic olefins afford poor yields of productReaction temperatures are high
425 oC
sealed tube
O OO
major minor
[3,3]
425 oC
sealed tube
[3,3]
+Δ
[Diels-Alder]
and
The Buchi-Claisen Rearrangement: A Method for the Preparation of Certain Cyclohexenes
G. Buchi, J. E. Powell, J. Am. Chem. Soc. 1970, 92, 3126.
OO
PPh3O
OO
O
Reaction process must proceed via a boat transition state
O O
low yield at best
O
Cis-oriented exocyclic olefins afford poor yields of productReaction temperatures are high
425 oC
sealed tube
O OO
major minor
[3,3]
425 oC
sealed tube
[3,3]
+Δ
[Diels-Alder]
and
A Modified Buchi-Claisen Rearrangement: Large Ring Synthesis
W. A. Kinney, M. J. Coghlan, L. A. Paquette, J. Am. Chem. Soc. 1984, 106, 6868.
O
O
H
O
H
Tebbereagent 200 oC
H
O
H
H
O
*
(38%)[3,3]
precapnelladiene
O
H
TL 1990, 31, 6799
The Danishefsky-Claisen Rearrangement: Combining the Virtues of the Buchi- and Ireland-Claisen Reactions
S. J. Danishefsky, R. L. Funk, J. F. Kerwin, J. Am. Chem. Soc. 1980, 102, 6889.
O O
OTBS OTBSR
O
R
OLDA,
TBSCl O
R
TBSOR R
O
TBSO105 oC
O
O
O
TBSO
O
HOLDA,
TBSCl 105 oC
toluene
toluene;HCl/H2O
[3,3]
[3,3]
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