Chapter 8
(except 8.10, 8.11)
CHM 136H
Synthesis and Reactions of Alkenes
1
Chapter 8: Alkene Reactions
- alkene synthesis
- stereochemistry and regiochemistry of addition reactions
- addition of HBr, Br2, Br2/H2O
- addition of H2O: 1. oxymercuration
2. hydroboration
- hydrogenation: H2
- formation of 3-membered rings: 1. dichlorocarbene
2. Simmons-Smith
3. Epoxidation
- formation of 1,2-diols: OsO4
- cleavage of alkenes: O3/Zn, HIO4
1
2
Synthesis of alkenes: elimination reactions
addition
elimination
+ A-B
Elimination with base:
Acid-catalyzed elimination:
KOH
H2SO4
+ Br– + H2O
+ H2O
CH3CH2OH
H2O,
3
syn addition:
A and B add to
same face of alkene
anti addition:
A and B add to
opposite faces of alkene
Reactions of alkenes: addition reactions
- selectivity in addition:
1. regioselectivity of addition: Markovnikov's rule
2. stereochemisty of addition: not selective, carbocation intermediate
A-B = H-X
A-B A-B
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3
4
Halogenation:
What mechanism leads to this anti addition?
+ Br2
CCl4
5
- selectivity in addition: A-B = X2
The mechanism:
reaction at either face
of alkene equally likely
Br- attacks backside of the
more substituted carbon
anti addition
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5
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(Z)-2-butene
Addition of Br2 to (Z)-2-butene
Stereochemistry of alkene addition reactions
(E)-2-butene
Addition of Br2 to (E)-2-butene
Stereochemistry of alkene addition reactions
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8
bromonium ion
Mechanism very similar to
halogenation except
nucleophile in second step is H2O
++
Same reaction of cyclohexene and X2 IN H2O:
a bromohydrin
deprotonation
Who wins?
Br2/H2OCl2/H2O
9
Overall reaction for the formation of a bromohydrin:
- water as solvent and reactant!
H2O
Br2 +
racemic mixture
+
"addition of HOBr"
DMSO
- anti addition
- regioselective: the –OH (from H2O nucleophile)
bonds to the more substituted carbon
10Syn products not formed
less substituted
more substituted
9
10
NBS reacts slowly with water to produce a low constant [Br2]:
Bromohydrin formation with NBS
H2O
+ Br2
11
Typical solvents: alkanes, ether, THF, CH2Cl2
not HOH or ROH
anti addition
Brief summary:
X2
X2 = Cl2, Br2
+
12Typical solvent: mixtures of THF/H2O or DMSO/H2O
X2
X2 = Cl2, Br2
+
anti addition
11
12
Chapter 8: Alkene Reactions
- alkene synthesis and stereochemistry and
regiochemistry of addition reactions
- addition of HBr, Br2, Br2/H2O
- addition of H2O: 1. oxymercuration
2. hydroboration
- hydrogenation: H2
- formation of 3-membered rings: 1. dichlorocarbene
2. Simmons-Smith
3. Epoxidation
- formation of 1,2-diols: OsO4
- cleavage of alkenes: O3/Zn, HIO4,
14
- addition of water to form an alcohol Hydration of alkenes
In living cells:
fumarase
+ H2O
+ H2O
cat. H2SO4
D (heat)
In (big!) flasks: catalytic amount
not useful on the laboratory scale
H2O + H2SO4 + HSO4
-
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14
The acid is a catalyst, being
regenerated at the end of the reaction.
Markovnikov product
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Mechanism:
+
two-step process
1. Oxymercuration:
2. Hydroboration
Hydration reactions in the lab
two-step process
1. Hg(OAc)2, H2O/THF
2. NaBH4
Markovnikov product
+
1. BH3, THF
2. H2O2, OH
–
non-Markovnikov product
syn addition
••
d+ d–d–
regioselective reaction:
regioselective reaction:
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15
16
stable compound; can be isolated
d+ d–
d–
Mechanism of oxymercuration:
deprotonation
1. Hg(OAc)2, H2O/THF
- 3 elementary steps
- approach from other face
of alkene equally likely
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H2O
− H3O
+
H2O
+ enantiomer
+ enantiomer
+ enantiomer
Overall Markovnikov addition of water to C=C:
1. Hg(OAc)2, H2O
2. NaBH4
2. NaBH4Demercuration:
+ enantiomer
18
+ enantiomer + enantiomer
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2. Hydration by hydroboration
borane
+
H2O2, NaOH
THF
good electrophile
19
BH2 and H add to the same face
of the alkene = syn addition….
‡
d+
d−
….at the same time.
organoborane
H2O2, NaOH
Mechanism of hydroboration:
20
19
20
Why non-Markovnikov regioselectivity?
Transition state for non-Markovnikov addition is more favourable
d+
d–
‡
and stericallyboth electronically
Reaction proceeds by lower energy (more stable) transition state:
more steric crowdingless steric crowding
partial 3o carbocation partial 2o carbocation
→ B bonds to the less substituted carbon
21
‡
d+
d–
Reaction stereochemistry:
‡
d+
d–
H2O2, NaOH H2O2, NaOH
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‡
d+
d–
21
22
Overall reaction:
1. BH3, THF
2. H2O2, NaOH
racemic mixture
non-Markovnikov and syn addition of H-OH to C=C
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Chapter 8: Alkene Reactions
- alkene synthesis and stereochemistry and
regiochemistry of addition reactions
- addition of HBr, Br2, Br2/H2O
- addition of H2O: 1. oxymercuration
2. hydroboration
- hydrogenation: H2
- formation of 3-membered rings: 1. dichlorocarbene
2. Simmons-Smith
3. Epoxidation
- formation of 1,2-diols: OsO4
- cleavage of alkenes: O3/Zn, HIO4
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24
Hydrogenation
Addition of H2 gas to alkene C=C forms an alkane
H2
catalyst
25
H atoms add to the same face of the alkene from catalyst surface
Catalytic hydrogenation
Examples: Pt/carbon, Pd/carbon, PtO2
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26
Polar multiple bonds and aromatic rings are usually unaffected
Chapter 8: Alkene Reactions
- alkene synthesis and stereochemistry and
regiochemistry of addition reactions
- addition of HBr, Br2, Br2/H2O
- addition of H2O: 1. oxymercuration
2. hydroboration
- hydrogenation: H2
- formation of 3-membered rings: 1. dichlorocarbene
2. Simmons-Smith
3. Epoxidation
- formation of 1,2-diols: OsO4
- cleavage of alkenes: O3/Zn, HIO4
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28
Addition of carbenes to alkenes
Common features
• sp2 hybridized carbon
• one unhybridized p orbital
• 6 electrons around the C centre
29
CarbocationCarbene
two bonds around C atom three bonds around C atom
one lone pair of electrons
around C atom
no nonbonding electrons
around C atom
Charge: 0 Charge: +1
Differences
••–
– H2O – Cl
1. Dichlorocarbene:
••
–
–
+ HCCl3
KOH
E.g.
30
syn
addition
29
30
31
Practice: write down the mechanism and the final product of the
following reaction.
CH2I2
2. Simmons-Smith reaction:
+ Zn(Cu)
+ CH2I2
Zn(Cu)
ICH2ZnI in the presence of alkenes, can behave as “:CH2” + ZnI2
ICH2ZnI
syn addition
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31
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3. Epoxidation: a 3-membered ring with an O instead of a C atom
MCPBA
MCPBA
CH2Cl2
epoxide
33
cat. H3O
+
H2O
+
34
Epoxides react with aqueous acid to give trans diols
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Chapter 8: Alkene Reactions
- alkene synthesis and stereochemistry and
regiochemistry of addition reactions
- addition of HBr, Br2, Br2/H2O
- addition of H2O: 1. oxymercuration
2. hydroboration
- hydrogenation: H2
- formation of 3-membered rings: 1. dichlorocarbene
2. Simmons-Smith
3. Epoxidation
- formation of 1,2-diols: OsO4
- cleavage of alkenes: O3/Zn, HIO4
Dihydroxylation using a catalytic amount of OsO4
cat. OsO4
NMO
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Acetone/H2O
+
NMO:
(N-methylmorpholine N-oxide)
m.p. 180-184 °C
acetone/H2O mixed solvent
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36
NMO
NMO
37
H2O
H2O
Mechanism
Chapter 8: Alkene Reactions
- alkene synthesis and stereochemistry and
regiochemistry of addition reactions
- addition of HBr, Br2, Br2/H2O
- addition of H2O: 1. oxymercuration
2. hydroboration
- formation of 1,2-diols: OsO4
- hydrogenation: H2
- formation of 3-membered rings: 1. dichlorocarbene
2. Simmons-Smith
3. epoxidation
- cleavage of alkenes: O3/Zn, HIO4
37
38
1. Dihydroxylation and cleavage of 1,2-diol
cis-1,2-diol
HIO4 H2O/THF
39
cat. OsO4
NMO
Alkene cleavage reactions
2. Ozonolysis Reagents: 1. 2. Zn/CH3COOH
O3
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40
?Practice: which of the following alkenes will yield
the products shown upon epoxidation?
H2
Pd/C
Br2
CH2Cl2
MCPBA
H2O
THF
1. BH3,THF
2. H2O2, NaOH
1. Hg(OAc)2, H2O/THF
2. NaBH4
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Summary
cat. OsO4
NMO
HBr
ether
NaOH
H2O,
cat. H2SO4
D (heat)
:CR’2
1. O3
2. Zn/H+
HIO4
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