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Olefination Reactions
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Olefination Reactions
- Wittig Reaction (Phosphorous ylides)- Horner-Wadsworth-Emmons Reaction (Phosphonates)
- McMurry Coupling (Titanium complexes)
- Peterson Olefination (Silanes)
- Petasis / Tebbe Olefination (Carbene complexes)
- Julia-Lythgoe (Sulphones)Mechanism
Stereochemistry (Z / E)Experimental Examples
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Wittig Reaction
Olefination Reactions
X: Cl, Br, I, OTs
R3, R4: alkyl, aryl
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Wittig Reaction
Olefination Reactions
R1
X
H
PR´3
R1
PR´3
H
Base
R1
PR´3
H R1
PR´3
H
H
O
R2
R1
PR´3
H
H
O
R2
O PR´3
HR2
H R1
R1
PR´3
H
R2
O
H
O PR´3
HHR2 R1
R1
HR2
H R1
HH
R2
Rate limitating step
Z major E minor
betaines
oxaphophetane
(kinetic product)(thermod. product)
Mechanism:
1.Deprotonation
2.Coupling of the ylide to
the carbonyl compound(RL step) to form the
betaine
3.Cyclation to the
oxaphosphetane
4.Rearrangement to the
olefins
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Olefination Reactions
Stereochemistry:
1.the cis product isfavoured due to steric
inderance during the
attack of the carbonyl to
the ylide.
2.Non polar solvents andsalt free conditions induce
Z-olefin formation due to
the destabiliyation of the
betaines.
R1
X
H
PR´3
R1
PR´3
H
Base
R1
PR´3
H R1
PR´3
H
H
O
R2
R1
PR´3
H
H
O
R2
O PR´3
HR2
H R1
R1
PR´3
H
H
O
R2
O PR´3
HHR2 R1
R1
HR2
H R1
HH
R2
Rate limitating step
Z major E minor
betaines
oxaphophetane
(kinetic product)(thermod. product)
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Olefination Reactions
Preparation
Labile ylide Semistable ylide Stable ylide
Base used
Selectivity
In situ In situ isolated
nBuLi
NaNH2
KtBuO
NaEtO
Aq. NaOHNaOH
90% cis 90% transcis, trans
Stereochemistry:
1.the cis product isfavoured due to steric
inderance during the
attack of the carbonyl to
the ylide.
2.Non polar solvents andsalt free conditions induce
Z-olefin formation due to
the destabiliyation of the
betaines.
3.By increasing the
stability of the ylide, the
proportion of E-olefin
increases.
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Wittig Reaction
Olefination Reactions
Examples:
O
PPh3 CH2Wittig, 1950´s
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Olefination Reactions
X: Cl, Br, I, OTs
Schlosser Modification
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Schlosser Modification
Olefination Reactions
Example:
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Horner-Wadsworth-EmmonsReaction
Olefination Reactions
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Arbuzov Reaction
Olefination Reactions
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1. nucleophilic subs.
2. dealkylation
Mechanism
Olefination Reactions
R1 P(O)(OEt)2R1 X
X: Cl, Br, I
P(OEt)3
120-140 °C
Arbuzov Reaction
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Olefination Reactions
Example
Horner
I
I
I
I
Br
Br
I
I
(EtO)2(O)P
P(O)(OEt)2
I
I
(EtO)2(O)P
P(O)(OEt)2
I
I
R1
R1
R1
R1
R2
R2
KIO4, I2
H2SO4 / AcOH
NBS
hv
P(OEt)3
CHO
R1
KtBuO
CuI, PdCl2(PPh)3
R2
cruciforms
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Olefination ReactionsHorner
-111 10 9 8 7 6 5 4 3 2 1 0 ppm
I
I
OMe
OMe
OMeMeO
MeO OMe
B
A
C
C
B
A
D
D
Jtrans = 16 Hz.
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Still-Gennari modification:
R1 P(O)(OCH2CF3)2R2 H
O
R2
Z
R1
Olefination Reactions
KHMDS:
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Olefination Reactions
1. Deprotonation
(with KHMDS).
Mechanism
4. Rearrangement
2. Coupling with the
aldehyde and formation
of the betaine (unstable)
Still-Gennari
3. Evolution to the
oxaphosphetane
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Olefination Reactions
Example
Still-Gennari
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Peterson Olefination
Olefination Reactions
R2, R3: alkyl, arylR1: alkyl, aryl, ester, cyano, amide…
Highly versatile
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Olefination Reactions
Mechanism:
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Olefination Reactions
Example:
This is the only methodology to intruduce this (Z)‐alkene moiety
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Julia-Lythgoe Olefination
Olefination Reactions
X: Cl, Br, OCOR3
R1: H, alkyl, aryl
R2: H, alkyl, aryl, alkenyl
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Modified Julia-Lythgoe
Olefination Reactions
R1: H, alkyl, aryl
R2: H, alkyl, aryl, alkenylS
N
N
N
N
N
N
Ph
PYR PT BT
pyridin-2yl- benzothiazol-2yl-1-phenyl-1H-tetrazol
One‐pot
reaction
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Ol fi i R i
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Modified Julia-Lythgoe
Olefination Reactions
Example
N
N N
NO
2S
PhO
MeO
TESO
OHC
NaHMDS
HMPA
DME, -78 °C
TESO
O
MeO
(E)
35%
Ol fi ti R ti
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McMurry Coupling
Olefination Reactions
R: H, alkyl, aryl
Uncontrolled reaction. Random stereochemistry
Ol fi ti R ti
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McMurry Coupling
Olefination Reactions
O
K2
O
K2
TiCl3 K Ti2+ + KCl 2Cl-+
2KCl
O O
Ti
TiO2
1. Re-dox over the
carbonyl group.
2. Coupling of theradicals (Ti2+
mediated).
3. Rearrangement
with re-oxidationof Ti(II) to Ti(IV)
Mechanism
Ol fi ti R ti
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Exmaple
McMurry Coupling
Olefination Reactions
O
O TiCl3Zn-Cu
THF
Ol fi ti R ti
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Takai Olefination
Olefination Reactions
Ol fi ti R ti
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Takai Olefination
Olefination Reactions
R1 H
O
R1
R2R2CHX2
CrCl2R2
CrCl2
CrCl2H R2
CrCl2
R1 H
OCrCl2
E2
Complementary to
Wittig‐Stork
Olefination Reactions
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Takai Olefination
Olefination Reactions
Example
Olefination Reactions
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Tebbe/Petasis reaction
Olefination Reactions
Olefination Reactions
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Tebbe/Petasis reaction
Olefination Reactions
Olefination Reactions
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Tebbe/Petasis reaction
Olefination Reactions
Example: