Transcript chapter8 - Department of Chemistry and Biochemistry

Chapter 8
Alkenes and Alkynes II:
Addition Reactions
Created by
Professor William Tam & Dr. Phillis Chang
Ch. 8 - 1
About The Authors
These PowerPoint Lecture Slides were created and prepared by Professor
William Tam and his wife, Dr. Phillis Chang.
Professor William Tam received his B.Sc. at the University of Hong Kong in
1990 and his Ph.D. at the University of Toronto (Canada) in 1995. He was an
NSERC postdoctoral fellow at the Imperial College (UK) and at Harvard
University (USA). He joined the Department of Chemistry at the University of
Guelph (Ontario, Canada) in 1998 and is currently a Full Professor and
Associate Chair in the department. Professor Tam has received several awards
in research and teaching, and according to Essential Science Indicators, he is
currently ranked as the Top 1% most cited Chemists worldwide. He has
published four books and over 80 scientific papers in top international journals
such as J. Am. Chem. Soc., Angew. Chem., Org. Lett., and J. Org. Chem.
Dr. Phillis Chang received her B.Sc. at New York University (USA) in 1994, her
M.Sc. and Ph.D. in 1997 and 2001 at the University of Guelph (Canada). She
lives in Guelph with her husband, William, and their son, Matthew.
Ch. 8 - 2
1. Addition Reactions of Alkenes
E
C
C
+ E
Nu
C
C
Nu
Ch. 8 - 3
1A. How To Understand Additions
to Alkenes

This is an addition reaction: E–Nu
added across the double bond
E
C
C
+ E
Nu
C
C
Nu
p-bond
s-bond
Bonds broken
2 s-bonds
Bonds formed
Ch. 8 - 4

Since p bonds are formed from the
overlapping of p orbitals, p electron
clouds are above and below the plane
of the double bond
C
C
p electron
clouds
Ch. 8 - 5

Electrophilic
● electron seeking
● C=C and C≡C p bonds are
particularly susceptible to
electrophilic reagents (electrophiles)

Common electrophile
● H+, X+ (X = Cl, Br, I), Hg2+, etc.
Ch. 8 - 6

In an electrophilic addition, the p
electrons seek an electrophile, breaking
the p bond, forming a s bond and
leaving a positive charge on the vacant
p orbital on the adjacent carbon.
–
Addition of B to form a s bond
provides an addition product
Ch. 8 - 7

C
C

E


Nu
E
C
C
+ Nu
Nu E
C
C
Ch. 8 - 8
2. Electrophilic Addition of
Hydrogen Halides to Alkenes:
Mechanism and Markovnikov’s
Rule

C
Mechanism
C

E

Nu
A
C
C
Nu
Nu E
C
C
Ch. 8 - 9

Mechanism
● Sometimes do not go through a
“free carbocation”, may go via
E
C
C
Ch. 8 - 10

Markovnikov’s Rule
● For symmetrical substrates, no
problem for regiochemistry
H
H
C
H
C
E
Nu
E
H
H
C
C
H
H
same
H as H
E
C
C
H
H
H
Nu
H
E
Nu
C
C
H
H
same
H as H
Nu E
C
C
H
H
H
Ch. 8 - 11

Markovnikov’s Rule
● But for unsymmetrical substrates,
two regioisomers are possible
H
H3C
C
H
C
E
Nu
E
E
CH3
H
C
C
H
H
H
or
CH3
C
C
H
H
Nu
Nu
CH3
E
Nu
C
C
H
H
H
different
H from CH3
Nu E
C
C
H
H
H
Ch. 8 - 12

Markovnikov’s Rule
● In the electrophilic addition of an
unsymmetrical electrophile across a
double bond of an alkene, the more
highly substituted and more
stabilized carbocation is formed as
the intermediate in preference to
the less highly substituted and less
stable one
Ch. 8 - 13

Markovnikov’s Rule
● Thus


E

Nu
E
Nu
E
o
o
E
NOT
o
Note: carbocation stability  3 > 2 > 1
Ch. 8 - 14

Addition of Hydrogen Halides
● Addition of HCl, HBr and HI across
a C=C bond
+
● H is the electrophile


+ H


Br
slow
Br
r.d.s
fast
Br
Br
NO
Ch. 8 - 15
Ch. 8 - 16
2A. Theoretical Explanation of
Markovnikov’s Rule
H3C
H
C
H

C
H
 
H X
step 1
(slow
r.d.s.)
H
CH3
C
C
H
H or CH3
C
C
H
H H
2o carbocation
H H
1o carbocation
(more stable)
(more stable)
One way to state Markovnikov’s rule is to
say that in the addition of HX to an alkene,
the hydrogen atom adds to the carbon atom
of the double bond that already has the
greater number of hydrogen atoms
Ch. 8 - 17
☓
H
H
Br
(1o cation) fast
H
(minor)
Br
Br
slow
(r.d.s.)
H
Br
(2o cation) fast
Step 1
H
Step 2
Br
(major)
Ch. 8 - 18
Ch. 8 - 19

(1)
Examples
H
Cl
Cl
H
+
H
(95
(2)
H
Cl
:
5)
H
Br
Br
+
Br
(98
H
:
2)
Ch. 8 - 20
2B. Modern Statement of
Markovnikov’s Rule

In the ionic addition of an
unsymmetrical reagent to a double
bond, the positive portion of the added
reagent attaches itself to a carbon
atom of the double bond so as to yield
the more stable carbocation as an
intermediate
Ch. 8 - 21

Examples
OH
OH
Cl
(1)
 
Cl OH
Cl
more stable
(major)
3o cation
Cl
OH
Cl
OH
less stable
1o cation
(minor)
Ch. 8 - 22

Examples
Cl
I

(2)

I


Cl
I
Cl
(major)
more stable
3o cation
Cl
I
less stable
1o cation
Cl
I
(minor)
Ch. 8 - 23
2C. Regioselective Reactions

When a reaction that can potentially yield
two or more constitutional isomers actually
produces only one (or a predominance of
one), the reaction is said to be
regioselective
H
Cl
Cl
H
+
(major)
H
Cl
(minor)
regioisomers
Regioselectivity:
95
:
5
Ch. 8 - 24
2D. An Exception to Markovnikov’s Rule
H
Br
Br
RO OR
heat
(anti-Markovnikov's
product)
H

Via a radical mechanism (see Chapter 10)

This anti-Markovnikov addition does not
take place with HI, HCl, and HF, even when
peroxides are present
Ch. 8 - 25
3. Stereochemistry of the Ionic
Addition to an Alkene
H
C
Bu
C
H
H
X
H
Bu
C
H
CH2
H
C
CH3
Bu
(S)-2-Halohexane
(50%)
achiral
trigonal planar
carbocation
Bu
X
attack from bottom
racemate
attack from top
H
X
X
H
C
CH3
X
(R)-2-Halohexane
(50%)
Ch. 8 - 26
4. Addition of Sulfuric Acid to Alkenes
OSO3H
conc. H2SO4
cold
O
HO
S
H
 
O H
OSO3H
O
H
more stable
o
3 cation

Addition of H–OSO3H
across a C=C bond
H
less stable
o
1 cation
Ch. 8 - 27
4A. Alcohols from Alkyl Hydrogen
Sulfates
conc. H2SO4
cold

OSO3H
H
H2O
OH
heat
H
The overall result of the addition of
sulfuric acid to an alkene followed by
hydrolysis is the Markovnikov addition
of H– and –OH
Ch. 8 - 28
5. Addition of Water to Alkenes:
Acid-Catalyzed Hydration

Overall process
● Addition of H–OH across a C=C
bond
+
● H is the electrophile
● Follow Markovnikov’s rule
H2O
dilute H3O+
(e.g. dilute H2SO4, H3PO4)
OH
H
Ch. 8 - 29
5A. Mechanism
H
H
O
H2O
H
slow
H
H
fast
(step 2)
(step 1)
H
more stable
O
H
3o cation
fast
(step 3)
H2O
H
H
O
H
H
+
OH
Ch. 8 - 30
5B. Rearrangements

Rearrangement can occur with certain
carbocations
H2O
H
H2SO4
1,2-alkyl shift
NOT
OH
OH
(major product)
H2O
Ch. 8 - 31
6.

Alcohols from Alkenes through
Oxymercuration–Demercuration:
Markovnikov Addition
Step 1: Oxymercuration
C

C
Hg(OAc)2
THF-H2O
C
HO
C
HgOAc
Step 2: Demercuration
C
HO
C
HgOAc
NaBH4
OH
C
HO
C
HCh. 8 - 32
6A. Regioselectivity of Oxymercuration–Demercuration

Oxymercuration–demercuration is also
highly regioselective and follows
Markovnikov’s rule
HgOAc
Hg(OAc)2
THF-H2O
NaBH4

HO
OH
H
HO
Ch. 8 - 33
6B. Rearrangements Seldom Occur in
Oxymercuration–Demercuration

Recall: acid-catalyzed hydration of
some alkenes leads to rearrangement
products
e.g.
H2O
H2SO4
OH
H
Ch. 8 - 34
H2O
H2SO4
H
1,2-alkyl shift
H
O
H
H
H2O
H
H2O
OH
H
Ch. 8 - 35

Rearrangements of the carbon skeleton
seldom occur in oxymercuration–
demercuration
no rearrangement
OH
1. Hg(OAc)2, THF-H2O
2. NaBH4
via
H
OH
Hg(OAc)
Ch. 8 - 36
6C. Mechanism of Oxymercuration

Does not undergo a “free carbocation”

OAc
Hg
OAc

HgOAc
AcO + 
H2O
HgOAc
HO
HgOAc
H2O
O
H
H
Ch. 8 - 37

Stereochemistry
● Usually anti-addition

Hg(OAc)2
H3C
H
THF-H2O
H2O
H3C
Hg(OAc)

OH
H
CH3
Hg(OAc)
Ch. 8 - 38
Although attack by water on the
bridged mercurinium ion leads to anti
addition of the hydroxyl and mercury
groups, the reaction that replaces
mercury with hydrogen is not
stereocontrolled (it likely involves
radicals). This step scrambles the
overall stereochemistry
 The net result of oxymercuration–
demercuration is a mixture of syn and
anti addition of –H and –OH to the
alkene
Ch. 8 - 39


Solvomercuration-Demercuration
Hg(O2CCF3)2
OR
THF-ROH
Hg(O2CCF3)
NaBH4
OH
OR
H
Ch. 8 - 40
7.
Alcohols from Alkenes through
Hydroboration–Oxidation:
Anti-Markovnikov Syn Hydration
C

C
"BH 3"
C
C
H
BH2
Addition of H–BH2 across a C=C bond
Ch. 8 - 41

BH3 exists as dimer B2H6 or complex
with coordinative solvent
H
H
H
B
B
H
H
H
H
H
B
H
O
H
(BH3-THF)
H
B
Me
S
H
Me
(BH3-DMS)
Ch. 8 - 42
syn addition
1. BH3-THF
H
OH
CH3
H

H3C
H
2. H2O2, OH
Anti-Markovnikov addition
of “H” & “OH”
Ch. 8 - 43

Compare with oxymercurationdemercuration
Hg(OAc)2
H3C
H
THF-H2O
OH
H
CH3
Hg(OAc)
NaBH4
anti addition
Markovnikov addition
of “H” & “OH”
OH
H
CH3
H
Ch. 8 - 44
8. Hydroboration: Synthesis of
Alkylboranes
C
C
alkene
+H
B
boron
hydride
hydroboration
C
C
H
B
alkylborane
Ch. 8 - 45
8A. Mechanism of Hydroboration
H3C
H
H
H
H3C
H
+
B
H3C
H
H
H
H
H
H
B
H
H3C
H
H
H
H
H
B
H
H
p complex
H
H
H
B
syn addition
H
of H and B
H3C 
H 
H
H
four-atom
concerted T.S.
H
H
B

H
H
H
Ch. 8 - 46

(1)
Other examples
H
BH2-THF
+
H
BH2
H2B
(99
(2)
H
BH2-THF
:
H
1)
+
H
BH2
(98
H2B
:
H
2)
Ch. 8 - 47
8B. Stereochemistry of Hydroboration

Syn addition
H3C
H
BH3-THF
H
BH2
CH3
H
Ch. 8 - 48
9. Oxidation and Hydrolysis of
Alkylboranes

H
H
H
H
BH2
H
B
B always ends
up on the least
hindered carbon
B

B
B
H
(trialkyl borane)
H
Ch. 8 - 49

Oxidation
B
O
H2O2
O
B
O
Ch. 8 - 50
● Via
R
R
R3B
O
OH
R
B
O
OH
R
R
HO
R
O
RO
B
R
OR
R
O
HO
B
OR
R
B
O
OR
B
OR
O
OH
OH
OR
OR
RO
B
OR
Ch. 8 - 51

Hydrolysis
O
O
B
O
NaOH
H2O
3
OH
+ Na3BO3
Ch. 8 - 52

Overall synthetic process of
hydroboration-oxidation-hydrolysis
1. BH3-THF
2. H2O2
3. NaOH, H2O
H
OH
● Overall: anti-Markovnikov addition
of H–OH across a C=C bond
● Opposite regioisomers as
oxymercuration-demercuration
Ch. 8 - 53

anti-Markovnikov
syn addition
Example
BH3-THF
H3C
H
H
OH
CH3
H
H
BH2
CH3
H
H2O2
OH
This oxidation step occurs with
retention of configuration
Ch. 8 - 54
10. Summary of Alkene Hydration
Methods
Summary of Methods for Converting Alkene to Alcohol
Reaction
Regiochemistry
Stereochemistry
Occurrence of
Rearrangements
Acid-catalyzed
hydration
Markovnikov
addition
Not controlled
Frequent
Oxymercurationdemercuration
Markovnikov
addition
Not controlled
Seldom
Hydroborationoxidation
Anti-Markovnikov Stereospecific:
addition
syn addition of
H – and –OH
Seldom
Ch. 8 - 55

Examples
via
H
H
H
OH
H
H2O
1,2-hydride
shift
with
rearrangement
OH
1. Hg(OAc)2, THF-H2O
H
2. NaBH4, OH
Markovnikov addition of H2O
without rearrangement
H
1. BH3-THF
2. H2O2, OH
anti-MarkovniOH kov, syn
addition of H2O
Ch. 8 - 56
11. Protonolysis of Alkylboranes
R
B
alkylborane


CH3CO2H
heat
R
H + CH3CO2
B
alkane
Protonolysis of an alkylborane takes place
with retention of configuration; hydrogen
replaces boron where it stands in the
alkylborane
Overall stereochemistry of hydroboration–
protonolysis: syn
Ch. 8 - 57

e.g.
1. BH3-THF
2. CH3CO2D
H
H3C
H3C
H
H D
+ enantiomer
via
H3C
H
H
BH2
Ch. 8 - 58
12. Electrophilic Addition of Bromine
and Chlorine to Alkenes

Addition of X–X (X = Cl, Br) across a
C=C bond
C
C
Br2
CCl4
Br
C
C
Br
(vicinal
dibromide)
Ch. 8 - 59

Examples
(1)
Br
Br2
Br
+
o
5 C
Br
(anti addition of Br2)
Br
(racemate)
Cl
(2) Ph
Cl2
Ph
10oC
2
Ph
(anti addition of Cl2)
1
Ph
Cl
Ph
Ph
Cl
Cl
same as
(rotation of C1-C2 bond)
Ch. 8 - 60
12A. Mechanism of Halogen Addition
C
C
+
Br
Br
C
Br–Br bond becomes
polarized when close
to alkene
C
 Br
 Br
Br
+ Br
Br
(vincinal
Dibromide)
Br
(bromonium)
Ch. 8 - 61

Stereochemistry
● Anti addition
Br
H
Br
Br
CCl4
H
Br
H
Br
Br
H
SN2 reaction
enantiomer +
(anti)
Ch. 8 - 62
13. Stereospecific Reactions

A reaction is stereospecific when a
particular stereoisomeric form of the
starting material reacts by a
mechanism that gives a specific
stereoisomeric form of the product
Ch. 8 - 63
● Reaction 1
H
H3C
CH3
H
Br2
CCl4
CH3
C H
Br
H C
H3C
trans-2-Butene
Br
Br
Br
H
H3C
H
CH3
(2R,3S)-2,3-Dibromobutane
(a meso compound)
● Reaction 2
H
H3C
H
CH3
cis-2-Butene
H
H
Br2
Br
CCl4
H
H3C
C
CH3 + H3C
C
Br
(2R,3R)
Br
C
C
Br
H
CH3
(2S,3S)
(a pair of enantiomers)
Ch. 8 - 64

Addition of bromine to cis-2-Butene
(a)
(a)
H
H3C
C


C
H
CH3
Br
Br
H3C
Br
(b)
H
H
C
C
H
Br
C
CH3
C
H
Br
H3C
(2R,3R)-2,3-Dibromobutane
(chiral)
CH3
Br
bromonium
ion
(achiral)
H
H3C
C
Br
C
H
Br
CH3
(2S,3S)-2,3-Dibromobutane
(chiral)
(b)
Ch. 8 - 65

Addition of bromine to trans-2-Butene
(a)
(a)
H
H 3C
C


C
CH3
H
Br
Br
H3C
Br
H
(b)
CH3
C H
C
CH3
C H
Br
H C
Br
H3C
(R,S)-2,3-Dibromobutane
(meso)
Br
bromonium
ion
(b)
(achiral)
H
H3C
C
Br
C
CH3
Br
H
(R,S)-2,3-Dibromobutane
(meso)
Ch. 8 - 66
14. Halohydrin Formation
C
C
X2
H2O
OH
C
C
X
Addition of –OH and –X (X = Cl, Br)
across a C=C bond
+
 X is the electrophile
 Follow Markovnikov’s rule

Ch. 8 - 67

Mechanism
Br
H3C
H
H2O

Br
H2O
H3C
Br

H3C
Br
H
OH
H
CH3
Br
Ch. 8 - 68

Other variation
● If H2O is replaced by ROH, RÖH will
be the nucleophile
e.g.
Br2
MeOH
OMe
Br
Ch. 8 - 69
15. Divalent Carbon Compounds:
Carbenes
15A. Structure and Reactions of
Methylene
CH2
N
N
Diazomethane
heat
or light
CH2
+
Methylene
(a carbene)
N
N
Nitrogen
Ch. 8 - 70
CH2
N
N
H2C
N
N
CH2
II
I
C
C
+
CH2
N
N
III
C
C
C
Alkene
Methylene
H
H
Cyclopropane
Ch. 8 - 71
15B. Reactions of Other Carbenes:
Dihalocarbenes
:CX2 (e.g. :CCl2)
 Generation by a-elimination of
chloroform

H
Cl
C
Cl
OtBu
Cl
t
+
CCl2
BuOH + Cl
Ch. 8 - 72

Usually a syn (cis) addition across a
C=C bond
t
H
BuOK
Cl
CHCl3
H
Cl
(a cyclopropane)
Ch. 8 - 73

Stereospecific reactions
CCl2
CCl2
Cl
Cl
Cl
Cl
Ch. 8 - 74
15C. Carbenoids: The Simmons-Smith
Cyclopropane Synthesis
CH2I2
+
Zn(Cu)
(Zinc-copper
couple)
I
ZnI
C
H2
(a carbenoid)
Ch. 8 - 75

A stereospecific syn (cis) addition
across a C=C bond
CH2I2
Zn(Cu)
(trans)
(trans)
CH2I2
Zn(Cu)
(cis)
(cis)
Ch. 8 - 76
16. Oxidation of Alkenes:
Syn 1,2-Dihydroxylation

Overall: addition of 2 OH groups across
a C=C bond
C
C
OH OH

⊖
Reagents: dilute KMnO4 / OH / H2O /
cold or OsO4, pyridine then NaHSO3,
H2O
Ch. 8 - 77
16A. Mechanism for Syn
Dihydroxylation of Alkenes
dil. KMnO4
OH, H2O
cold
C
C
O
O
Mn
O
C
OH
H2O
O
OsO4
pyridine
C
O
O
O
Os
NaHSO3
H2O
O
C
OH OH
+ MnO2
C
C
C
C
C
OH OH
+ Os
Ch. 8 - 78

Both reagents give syn dihydroxylation
dil. KMnO4

OH , H2O, cold
H
H
H
H
or OsO4, pyridine
then NaHSO3
OH
OH
(cis-diol)
Ch. 8 - 79

Comparison of the two reagents
● KMnO4: usually lower yield and
possibly side products due to overoxidation
1. KMnO4, 
+
2. H
OH
O
+ O
(oxidative cleavage of C=C)
OH
● OsO4: usually much higher yield but
OsO4 is extremely toxic
Ch. 8 - 80
17. Oxidative Cleavage of Alkenes
17A. Cleavage with Hot Basic
Potassium Permanganate
b

a
a
b
b
KMnO4, OH , H2O

2
a O
b
H3O
or
a
O
a
b
O
2
b
a OH
Ch. 8 - 81

(1)
Other examples
1. KMnO4, OH, H2O, heat
2. H3O
O

+
O
(2)
1. KMnO4, OH, H2O, heat
2. H3O
C
O
O
O
OH
Ch. 8 - 82
17B. Cleavage with Ozone
R
R'
R"
H
1. O3
2. Zn, AcOH
or Me2S
R
R"
O + O
R'
H
Ch. 8 - 83

(1)
Examples
O
1. O3
2. Zn, AcOH
O
(2)
O
1. O3
2. Me2S
+
H
O
Ch. 8 - 84
Mechanism

C
C
C
O
O
C
O
O
C
O
C
O
O
+
C
O
O
initial ozonide
O
C
O
O
C
O
O
Zn(OAc)2 +
C
O
ozonide
C
O + O
C
Ch. 8 - 85
18. Electrophilic Addition of
Bromine & Chlorine to Alkynes
R
R
C
C
C
C
H
H
X2
X2 (excess)
CH2Cl2
(X = Cl, Br, I)
X
H
C
H
C
X2
X
(anti-addition)
R
R
X
X
C
C
X
X
X
X
C
C
X
X
H
H
Ch. 8 - 86
19. Addition of Hydrogen Halides
to Alkynes
R

H3C
C
C
H
H
X (excess)
R
(X = Cl, Br, I)
Regioselectivity
● Follow Markovnikov’s rule
C
C
H
HBr
Br
H
C
CH3
C
H
HBr
X
H
C
C
X
H
H
Br H
CH3
C
C
H
Br H
gem-dibromide
Ch. 8 - 87

Mechanism
CH3
C
C
H
H
Br
H
CH3
C
Br
C
H
Br
H
C
CH3
Br H
CH3
C
C
Br H
H
Br
H
Br
C
CH3
C
H
H
C
H
Br
H
Ch. 8 - 88

Anti-Markovnikov addition of hydrogen
bromide to alkynes occurs when
peroxides are present in the reaction
mixture
H
Br
peroxides
Br
H
(E) and (Z)
(74%)
Ch. 8 - 89
20. Oxidative Cleavage of Alkynes
R
C
C
R'
OR
R

Ph
C
C
1. O3
R'
2. HOAc
1. KMnO4, OH
+
2. H3O
RCO2H
+ R'CO2H
RCO2H + R'CO2H
Example
C
C
CH3
1. O3
2. AcOH
PhCO2H + CH3CO2H
Ch. 8 - 90
21. How to Plan a Synthesis:
Some Approaches & Examples

In planning a synthesis we often have
to consider four interrelated aspects:
1. Construction of the carbon
skeleton
2. Functional group interconversions
3. Control of regiochemistry
4. Control of stereochemistry
Ch. 8 - 91
21A. Retrosynthetic Analysis

How to synthesize
?
OH
● Retrosynthetic analysis
OH
(target molecule)
(precursor)
Ch. 8 - 92
● Synthesis
Markovnikov addition
of H2O
H+
H2O
or
OH
1. Hg(OAc)2, THF-H2O
2. NaBH4, OH
Ch. 8 - 93

How to synthesize
OH
?
● Retrosynthetic analysis
OH
(target molecule)
(precursor)
● Synthesis
1. BH3-THF
2. H2O2, OH
anti-Markovnikov addition of H2O
OH
Ch. 8 - 94
21B. Disconnections, Synthons, and
Synthetic Equivalents

One approach to retrosynthetic
analysis is to consider a retrosynthetic
step as a “disconnection” of one of the
bonds

In general, we call the fragments of a
hypothetical retrosynthetic
disconnection Synthons
Ch. 8 - 95

Example
How?
Ph
H
Br
Br
CH3
Ph
● Retrosynthetic analysis
(i)
Br
Ph
Br
CH3
Ph
CH3
(gem-dibromide came from addition
of HBr across a C≡C bond)
Ch. 8 - 96
● Retrosynthetic analysis
synthons
(ii)
Ph
CH3
Ph
+
CH3
disconnection
H3C
I + Ph
Na
synthetic equivalent
Ch. 8 - 97
● Synthesis
Ph
H
NaNH2
liq. NH3
-30oC
Ph
Na
H3C
I
(via an SN2
reaction)
Br
Ph
Br
CH3
HBr
(excess)
Ph
CH3
Ch. 8 - 98
21C. Stereochemical Considerations
How?
H3C
Br
Br
CH3
H3C
CH3
Ch. 8 - 99

Retrosynthetic analysis
● The precursor of a vicinal dibromide
is usually an alkene
● Bromination of alkenes are anti
addition
Br
Br
H3C
Br
H3C
CH3
o
(rotate 180 )
(anti addition of H2)
H3C
CH3
H3C
CH3
Br
(anti addition
of Br2)
CH3
Ch. 8 - 100
● Synthesis
H3C
1. Li, liq. NH3
CH3
H3C
2. NH4Cl
CH3
(anti addition of H2)
Br2/CCl4
Br
H3C
Br
CH3
Br
same
as
(anti
addition
of Br2)
CH3
H3C
Br
Ch. 8 - 101
 END OF CHAPTER 8 
Ch. 8 - 102