Organic Chemistry

Reaction – Addition

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 Learning Outcomes

1. Given the information of the regiochemistry, stereochemistry and

reactants, predict the products of addition reaction
2. Given the information about the reactant and the substrate, predict
the outcome of addition reactions

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 References
• McMurry : various chapters
• Klein: Chapter 11

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 Outlines
• Regiochemistry & Stereochemistry in Addition reaction
• Adding H and H
• Adding H and X, Markovnikov
• Adding H and Br, anti-markovnikov
• Adding H and OH, markovnikov
• Adding H and OH, anti-markovnikov
• Adding Br and Br, adding Br and OH
• Adding OH and OH, Anti
• Adding OH and OH, syn
• Oxidative cleavage of an alkene

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 Addition Reaction
• Addition reactions are characterized by two
groups adding across an unsaturated bond

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 Regiochemistry in Addition Reaction
• Unsymmetrical Alkene

irrelevant
Br2

• Symmetrical alkene

irrelevant
Regiochemistry is only relevant when adding two different
groups across an unsymmetrical structure

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8
 Markovnikov’s Rule
1. Hydrogen rich carbon gets hydrogen richer
2. Hydrogen goes to the less substituted carbon
3. Nucleophile adds to a more substituted carbon

Markovnikov Anti-Markovnikov

2-chloro butane 1-chloro butane

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Why markovnikov product is the major product?
Carbocation stability principles

3° + H

H
+
2°

When an asymmetrical alkene undergoes electrophilic addition, the

product that predominates is the one that results from the more
stable of the two possible carbocation intermediates.

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Why markovnikov product is the major product?

Carbocation stability principles

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 Exercise

Less substituted

More substituted

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 Exercise
Predict the product of the following reaction:

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 Hydride shift
H+ OH
2° H2SO2

H2O
1°

OH
3° 1° H2SO2

H H2O
2°
H
OH
Correct product!!
Wrong !!!
If you have a 2° carbocation near
if you just apply
Markovnikov’s Rule 3° carbocation you will have
hydride shift
Hydride Shift and Methyl Shift Mechanism
[Link] 14
Stereochemistry in Addition Reaction

Top face syn addition Bottom face syn addition

Enantiomers

anti addition anti addition

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 Syn  same side of the plane  represent one pair of enantiomer
Anti  opposite side of the plane  another pair of enantiomer

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Stereoisomers and Addition Reactions

[Link]
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 Exercise

1. Anti-Makovnikov  OH goes to the least

substituted carbon

[Link] side stereochemistry

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 Exercise
Predict the product of the following reaction:

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 Case with no stereocenter
In all of the examples we have seen so far, we were creating two stereocenters:

Sometimes no stereocenters are being formed.

For example,

In situations like this, the stereochemistry is irrelevant. You will only get one product
(no stereoisomers).
 Case with only one stereocenter
Similarly, you may encounter situations where only one stereocenter is being
formed. For example,

In cases like this, the stereochemistry is still irrelevant. Why?

With only one stereocenter, there will only be two possible products (not four). These
two products will represent a pair of enantiomers (one will be R and the other will be
S). You will get both of these products

You can right away know that you will either get R and S

The stereochemistry is only relevant when the addition reaction

involves the creation of two new stereocenters.
Case with meso compound formed
should lead us to predict the following
products:

A meso compound

However, there are not two products here. Look closely and you will see that the two
drawings above are actually the same compound a meso compound
because it has an internal plane of symmetry.

In a case like this, there is actually only one product.

Check EXERCISE 11.21

we have now learned the basic terminology that you will need in order
to predict products of addition reactions

1. Which two groups are being added across the double bond (X and Y)?
2. What is the regiochemistry? (Markovnikov or anti-Markovnikov)
3. What is the stereochemistry? (syn or anti)

Note : With these three pieces of information, you should be able to

predict products with ease.

Now this information will not be given to you. Rather, you will have to
look at the reagents being used, and you will have to determine all
three pieces of information on your own.

The mechanism of each reaction contains all three pieces of information

that you need.

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 1. Adding H and H

• Hydrogenation

Regiochemistry is irrelevant
stereochemistry of hydrogenation reactions is relevant .

Catalytic Hydrogenation of Alkenes - Heterogeneous Catalysts

[Link]
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 Hydrogenation mechanism

Alkene coordinates with H is faced to the same sideofthe alkene

H-H bond is metal surface( atomic Therefore it is added to alkene at the
broken after hydrogen is much more same side
interaction with reactive than molec. Reaction Adding H and H
metal catalyst. H Hydrogen (H-H) (hydrogenation)
attached to Substrate alkene
surface. Reagent H2
Catalyst Metal (Pt, Pd or Ni)
Solvent -
Regiochemistry not relevant
Stereochemistry syn addition

Science - Addition reaction of alkenes

[Link]
Catalytic Hydrogenation of Alkenes - Heterogeneous Catalysts
[Link]
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 Exercise
Predict the product of the following reaction:

No enantiomer because we’re not creating

two new stereocenters

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 Exercise
Predict the product of the following reaction:

(Palladium)

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 2. Adding H and X, Markovnikov
• Adding hydrogen halide (HX) across an alkene

* Introduction to reaction mechanisms | Alkenes and Alkynes | Organic chemistry | Khan Academy( 11.21)
[Link]
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 Exercise
Draw the mechanism to this reaction:

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Exercise

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 Asymmetrical Alkene

Reaction Adding H and X

Substrate alkene
Reagent HX, where X can be Cl, Br, I

Catalyst -
Solvent -
Regiochemistry Markovnikov
Stereochemistry can be both syn and anti

Markovnikov's rule and carbocations

[Link]
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 Exercise
Predict the product of the following reaction:

Mechanism of reaction

Cl- Cl-
+
Exercise

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 3. Adding H and Br, Anti-Markovnikov
• Anti-markovnikov  only works with HBr in the
presences of peroxides (ROOR)
 The most common peroxide is hydrogen peroxide (H2O2)

Bromine is added to less substituted carbon

• The reaction involves a radical mechanism

Preference of forming the most stable radical

intermediate
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Radical stability
 Fates of radicals

Hydrogen abstraction: removing H from molecule

 The O - O bond of the
peroxide is easily broken to
form radicals in the presence
of light (hv)or heat.

Each of these RO radicals can

then abstract a hydrogen atom
from HBr, to form the reactive
intermediate (Br • )

Attack of less substituted

carbon by Br radicals

The carbon radical then

abstracts a hydrogen atom
from HBr
The whole Hydrogen atom (radical process).
The arrow is fish hook arrow to show radical process, meaning only one electron is moving

Alkene + HBR + ROOR - Reaction Mechanism

[Link]
 Exercise
Predict the product from the following reaction:

Bromine is added to less substituted carbon

We only have one stereocenter, therefore there will only be two possible
products whether the reaction was syn or anti

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 Exercise
Predict the product from the following reaction:

No chiral centers are created  stereochemistry irrelevant

Reaction Adding H and Br,

anti-markovnikov
Substrate alkene
Reagent HBr
Catalyst -
Solvent ROOR
Regiochemistry anti-Markovnikov
Stereochemistry can be both syn and
anti
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Determine which reagent are used for the following reaction

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 4. Adding H and OH, Markovnikov
• Hydration reaction
• Acid catalyzed

H3O+, or H+

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 Acid-catalyzed hydration mechanism

Protonation of
less substituted
carbon

Water acts as an Nucleophile and attacks the Intermediate

carbocation

This is the equilibrium reaction we can manipulate the reaction to go the direction that we want

Stereochemistry?
If only one stereocenter is formed,
then we expect a pair of
enantiomers (racemic mixture),

Elimination reaction

Addition of water (acid-catalyzed) mechanism | Organic chemistry | Khan Academy

[Link]
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Exercise
Exercise

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Reaction Adding H and OH,
markovnikov

Substrate alkene
Reagent H3O+
Catalyst -
Solvent -
Regiochemistry Markovnikov
Stereochemistry can be both syn and
anti

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 5. Adding H and OH, Anti-Markovnikov

BH3 : Borane  does not have an octet, it

Syn addition
has an empty p orbital and is very reactive
THF: tetrahydrofurane, stabilize BH3

Hydration reaction:

Be careful. The example above represents somewhat of an optical illusion. The products seem to suggest an
anti addition (the methyl and the OH are trans to each other). But think about what we added in this
reaction: we did not add OH and a methyl group.
The methyl group was already there. Rather, we added OH and H. The H that we added is not shown in the
product above (because it does not have to be drawn in a bond-line drawing). If you draw that H on the
compound above, you will see that it is on a dash—therefore, this was a syn addition of H and OH
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 Step 1-Hydroboration Reaction
This is a concerted process boron
and hydrogen are added
simultaneously

Pi bond attacks empty p orbital of boron and trigger a simultaneous hydride shift
BH2 is bigger/bulkier than H so it prefers the less substituted carbon (steric hindrance)  anti-
markovnikov
R group
The product shown above still has two remaining B-H bonds
(look at the BH2 group) and so the reaction can occur again with those B-H
bonds.
In other words, one molecule of BH3 can react with three molecules of alkene
to give a trialkylborane:

Hydroboration - Oxidation Reaction Mechanism formation of the trialkylborane

[Link] 46
 Step 2-Oxidation reaction
We formed trialkylborane previously Now, we move on to the next set of reagents,
which accomplish an oxidation reaction: H2O2 and hydroxide

1. a hydroxide ion can pull a proton off of hydrogen peroxide to form a hydroperoxide anion:

2. This hydroperoxide anion can attack the trialkylborane (remember that the boron atom still has an empty p orbital,

3. One of the alkyl groups migrates over (an alkyl shift) to kick off hydroxide:

Alkyl shift The net result is to place

oxygen in between B and R
his happens to all three B-R bonds:
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4. The final step involves removing the OR groups from B, which happens like this

RO- then grabs a proton from water, and

the final product is an alcohol.

Overall, we have a two-step synthesis for converting an alkene into an alcohol.

This two-step synthesis is called hydroboration-oxidation.

Reaction Adding H and OH,

anti-markovnikov
Substrate alkene
Reagent BH3+THF and H2O2 +
NaOH
Regiochemistry Anti-Markovnikov
Stereochemistry Syn
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Exercise

OH is added to the least substituted

carbon

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 6. Adding Br and Br; Adding Br and OH

Enantiomer

δ+

δ+

SN2-type process

*Halogenation | Alkenes and Alkynes | Organic chemistry | Khan Academy

[Link] 50
 A more substituted carbon is better
at handling the carbocationic
character

Halohydrin formation
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Reaction Adding Br and Br

Substrate alkene
Reagent Br2

Regiochemistry Not relevant

Stereochemistry Anti

Reaction Adding Br and OH

Substrate alkene
Reagent Br2

Solvent H2O

Regiochemistry OH goes to the more

substituted C
Stereochemistry Anti
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Exercise

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 7. Adding OH and OH, Anti
• To add two OH groups in an anti addition, we will employ a two-step synthesis:
• we will first make an epoxide, and then we will open the epoxide with water
• under conditions of acid-catalysis

Peroxy acid, strong oxidizing

agent albeit not very acidic

Meta-chloroperbenzoid acid
(MCPBA)

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• Peroxy acid reacts with alkene and form epoxide

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Reaction Adding OH and OH

Substrate alkene
Reagent MCPBA and H3O+

Regiochemistry Not relevant

Stereochemistry Anti

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Exercise

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 8. Adding OH and OH, Syn
• Also called syn hydroxylation
osmium tetroxide

osmium tetroxide (OsO4) adds across the same face

across the alkene in a concerted
Process both oxygen atoms
attach to the alkene simultaneously

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The syn addition of OH and OH can also be
accomplished using cold KMnO4 and hydroxide, i.e
NaOH

Reaction Adding OH and

OH
Substrate alkene
Reagent OsO44 and H2O2
or KMnO4 and
NaOH
Regiochemistry Not relevant
Stereochemistry syn
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Exercise

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9. Oxidative Cleavage of an Alkene

• Cleave the C=C bond

• Example: ozonolysis

Molozonide

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62
 Fill out the reagents needed for each of the transformations
What to inspects:
1. What is the substrate?
2. What has been added to the
substrate?
3. Is the product markovnikov or
anti markovnikov?
4. Is the addition syn or anti?

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 Summary
• Markovnikov and anti-markovnikov
• Syn and anti addition
• Adding H and H
• Adding H and X, Markovnikov
• Adding H and Br, anti-markovnikov
• Adding H and OH, markovnikov
• Adding H and OH, anti-markovnikov
• Adding Br and Br, adding Br and OH
• Adding OH and OH, Anti
• Adding OH and OH, syn
• Oxidative cleavage of an alkene
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• Markovnikov’s Rule vs Anti-Markovnikov in Alkene
Addition Reactions
• [Link]

• Markovnikov's Rule
• [Link]

• Syn and Anti Addition - Enantiomers, Meso

Compounds, Constitutional Isomers & Diastereomers
• [Link]

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