Organic Chemistry year 1 2011-2012

Professor Martin Wills

Email: [email protected] Office: C504

CONTENT OF LECTURES

• Substitution reactions at saturated carbon atoms: ‘SN2 and SN1’.

Mechanisms of substitution reactions, intermediates, orbital structures, implications
for stereochemistry, inversion and racemisation. Clayden et al, Chapter 17.

• Formation and reactions of alkenes: ‘E2 and E1’.

Methods for making alkenes, structure and selectivity. Reactions of alkenes with
electrophiles and nucleophiles. Oxidation and reduction reactions. Clayden et al.
Chapters 19 and 20.

Prof M Wills 1
 What you should know – what you will learn

What you should know by now: NOTE WE ARE GOING TO REVISE SOME OF THIS

- Hybridisation (sp, sp2, sp3) of carbon atoms.

- Orbital structure of C-C and C=C bonds.
- E/Z and R/S definition and how to assign configuration.
- Electronegativity and formal charge.
- Organic reaction mechanisms – ‘arrow pushing’.
- Factors which influence the stability of cations and anions.
- Free energy and reaction profiles.

What you will learn in this part of the course:

- The detailed mechanisms of substitution reactions at saturated carbon atoms

(SN2 and SN1 mechanisms).
-Factors which influence the mechanisms of substitution reactions.
-Methods for the formation of alkenes (E2 and E1 mechanisms ).
-Reactions of alkenes with electrophiles and nucleophiles.
-Reduction and oxidation reactions of alkenes.

Prof M Wills 2
 Nucleophilic substitution reactions – overview:
Why these reactions are important and some examples:

Substitution reaction: replacing one group with another one! Some examples:

Substitution at a saturated (sp3) carbon atom (M Wills section):

Br What about the
O + Br counterion?
O

3
Substitution at a saturated (sp ) carbon atom (M Wills section):

Br
N + HBr
H2N H

Substitution at an unsaturated (sp2) carbon atom (discussed in G. Challis section, term 2):

Br O

N + HBr
O H2N H

What mechanisms could there be for this reaction?

Can you define; the nucleophile, the electrophile, the leaving group.
Prof M Wills 3
 Substitution reactions – some definitions.

What is the significance of the ‘saturated carbon atom’.

What ‘shape’ do the
groups around this
3
sp hybridised carbon atom define?
Br
O + Br
H O
H

Which leaving groups can be used – what ‘drives’ the reaction?

Leaving group

X
O + X
H + O
H

Key point: Good leaving groups are halides (Cl, Br, I), OSO 2R, and other groups
which stabilise a negative charge.
Prof M Wills 4
 Mechanisms of substitutions reactions: SN2
There are two major mechanisms of substitution reactions.

The first is called the SN2 mechanism – Substitution, Nucleophilic, Bimolecular:

What do these three terms mean?

It is a single step mechanism; the nucleophilic adds and the leaving group is simultaneously
displaced in the same step. A concerted mechanism.
Br
H
H O H +
H Br
O

Rate = k [nBuBr][nPrO-]

What happens if I double the concentration of bromide? What if I double the concentration
of bromide and of propoxide?
Transition state

Bromide
Energy Ether (product)
(starting material)
Reaction co-ordinate.

Prof M Wills 5
 The transition state for SN2 reactions:
The SN2 mechanism – structure of the transition state.

What does this symbol mean?

 Br
Br H
H H + Br
H
H H O
O What ‘shape’ do the
 groups around this
atom define?
O

What is the hybridisation at this C atom? Nu: C C * antibonding orbital (empty

C C  bonding orbital (full)

Note partial bonds to nucleophile and leaving group. Nucleophile adds electron density to s* antibonding orbital.

*** Key point of nomenclature; it’s SN2 not SN2*** This is important ***

Prof M Wills 6
 Stereochemical consquences of SN2 reactions:

The SN2 mechanism – What happens at chiral centres:

S configuration:

R configuration
 Br
Br H
H Me + Br
H
Me Me O
O

O

Key concept – inversion of configuration.

*** Key point of nomenclature; INVERSION *** This is important ***

Prof M Wills 7
 Mechanisms of substitutions reactions: SN1
The second is called the SN1 mechanism – Substitution, Nucleophilic, Unimolecular:
What do these three terms mean?
It is a two step mechanism; the leaving group leaves in the first step to form a cationic
intermediate and then the nucleophile adds in the second step

INTERMEDIATE
cation
Br first step second step Me
Me Me
SLOW FAST Me Me
Me Me
Me O -H O
- Br H
O H
H
The first step is the rate-
determining step (rds)

Rate = k [C6H13Br] i.e. [nPrOH (nucleophile)] is not featured

What happens if I double the concentration of bromide? What if I double the concentration
of bromide and of alcohol?
First transition state
Second transition state

Cation
(intermediate)
Bromide
Energy Ether (product)
(starting material)

Prof M Wills 8
 Stereochemical consquences of SN1 reactions:

Br
HO HO
Me Me
Me or
Ph Ph Ph
- Br
S configuration:
Me
Ph O
R configuration S configuration:
O + Me
50% Ph 50%
A racemic product is formed.
(note - loss of proton not illustrated)

Why are there two products now?

What happened to the square brackets? Two enantiomers are formed in a 1:1 ratio
What is the ratio of the products? The cations are intermediates, not transition states.

*** Key point of nomenclature; RACEMISATION *** This is important ***

Prof M Wills 9
 Nucleophilic substitution reactions: Summary.

SN1 and SN2

The ‘1’ and ‘2’ refer to the molecularity of the reaction (the number of species in the rate
Expression).

SN1 is a two step reaction. SN2 is a one step reaction.

SN2 mechanisms go with inversion of configuration, S N1 with racemisation.

Make sure you understand the difference between an intermediate and a transition state.

Other substitution mechanisms include the SN2’ :

RNH Br
H RHN Me
Me
- Br

Prof M Wills 10
 Factors which influence SN2 and SN1 reactions:
‘If I do a substitution reaction, will it go through an S N2 or SN1 mechanism?’

i) Substrate structure. Steric hindrance and cation stability.

Unhindered substrate: Nu: = nucleophile
-
Br Will not form a stable cation if Br leaves:

H more likely to undergo SN2 H

H H
Nu:
Approach unhindered

Hindered (substituted) substrate

Br Will form very stable cation

Me more likely to undergo SN1

Me
Me
Nu: Approach hindered Me
by two large Me groups E2
Cation stability: Me Me H H Competes?
> > >
Me Me Me H Me H H H
tertiary secondary primary methyl cation

A primary halide is more likely to undergo SN2, a tertiary SN1. A secondary halide may do
both, although a good nucleophile would favour S N2 and a weak nucleophine SN1.
There are exceptions to all these guidelines.

Prof M Wills 11
 Other factors that increase cation stability.
Cation stability can also be increased by an adjacent double bond or aromatic ring:

H
H
H is more
Charge is delocalised stable than
into the aromatic ring H
or double bond.
benzyl cation

H
H
is more
H stable than
allyl cation H

However an adjacent benzyl or allyl group can also increase the rate of S N2 reactions, by
stabilising the transition state:


OMe
MeO + Br OMe H
via H
+ Br Br


Orbital overlap lowers the transition state

energy, and makes the reaction faster.

Prof M Wills 12
 Factors which influence SN2 and SN1 reactions cont:
ii) Effect of the solvent. This section has been expanded from the original circulation.
Solvent effects can be complex and a good summary can be found on p428-429 of Clayden et al.
Solvents which stabilise cations will tend to increase the rate of S N1 (because a ions are formed in the rate
determining step). These include dipolar aprotic solvents such as dimethylformamide (DMF) and dimethylsulfoxide
(DMSO) and dipolar protic solvents such as water or carboxylic acids. For S N2 reactions the situation is more
complex. A nonpolar solvent may speed up the reaction in a situation where the transition state is less polar than the
localised anions, and the product is neutral. In situations where a charged product is formed by the reaction of
neutral substrates, then a polar solvent such as DMF will be better because the transition state is more polar. Dipolar
aprotic solvents such as DMF can also make anionic nucleophiles more reactive in S N2 reactions because they
solvate the cation and make the anion ‘freer’ to react. Polar protic solvents (e.g. water, alcohols, carboxylic acids)
however can retard the rate of S N2 reactions by solvating the anion and making it less reactive.

iii) Effect of the nucleophile.

In general, more reactive nucleophiles favour the S N2 reaction. This is fairly logical.
Examples of 'reactive' Some relatively Examples of 'less reactive'
nucleophiles: stable anions are nucleophiles:
good nucleophiles e.g.
Alkoxides: RO Alcohols (not deprotonated) ROH
Anions of thiols R S
Amides: RNH Amines (not deprotonated) RNH2
Anions of phenols
O
Alkyl anions (for example Stabilised nucleophiles e.g. acetate:
so are neutral
Grignard (magnesium based)
phosphines O
reagents:
R3P
R (RMgBr) O

iv) Effect of the leaving group; good leaving groups are needed for both mechanisms.
Prof M Wills 13
 SN2 vs SN1 – all aspects must be considered:
(DMSO=Me2SO)
MeO K +
Br H H OMe INVERSION

i.e. good nucleophile, not very hindered substrate, good leaving group, hence SN2.

Ph H2O Ph Ph
+ RACEMIC

Br Me Me OH 50:50 HO Me

i.e. weak nucleophile, more hindered substrate, potential for stable cation, hence SN1.

What would be your prediction of a mechanism for:

Ph pyridine Ph
Cl + R OH O ? N
Ph Ph pyridine
Ph Ph Ph
Ph (mild base)
Ph H N
Ph O
Ph Ph Ph
Ph

Prof M Wills 14
 Formation and use of the OTs leaving group (very common
in synthesis):

OH O O (TsCl) O O
S S OTs
+ Cl O
H
H H
H H
H

O O O O
Et3N: S S
H O
O O +
(base)
H
H TsO

What is the mechanism, and why

go to all this trouble, i.e. why is OH
a poor leaving group? How else can it be
Made into a good leaving group?

Key point; Learn what a OTs (tosyl group) is – it will come up again!

Prof M Wills 15
 Alkenes– reminder of structure and formation:
Already discussed in Prof M. Shipman’s lectures:
In the case of a carbon atom attached to three other groups (by two single bonds and one double bond)
the single 2s and two 2p orbitals mix (rehybridise) to form three sp 2 orbitals. These are all arranged at
mutual 120 degree angles to each other and define a trigonal shape, the remaining p orbital projects out
of the plane of the three sp2 orbitals and overlaps with an identical orbital on an adjacent atom
to form the double bond:

2 x 2p on a carbon atom combine to form 3 x sp2 orbitals:

1 x 2s

which lie at mutual 120 degrees H

in a molecule such as etheneC2H6, H H H
whilst the remaining p orbital C C
H H
forms the double bond:
H H

The resulting structure is rigid and cannot rotate about the C=C bond without breakage of the
bond between the p-orbitals (the p bond). The can be separated into E and Z configuration isomers.

The p bond is much more reactive than the s bond – the bonds are not equivalent to each other.

Prof M Wills 16
 Alkynes – reminder of structure and formation:

In the case of a carbon atom attached to two other groups (by one single bonds and one triple bond)
the single 2s and one 2p orbitals mix (rehybridise) to form two sp orbitals. These are all arranged at
mutual 180 degree angles to each other and define a linear shape, the remaining p orbitals projecting out
from the sp orbital to overlap with identical orbitals on an adjacent atom to form the triple bond:

1 x 2s 1 x 2p on a carbon atom combine to form 2 x sp2 orbitals:

which lie at 180 degrees

in a molecule such as ethyneC2H4,
whilst the remaining p orbitals H H C C H
H
form the triple bond:

Both p bonds in an alkyne are much more reactive than the s bond.

Prof M Wills 17
 Alkenes – formation:

Most (but not all) alkene formation reactions involve an ELIMINATION reaction.

Alkyne reduction is also important (see later).

Br H Ph
H Ph
Ph Ph and/or
Ph Ph H
H - HBr
H H H
E-alkene Z-alkene

Recap on alkene structure.

Can you use the Cahn-Ingold-Prelog rules to determine the configuration?

Key point – H from one carbon atom and a leaving group (typically a halide) from the adjacent
carbon atom.

Prof M Wills 18
 Mechanisms for the formation of alkenes: E1 and E2:

Most elimination reactions, to form alkenes, involve an E2 or E1 elimination.

E2 = Elimination, bimolecular. It is a one-step reaction.

A strong base is needed - why is this?

H
Br H
Rate = k [Cyclohexylbromide][MeO-]
H H
MeO H
(This is a base)

Transition state

Bromide
Energy Alkene (product)
(starting material)
Reaction co-ordinate.

Prof M Wills 19
 E2 elimination – stereochemical implications: The ‘anti
periplanar’ requirement.
E2 reactions require correct orbital alignment in order to work. The optimal
arrangement is ‘anti periplanar’, where the ‘H’ and ‘Br’ (in an alkyl bromide) are anti to
each other.

Ph
Ph
can form a E- or Z-alkene upon elimination:
Br

Base:

H
H Ph H
Ph Ph Ph H
H Ph
H H Ph
Br
Base: E- alkene.

H
H H H
H Ph H H
Ph Ph Ph Ph Ph
Br
Z- alkene.

Which base would you use?

EtO-, HO-, alkoxide. Etc.
Prof M Wills 20
 E2 elimination – stereochemical implications: orbital
alignment:

Orbital alignment in E2 elimination reactions:

Substrate But O -
H tBuOH
H tBuOK
(base) Ph H
Ph H Ph H Ph H
Ph Ph Ph
H H H H Ph
Br Br - E- alkene.
Br
But O -
H tBuOH
H tBuOK
H H
H (base) H H H
H H
Ph Ph Ph
Ph Ph Ph Ph Ph
Br Br - Br Z- alkene.

The alignment of s and s* orbitals in the substrate leads to a smooth transition to a p bond in
the product. Which is the most likely product? The E, or trans, product.

Prof M Wills 21
 The E1 elimination mechanism:
E1 = Elimination, unimolecular. It is a two-step reaction.
It proceeds via a cationic intermediate.

Me
Me Me
Br

H H H
H -Br H
Et3N:

Rate = k [Methylcyclohexylbromide] Triethylamine (Et3N)

is a weak base.

Why does the substrate now have an extra methyl group?

Why was a weak base used in this reaction?

First transition state

Second transition state

Cation
(intermediate)
Bromide
Energy Alkene (product)
(starting material)

Reaction co-ordinate.
Prof M Wills 22
 Nature of the intermediate in an E1 reaction:
E1 reactions proceed through a ‘flat’, i.e. trigonal, cation (like S N1 reactions).

Me
Me Me
Br

H H H
H -Br H

sp2 carbon H
3
sp carbon
Me H

Sometimes multiple products are formed (irrespective of mechanism)–

What products would you predict from this reaction (more than one is possible)?

Me Me Me Me
Me
Me Me
Br Et3N (mild base)
and and
E1

Prof M Wills 23
 Formation of alkenes by elimination of alcohols:
See if you can write the mechanism for the following (E1) reaction:

Me
Me HCl (strong acid) H Me Me
HO MeOH (solvent) O
H
H H H
MeOH

Why is acid needed when the alcohol is the leaving group – why can’t we rely on a base?
What other alkene product can be formed, and how?

What would be the effect of using a base and an acid in the following? – write mechanisms.

HO H2SO4 Br KOtBu
? ?

K O

To be completed in lectures.

E1cb ‘conjugate base’ is less common mechanism, but important.

Prof M Wills 24
 Some alternatives to ‘simple’ elimination – the Wittig reaction:

The Wittig reaction is one of a number of reaction that provide a means for controlling where
the double bond ends up.

Ph3P CH2
O H2C
Phosphonium ylid
+ Ph3P O

the isomer, H3C

is not formed

This is how the ylid is formed:

base
PPh3 + CH3Br Ph3P CH3 Ph3P CH2 Ph3P CH2

Key point: this is important – learn it

Prof M Wills 25
 Some alternatives to ‘simple’ elimination – the Wittig reaction
(this is important – learn it)
Here is the mechanism of the Wittig reaction (you need to complete it).

O
O Ph3P
Ph3P C
C H2
H2

H2C
+ Ph3P O

Prof M Wills 26
 Substitution vs elimination, base vs nucleophile:
Sometimes a particular substrate can undergo a substitution or an elimination reaction.

The outcome depends on all the factors involved in the reaction;

The ‘is an alkoxide a nucleophile or a base?’ question. Answer - depends what it does:.

Br MeO Na MeO
Alkoxide is a nucleophile.

Br MeO Na Alkoxide is a base.

The most important factor is probably the substrate structure – deprotonation may outpace
nucleophilic addition when a substrate is very hindered. Certain substrates cannot undergo
elimination reactions.

Prof M Wills 27
 Reactions of alkenes with electrophilic reagents - bromine:

Alkenes are electron rich (in the p system) and react with electrophilic reagents:

Br
R Br2 R
R R
Br

The mechanism is as follows, the intermediate is a bromonium ion:

Br Br
R R
R R R
R
Br
Br Br Br

Br
Br
what about
trans
racemic

Prof M Wills 28
 Further additions of electrophiles to double bonds - HBr:

Hydrogen halides (HCl, HBr) also add across double bonds.

R Br
R R
R HBr
R R
R
R H

The mechanism involves the addition of a proton first (with the electron-rich alkene), then the
bromide. This is logical, because the alkene is electron rich.

R R Br
R R Br R R
R R R R

R R H H
H

Prof M Wills 29
 Regioselectivity of electrophilic additions to alkenes:
Addition of HCl and HBr (and other acids) across unsymmetric alkenes results in formation of the
more substituted halide (via the more substituted cation).

H H Br
H3C H H3C H
H3C HBr
H H H H
H
Br Major H Minor
H

The mechanism involves the addition of a proton first, as before, but in this case the unsymmetrical
intermediate has a larger density of positive charge at one end.

more stable BrH

cation H
H3C H3C H
H H H
H There are two
H H Br major options.
H3C
H Br
H Br The reaction goes via
H H H3C H3C H
the most stable (most
H H H substituted) cation.
H H H minor
less stable
cation

What about ?
Ph

Prof M Wills 30
 Acid catalysed hydration (addition of water) to alkenes:

Acid catalysed hydration (addition of water) is a very important reaction of alkenes:

H H OH
H3C H H3C H
H3C H2O
H H + H H
H +
H catalysis Major Minor
OH H
H

The mechanism involves the addition of a proton first, as before, followed by addition of water, the
regioselectivity is the same as for addition of HBr:

OH2
H H
H H
H3C H H H3C H H
H3C acid H3C H2O H H
H H regenera-
(H ) H O tion of H O
H H H H H
H

This mode of addition of H2O is referred to as ‘Markonikov’ selectivity (i.e. formation of the
MOST substituted alcohol via the MOST substituted cation.

Prof M Wills 31
 Radical reactions of alkenes: HBr in diethylether containing
peroxides.

HBr, peroxides in ether Br anti Markovnikov

H addition.

Mechanism (Clayden et al p 1033-1035)

RO OR 2 RO . (radical)

HO. HO.
H Br Br .

Br . Br
. .

Br
. H Br
Br
H + Br .

Prof M Wills 32
 Nucleophilic additions to C=C bonds – require nearby
electron withdrawing groups (‘ewg’).
The polar effects of C=O bonds can be transmitted through adjacent C=C bonds, e.g.

An enone: (a compound with a directly linked C=C and C=O double bond) can react with a
nucleophile at either the C of the C=O bond or at the C at the end of the C=C bond. This is called
conjugate addition, 1,4-addition and/or ‘Michael’ addition.

H H

H C O C O
H
C C C C
H R
H H
H H

R (a nucleophile)
Add acid at end
of reaction.

H
The oxygen atom drives the reaction- H
C O
it is more likely to gain a negative C C
R
charge because it is more H
H H
electronegative than adjacent atoms.

More on this from Prof Challis later in course.

Prof M Wills 33
 Polymerisation of alkenes/reactions of alkynes.
Alkenes/Alkynes

Another important reaction of alkenes is polymerisation, which is often radical-initiated:

CH3 CH3 CH3 CH3

H3C
n polymerisation

Alkynes are capable of many of the same reactions as alkenes, but twice if enough
reagent is used, e.g. addition of bromine:

Br
Br Br
Br2 Br2

Br Br
Br

More on polymerisation later in the course (Professor Haddleton).

Prof M Wills 34
 Cycloaddition reactions of alkenes: The Diels-Alder reaction.

Complete the diagram below:

note error corrected here

O O

+ O O

O O
a conjugated Alkene
diene (dienophile)

Reaction is concerted i.e. all bonds are formed and broken at the same time:

O O O

O O O

O O O

Stereochemistry: Bonds are formed on one face of the alkene, hence there is a high degree of stereocontrol.

Prof M Wills 35
 Alkene hydroboration reaction (important)!

Overall reaction (reagents to be added):

i) BH3
OH
ii) H2O2, NaOH

What happens if you carry out acid-catalysed hydration (addition of water).

OH
H , H2O

You get the secondary alcohol!

Prof M Wills 36
 Hydroboration mechanism – to be completed in lecture:
H
BH2 i) BH3
OH + B(OH)3
Concerted addition ii) H2O2, HO
of B-H bond across
the alkene - BH3
boron adds to least
hindered end: H2O
BH2
B
O
3

HO-O
BH
B
2 O
2
This is a migration HO-O
reaction
HO-O - OH
B B B
All the B-H bonds
are utilised. 3 2 2
Three alkenes add O
O
to one borane. OH

note there was an error on the handout -

should not be 'H' on 'B' at this stage.

Prof M Wills 37
 Reduction reactions of alkenes: and alkynes, stereochemistry
– formation of cis alkenes by hydrogenation.
First you need to make a substituted alkyne:

NH2 NaNH2 EtI i) NaNH2

H H H H
I ii)
Br
Why do you need to use NH2? Can you use EtO or Et3N?

These would not be powerful enough as bases.

This is the key reduction reaction:

H R1 R2
H
H2 (gas), Pd/C, quinoline
R1 R
2 H H
1 2
R R
or H2 (gas), Lindlar catalyst
catalyst surface

Why is the quinoline added to the catalyst? What happens if you do not add it?
You get reduction right down to the alkane.

The reduction takes place on a surface, and the hydrogen is transferred to one side
of the alkyne.
Prof M Wills 38
 trans Alkenes can also be formed from alkynes:

Na, NH3, then H

R1 R2

tBuOH is often used as a source of protons.

This is commonly known as ‘reducing metal’ reduction. It works by a mechanism in which

‘electrons’ are generated from the metal. Li, K and Mg are also sometimes used.

Here is the mechanism:

Na Na + e

2
e R NH3 H R2
1 2
R R .
1 .
R R1
Note this is a radical anion.
e

H R2 NH3 H 2
R H

R1 H R1 R1 R2

Prof M Wills 39
 Reduction of alkenes to alkanes – hydrogenation most commonly used:

Commonly used Commonly used

Metals: Pd, Rh, Ru, Ir, Supports: Carbon (graphite), silica

H H

H H
Stereochemistry:
note a
cis alkene is
formed

Relative rate of hydrogenation:

Me Me Me Me H Me H H

H Me H H H H H H
in general, more stable (more substituted) alkenes react more slowly.

slow reduction fast reduction

Why use a support to aid product separation, how does the reaction work?
Prof M Wills 40
 Hydrogenation of alkenes to make margarine:

Polyunsaturated fats are regarded as healthier than saturated ones but tend to be liquids so
They are partially hydrogenated to make margarine – solid but still with double bonds in..

Polyunsaturated vegetable oil.

CO2H o
Linolenic acid mp -11 C

H2 / Ni

CO2H Linoleic acid mp -5 oC

H2 / Ni

CO2H Oleic acid mp 16 oC

H2 / Ni

CO2H Stearic acid mp 71 oC

Fully saturated fatty acid.

Saturated fats have high melting points because they pack more efficiently.

Prof M Wills 41
 Alkene oxidation reactions:
Alkene oxidation reactions can give epoxides, diols, or even ketones from complete
cleavage of the alkene.

H R2 The  bond in alkenes

R1 H is very reactive.

peracid
O
R
O O OH HO OH 2
H R2 H R2 OsO4 H R

R1 H H osmium R1 H
R1 tetroxide
Epoxide diol
O3

H
+ R2
O O
R
1 H

What is the structure of ozone? Look it up Why might these products be useful?

Prof M Wills 42
 Epoxidation of alkenes using peracids:

This is mCPBA, O O
H H
(meta-chloroperbenzoic acid) Ar
which is a commonly used peracid O O O O
Cl

mCPBA mCPBA
O O
H H
Ar O Ar
H R
2
O O H R
2
H H H O H
O O
1 1
R H R H R1 R2 R1 R2
trans (E) alkene cis (Z) alkene

Learn the mechanism:

Ar
O
O
H H O R2
O

H R2 R1 H

R1 H

This is one of the best mechanisms!

Prof M Wills 43
 Ozonolysis of alkenes cleaves the double bond:

H R2 i) O3 H R2
+
O O
R 1
H ii) reducing agent 1
R H
(e.g. Zn metal, Ph3P, Me2S

reducing agent

O
O O O
H R
2 H O O R2
H R2
O
O
1
R H 1 H R1 O H
R
ozonide

Predict the products from:

O
i) O3

ii) reducing agent O

(e.g. Zn metal, Ph3P, Me2S
O
OMe i) O3 OMe

ii) reducing agent

O
(e.g. Zn metal, Ph3P, Me2S

Prof M Wills 44
 Alkene dihydroxylation:
Potassium permanganate (KMnO4)

O O 2 H2O OH
O O
Mn Mn
O O OH
O O
Mechanism should be
fairly easy to work out.
O O OH
O O 2 H2O
Os Os
O O OH
O O

What products are formed using

the following alkenes and OsO4?

i) OsO4 HO

ii) 2 H2O OH

OH
i) OsO4
OH
ii) 2 H2O

Note – OsO4 is expensive and very toxic. Better to use it catalytically (how would you do this?).

Prof M Wills 45
 The Wacker Oxidation:

ClPd Cl O
catalytic PdCl2, H2O, O2, CuCl2
1
1 R
R

keto-enol
tautomerism

Cl H HO
Pd HO PdCl
+ HPdCl
1
1 R
R
1 R
OH2

Pd + HCl

This is a commercial reaction used on a large scale in industry.

The CuCl2 and O2 reoxidise the PdCl2 (Pd is expensive).

Prof M Wills 46
 What you should understand and know:

• MECHANISM OF REACTIONS AT SATURATED CARBON ATOMS

The mechanisms and stereochemical implications of S N2 and SN1 reactions. Inversion
with SN2, racemisation with SN1. Factors which determine the likely pathway.
Alternative leaving groups. Examples of applications in synthesis.

• SYNTHESIS AND REACTIONS OF ALKENES (C=C)

E1 and E2 elimination mechanisms. Stereoselective alkene synthesis from alkynes
by hydrogenation and dissolving metal reduction; Wittig reaction including ylid
formation and mechanism; hydrogenation of alkenes; epoxidation, dihydroxylation and
ozonolysis of alkenes; hydration and hydroboration of alkenes; Wacker oxidation;
Diels-Alder cycloaddition.

Prof M Wills 47