Olefination Reactions

8/11/2019 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



Wittig Reaction


X: Cl, Br, I, OTs

R3, R4: alkyl, aryl



Wittig Reaction


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






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)




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.



Wittig Reaction


Examples:

O

PPh3 CH2Wittig, 1950´s




X: Cl, Br, I, OTs

Schlosser Modification





Schlosser Modification


Example:



Horner-Wadsworth-EmmonsReaction




Arbuzov Reaction




1. nucleophilic subs.

2. dealkylation

Mechanism


R1 P(O)(OEt)2R1 X

X: Cl, Br, I

P(OEt)3

120-140 °C

Arbuzov Reaction






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



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.



Still-Gennari modification:

R1 P(O)(OCH2CF3)2R2 H

O

R2

Z

R1


KHMDS:




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




Example

Still-Gennari



Peterson Olefination


R2, R3: alkyl, arylR1: alkyl, aryl, ester, cyano, amide…

Highly versatile






Mechanism:




Example:

This is the only methodology to intruduce this (Z)‐alkene moiety



Julia-Lythgoe Olefination


X: Cl, Br, OCOR3

R1: H, alkyl, aryl

R2: H, alkyl, aryl, alkenyl





Modified Julia-Lythgoe


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



Ol fi i R i



Modified Julia-Lythgoe


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



McMurry Coupling


R: H, alkyl, aryl

Uncontrolled reaction. Random stereochemistry

Ol fi ti R ti



McMurry Coupling


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



Exmaple

McMurry Coupling


O

O TiCl3Zn-Cu

THF

Ol fi ti R ti



Takai Olefination


Ol fi ti R ti



Takai Olefination


R1 H

O

R1

R2R2CHX2

CrCl2R2

CrCl2

CrCl2H R2

CrCl2

R1 H

OCrCl2

E2

Complementary to

Wittig‐Stork




Takai Olefination


Example




Tebbe/Petasis reaction












Example:

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Olefination Reactions

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