1

Chapter 8
Addition reactions
Nucleophiles/Electrophiles
Regioselective/Stereoselective
Carbenes

Reactions of alkenes
Br

OSO3H

HBr
H2SO4

OH

H2O/H+
Br2

Br

Cl2
Cl
Br

Cl

For the reactions of HX with an alkene, the order of reactivity is HI> HBr> HCl> HF.
HCl is so slow to react (except to highly substituted alkeneWHY???) that a new
methodology has been developed to carry out these reactions. The hydrogen halide is
dissolved in alumina or silica along with the alkene in a solution of dichloromethane.
HF is so slow to react we can basically call it unreactive.

The pi bond of an alkene is a highly electron rich region, which can act as a nucleophile.
The alkene will attack an electrophile attaching the electrophile to the least substituted
carbon. This will leave a carbocation on the most substituted carbon, which will then
react with any available nucleophile. This is called Markovnikov addition after the
Russian chemist who came up with the addition. The most stable carbocation forms and
reacts with the nucleophile. Since it proceeds through a carbocation the product is
racemic. The mechanism is as follows:
H

Br

Br

Br

Know the energy diagram p. 333.

If you add HBr in the presence of peroxides you can get the anti-Markovnikov product to
form.
Br

HBr/Peroxides

The other addition reactions proceed through the same basic mechanism with the same
Markovnikov rules. In the hydration of the double bond, the reaction is similar to the
dehydration of an alcohol. In the dehydration reaction, concentrated acid and heat were
added to an alcohol to make an alkene. In the hydration reaction, dilute acid is added to
an alkene to make an alcohol. Because all of these reactions proceed through
carbocation, rearrangements are possible. Two modern reactions were created to avoid
the carbocation problem. Oxymercuration-demercuration gives us Markovnikov addition
without rearrangements. Hydroboration-oxidation gives us the anti-Markovnikov
addition without rearrangements.

OXYMERCURATION/DEMERCURATIONMARKOVNIKOV ADDITION
1) HgAcetate/THF/H2O
2) NaOH/NaBH4
OH
O

HgAcetate = Hg(OCCH3)2

OCCH3 = Ac

other steps

MECHANISM
O

HgOAc + OAc

Hg(OAc)2

HgOAc

H
O

O
O

+
HgOAc

HgOAc

Reaction is regio selective. The new group(OH) will always go to one carbon in
preference of another. Regioselective, reaction forms one regioisomer(by location) over
another.
The next reactions is regio stereoselective. Not only does the new group go to one
carbon in preference of another. It goes in a specific stereochemistry. Specifically syn
addition(same side).

HYDROBORATION/OXIDATIONANTI-MARKOVNIKOV/SYN ADDITION
OH

1) BH3:THF

2) H2O2/OH

MECHANISM
+ enatiomer

H
H

B
H

B
H

unstable
intermediate

R
B
R

OH

3
R
OR

repeat 2x's
B

RO

OR

OR
B

OR
RO

RO

OR

RO

OH

OH

O
R

OH

=
H

ROH

The addition of Br2 and Cl2 proceed through a slightly different mechanism from each
other and from the other addition mechanism. The Br2 mechanism is the important one to
us. This mechanism proceeds through a Bromonium(cyclopropane like) ion and leads to
anti addition. This reaction is stereospecific.
See mechanisms pages 350, 353 and 354
Br

BrBr
Br

Br

Br

BrBr
Br

This leads to a pair of trans(anti) enantiomers.

Note: The addition of Br2 to an unknown is a chemical test for the presence of
unsaturation. Br2 is a reddish-brown color to begin with. As it reacts with the
alkene/alkyne it becomes clear. This is a good test to see if your hydrogen
deficiency is due to rings or to unsaturation. Why must there be an excess of the
alkene/alkyne and not the Br2 .
Page 352. It may look like the reaction doesnt give anti product. But the bond has just
been rotated to show the meso structure more clearly.
Br

CH3
H

H3C
H

Br

CH3
Br

Br

H
CH3

These are the same.

They are just rotations
around the central
carbon-carbon bond.
They are called confomers

The bromonium ion is stereospecific as we see above. However it can also be

regiospecific. If you perform a halohydrin (Halogen and alcohol) reaction using BrOH,
the bromonium ion will form as in the Br2 reaction. Here however when the OH group
attacks in the anti (stereospecifically) conformation it also attacks with a high degree of
regioselectivity (attacking the more substituted carbon of the alkene). The reason for this
is the formation of a carbocation- like transition state. In that Transition State the
carbocation would prefer to be on the most substituted carbon.

OH

BrOH

Br

Here since one side of the double bond

is disubstituted and the other side is
monosubstituted, the OH will attach
only on the more substituted side.
Br

BrOH
OH

Here since both sides of the double bond

are monosubstituted, the OH will attach
equally on both sides.

OH

Br
Br

BrOH
Here the OH attaches only to the
more substituted side of the double bond.

O
H

The mechanism for the regiospecific Transition State is as follows:

OH-

BrOH

Br

OH

Br

Reactions of carbenes(diazomethane)
Carbenes are a group of compounds where the carbon has formed only 2 bonds. These
are extremely reactive intermediates. The reactions are highly stereospecific and are very
useful in forming hard to form cyclopropanes. Carbenes can readily form from
diazomethane or from chloroform. When forming dihalocarbenes there must be an
hydrogen but there can not be a hydrogen or elimination will occur instead.
H2C

or h

CH2 + N2
Highly reactive carbene.
K+

OK

+ CHCl3

OH

CCl 3

CCl2
Dihalocarbene
Highly reactive
Cl

OK + CHCl2CH2

OH

hydrogens lead to elimination

A carbene derivative called a carbenoid can be synthesized using the Simmons-Smith

cyclopropane synthesis. In this reaction diiodomethane and a Zinc-Copper couple are
stirred with an alkene to produce a reactive intermediate, the carbenoid, which forms a
cyclopropane ring with the alkene in situ.
Cl
Cl

Diazomethane

Br

Br

OK

CHCl3

CH2 I2/Zn(Cu)
Diethyl ether

Cl
Cl

Cl

Cl
Br
Br

This reaction produces a pair of enantiomer, what is the

other enantiomer for the diazomethane(for ex.)

Diol Addition to an Alkene

Syn hydroxylation(1,2-diols or glycols). There are two sets of reagents that lead to synhydroxylation. The first is potassium permanganate stirred cold in a basic water solution.
The seconds is osmium tetroxide and pyridine followed by aqueous acidic solution.
Although the osmium reagent is better, the potassium reagent is cheaper and much safer.
However, the potassium reagent often oxidizes the reaction too much and offers low
yields. The osmium reagent has been modified to allow catalytic amounts of osmium to
be introduced thus saving cost and offering less toxicity. Barry Sharpless of Stanfo rd is
one of the leading proponents of this method(Sharpless dihydroxylation) Who is Barry
Sharpless?
K M nO 4/O H - /H 2 O /cold

1) O sO 4, pyr idine

OH

OH

2) N aH S O 3 /H 2 O
W hat is the enantiom e r of this?
Is this a tr ue ster eospecific reaction?

CI S

TR ANS

OH

OH

OH

OH

OH

OH

OH

OH

KMnO4/OH-/H2O/cold

SHARPLESS
ASYMMETRIC
DIHYDROXYLATION

4 POSSIBLE ONLY PAIR ACTUAL

OH
OH

GIVES ONLY 1 ENANTIOMER OUT OF 4 POSSIBLE STEREOISOMERS

10

Oxidative Cleavage of Alkenes

Alkenes can be cleaved(cut in half) with reagents like hot potassium permanganate and
ozone. Hot potassium permanganate yields an oxidative workup that gives ketones, acids
and carbon dioxide.
1) KMnO4, OH-, H2O

heat
2) H 3O

+ CO 2

OH

O
-

1) KMnO4, OH , H2O
heat

O
H

+
2) H 3O+

HO

1) KMnO 4, OH- , H 2O
heat

HO
O

2) H3O

Note: The addition of hot potassium permanganate is a chemical test to find the
functionality of alkene groups in a molecule. The terminal carbon of a terminal
alkene is converted to carbon dioxide by hot potassium permanganate.
Monosubstituted carbons are converted to acids and disubstituted carbons are
converted to ketones.

11

O
e

1) KMnO4/OH-/H2O/heat

2) H+

c
d

OH

+ CO2

OH

a
b

O
g

terminal alkene leads to CO2

O
c

1) KMnO4/OH /H2O/heat

2) H

OH
O

OH
c
d

a
b

OH

internal alkene leads to acids and/or ketones

O

2
3

OH
O
c

1) KMnO4/OH /H2O/heat

2
1

2) H

b
O
3

1
2

c
d

a
b

OH

internal alkene leads to acids and/or ketones

O

2
1

OH

12

Ozone will also cleave a double bond. However ozone is followed by a reductive workup
that leaves ketone and aldehydes only.
O
o

1 ) O 3, C H 2C l2, - 7 8 C
2 ) Z n, A cO H

H
O

+
H

1 ) O 3, C H 2C l2, - 7 8 oC
2 ) Z n, A cO H

+
H

O
o

1 ) O 3 , C H 2 C l 2 , -7 8 C

H
O

2 ) Z n , AcO H

The reaction mechanism is fairly complicated. First an ozonide is formed. This collapses
and reforms in a new configuration. Finally Zinc as a Lewis Acid catalyzes a final
collapse of the intermediate to form the reductive product.

O
O
O

in itia l o z o n i d e

Z n /A c O H

O
O

H
O

o z o n id e r e fo r m s

13

Addition reactions with alkynes

HX and X2 reagents add to alkynes much like they do with alkanes. One of the big
differences between the two is that the alkynes can react twice with each reagent.
Therefore the final product could be an alkene or alkane. It could contain 2 or 4 halogens
depending on the reaction conditions. The additions occur in an anti/trans fashion. They
are regioselective and follow Markovnikovs Rule. The addition of HX to an alkyne will
stop at the alkene level if only one mole of reagent is used. You will not get a mixture of
products. See next page. Just like with alkenes, HBr is a little slow to react. A more
modern reagent is a combination of Acetyl Bromide(CH3COBr) with alumina. Also just
like alkenes, HBr with peroxides produces the anti-Markovnikov product. Alkynes can
be cleaved using ozonolysis or potassium permanganate.
1 mole HI
H
I

Br

1 mole B r 2

2 moles of
I2

2 mol es o f HC l

Br

Ac et yl B romide
Al umina

Cl

Cl

Br

Oxidative cleavage of alkynes leads to carboxylic acids.

1) O 3
2 ) A cO H
OH
H

Or
O

1) K M nO 4, O H
2) H +

HO

14

Br

HBr
OH

H 2O/H

H 2/Pt

Br

Br 2

HBr/H 2O 2

Br

1) I 2
2) 3 eq. NaNH 2
3) Pentyl chloride

Br
1

3
2

HBr

H2/Pt

HBr/H2O2

Br

Br

H2O/H+

OH

5
4

15

Chemical Reactions with Mechanisms

Reactions of alkenes
Br

OSO 3H

HBr
H 2 SO 4
H 2 O/H

OH
+

Br2

Br

Cl2
Cl
Br

Cl

Mechanism for addition of HX to alkene

H

Br

Br-

Br

Mechanism for addition of X2 to alkene.

Br

BrBr2

Br
Br

BrBr
Br

16

OXYMERCURATION/DEMERCURATIONMARKOVNIKOV ADDITION
1 ) H g A c et ate /T H F /H 2O
2 ) N aO H /N a B H

OH
O

H g A c et ate = H g ( O C C H 3 ) 2

OCCH

= Ac

o th e r s te p s

M E C H A N IS M
O

H gO Ac

H g (O A c )2

+ OAc
HgO Ac

H
O

H
O

+
HgOA c

HgOA c

HYDROBORATION/OXIDATIONANTI-MARKOVNIKOV/SYN ADDITION
OH

1 ) B H 3: T H F
H

2 ) H 2 O 2 /O H

M E C H A N IS M
+ en a ti o m er

H
H

B
H

u n s t ab l e
i n t er m e d i at e

O
B

OH

3
R
OR

rep e at 2 x 's
B

RO

OR

OR
B

OR
RO

RO

OR

RO

OH

OH

O
R

OH

=
H

ROH

17

Halohydrin reaction
OH

BrOH

Br

Mechanism for the reaction.

OH-

BrOH

Br

OH

Br

Ozonolysis of double bonds.

O
o

1) O3, CH2Cl2, -78 C

H

2) Zn, AcOH

Mechanism.
O

O
O
O
O
H

many steps

H
O

H
O
O

18

Chemical Reactions without Mechanisms

Addition reactions with alkynes
1 mole HI
H
I

Br

1 mole Br2

2 moles of
I2

2 moles of HCl

Br

Acetyl Bromide
Alumina

Cl

Cl

Br

Formation of a ketone
O

H 2O/HgSO 4
H 2SO4

Anti -Markovnikov addition of HBr.

Br

HBr/Peroxides

Carbene addition to alkene.

19

Cl
Cl

Diazomethane

Br

Br

OK

CHCl3

CH2I2/Zn(Cu)
Diethyl ether

Cl
Cl

Cl
Cl

Br
Br

This reaction produces a pair of enantiomer, what is the

other enantiomer for the diazomethane(for ex.)
Syn-dihydroxylation of alkene.
K M nO 4 /O H -/ H 2 O /cold

1) O s O 4 , pyridin e

OH

OH

2) N a H S O 3 /H 2 O
W ha t is th e en antio m er of thi s?
Is thi s a true s tereo spe c ific re ac tion?

Oxidation of alkene.

20

1) KMnO4, OH , H2O

+
CO 2
OH

heat
2) H 3O+

O
-

1) KMnO4, OH , H2O
heat

O
H

+
+

HO

2) H3O

1) KMnO4, OH-, H2O

HO
O

heat

2) H3 O

Oxidation of alkyne.

1) O3
2) AcOH
OH
H

Or
O

O
-

1) KMnO4, OH
2) H+

HO

21

Homework #4

Part I: Indicate if the following are (Markovnikov or anti-Markovnikov)

and/or (syn or anti addition).
1
HC l

Cl

HB r/ CC l 4

Br
Br

HB r/H 2 O 2
3
Br

Br 2 /H 2 O
4
OH

Br

B r2
5
Br

H 3O +
6
OH

1) HgA ce ta te , T HF , H 2 O
2) Na BH 4 , N aO H
OH

OH

1) B H 3 :T H F
8

2) H 2 O 2 , OH -

1) H g(O 2 CC F 3 ), C H 3 CH 2 C H 2 OH
2) N aB H 4 , Na OH
O CH 2 C H 2 C H 3

22

10
Diazomethane

CH2I2/Zn(Cu)/diethyl ether

11

KMnO4, OH -, H 2O, cold

12

OH
OH

1) OsO 4, pyridine
2) NaHSO3, H2O

13

OH
OH

Part II: Give the structures of the products

2m
ol
es

2 m o le s of
HC l

of

Br

C
1 ) K M n O 4 /O H -

H 2 O /he a t
2 ) H 3O

f
le o
o
1m

Cl 2

2 m o le s o f H B r

23

Part III: Give the structures of the products

B
C
Br2
H 2 O /H

1 ) K M n O 4/ O H

H 2 O /h e a t
2 ) H 3O

/H
Br 2

D ia z o m e th a n e

H B r /C C l 4

F
1 ) H g A c e ta te
T H F/H 2O
2 ) N a O H /N a B H 4

1 ) B H 3 :T H F
K M n O 4/ O H

2 ) H 2 O 2 /O H

H 2 O /c o l d

G
I
H
Part IV: Show mechanisms for the following.
Br

HBr/H2O2

HBr

Br

24

Part II:
Br

Cl

Br

Cl

Br

Br
O

OH

2 moles of
HCl

mo
les
o

fB

Cl

1) KM nO 4 /OH

H 2O/heat
2) H3 O

1m

o
o le

2 moles of HBr

fC

l2

Cl
Br

Br

25

Part III:
HO

O
2

Br
c

H2O/H

1) KMnO4/OH-

H2O/heat

OH
HO

Br

Br2

2) H3O

Br

/
Br 2

O
H2

4
5

2
3

Diazomethane

HBr/CCl4
Br

F
1) HgAcetate
THF/H2O
2) NaOH/NaBH4

1) BH3:THF
2) H2O2 /OHH

KMnO4/OHH2O/cold

G
I

HO

OH
OH

OH

26

Part IV: Show mechanisms for the following.

Br

HBr/H2 O2

Heat or h
H

HO

2 HO

Br

HOH + Br
H

Br

Br
H

Br

Br
3 0 radical better
o

than 2 radical.

Br

Br

BrH

27

Homework--Chapter 8

Name:

Draw the product for the following reactions.

HBr

HBr/H2O2

Br2/H2 O

1) Hg(O2 CCF3 ), butanol

2) NaBH4, NaOH

CH2I2/Zn(Cu), diethyl ether

KMnO4/OH-/H2O/cold

1) KMnO4/OH-/H2O/heat
2) H3O+

28

KEY
Draw the product for the following reactions.
Br

HBr

HBr/H2O2

OH

Br

Br2/H2 O

Br

1) Hg(O2 CCF3 ), butanol

2) NaBH4, NaOH

CH2I2/Zn(Cu), diethyl ether

KMnO4/OH-/H2O/cold
OH
OH

1) KMnO4/OH-/H2O/heat
2) H3O+
O O

HO