1 1 Chapter 8 Alkenes: Reactions and Synthesis (not Simmons-Smith reactions or epoxidation, not 8.10 and not 8.11) Synthesis via elimination reactions Halogenation and halohydrin formation Addition of water to alkenes(oxymercuration, hydroboration-oxidation) Carbene reactions (:CCl 2 ) Hydrogenation (H 2 /cat.) Dihydroxylation (OsO 4 ), diol cleavage with IO 4 - Ozonolysis Stereochemistry of alkene addition Topics 2 Synthesis of alkenes via elimination reactions: Base elimination + Br- + H 2 0 Acid-catalyzed elimination OH CH 3 H 2 SO 4 , H 2 O THF + H 2 0 THF = a solvent that is miscible with water O KOH, ethanol Br H OH
Transcript
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Chapter 8 Alkenes: Reactions and Synthesis(not Simmons-Smith reactions or epoxidation, not 8.10 and not 8.11)
Synthesis via elimination reactions
Halogenation and halohydrinformation
Addition of water to alkenes(oxymercuration, hydroboration-oxidation)
Carbene reactions (:CCl2)
Hydrogenation (H2/cat.)
Dihydroxylation (OsO4), diolcleavage with IO4
-
Ozonolysis
Stereochemistry of alkeneaddition
Topics
2
Synthesis of alkenes via elimination reactions:
Base elimination
+ Br- + H20
Acid-catalyzed elimination
OHCH3
H2SO4, H2O
THF
+ H20
THF = a solvent that is miscible with waterO
KOH, ethanol
Br
H OH
2
Quick review: Addition of HX (X=Cl, Br, I) to alkenes
achiral
The reaction goes through the more stable carbocation.3
This reaction is regiospecific
CH3 CH3
Br
Markovnikov
CH3
Br
CH3
Br
CH3
Br
CH3
Br
Non-Markovnikov
HBr
ether
CH3
CH3
Br
CH2CH3
CH2CH3
H
CH3
Br
CH2CH3H
CH3
Br
CH2CH3H
CH3
Br
CH2CH3H
HBr
CH3
H
CH2CH3Br
CH3
H
CH2CH3Br
CH3
H
CH2CH3Br
CH3
H
CH2CH3Br
All of the possible stereoisomers are formed
When both carbocations have similar stability:
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3
H
CH3
CH3
Br
cis
Addition from the top or bottom
H
CH3
CH3
Br H
CH3
Br
CH3
trans
carbocationintermediate
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6
Halogenation: Addition of X2
C C
H
HH
H Cl2ClCH2CH2Cl
Br2
Br
Br
What is a possible mechanism?
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7
From H-X addition:
By this mechanism, should see 50:50 mixture of cis and trans.
In reality, only the trans isomer is observed.
Reaction occurs with anti stereochemistry (atoms add from opposite faces of the double bond.
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Halogenation: Addition of X2
Bromonium ion “shields” one face of ring. Only the opposite face is available.ANTI addition
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Halohydrin formation
OH
BrBr2 / H2O
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Br
Br--Br
+ Br- + OH2
Who wins?
[H2O] >> [Br-]
Halohydrin formation
OH
BrBr2 / H2O
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Br
Br--Br
+ Br- + OH2
Br
OH2
[H2O] >> [Br-]
+ H3O+
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Halohydrin formation
Bond from bromonium to the more substituted carbon is weaker.
More + charge on more substituted carbon
Br2/H2OCl2/H2O I2/H2O
Br Br
H3C
Br
HHO
H3C
H
Br +
H3C
OH2
Br
H
H3C
HO
Br+
HH3C
OH2
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with deprotonationstep (next slide)
Br +
H
Br
H
H3C
HOH3C
OH2
Br
H
H3C
OH
H+
OH2
Paying attention to details when you write out the mechanism
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Halohydrin formation (2)
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CH3 CH3
H
OH
Br
CH3
H
OH
Br
+
anti addition
Regiospecific: the –OH (from H2O as the nucleophile) becomes attached to
the site of the more stable carbocation. CH3
H
Br
OHNone of the other isomers are formed.
Bromohydrin formation with NBS
NBS reacts slowly with water to produce a low constant level of Br2.This is a safer way of running this reaction. Note ring doesn’t react.
N
O
O
Br N
O
O
HH2O/DMSO
+ Br2
O
SCH3 CH3
DMSOhelps to dissolve
the reactants14
Br2 source
nucleophile
solvent
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Which product will result from the following reaction?
1. 2.
3.
4. 5.
Cl2
CH2Cl2
Which of the compounds will result from the reaction of NBS/H2O/DMSO with 1-methylcyclopentene?
1. 2.
3.
4. 5.
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Hydration of alkenes
goes throughHX additionmechanism
H3PO4, pH 0
250 °C+ H2O
OH
Ethanol
Fumarase, pH 7
37 °C
OH
+ H2O
HOOC
COOH
COOHHOOC
*
In industry
In living cells
not useful on small scale in the laboratory
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Electrophilic Addition Reactions Review
C CH-Br
C
H
C
Br
C C
H
+ Br -
Addition of H-X
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Electrophilic Addition Reactions
C CBr-Br
C
Br
C
Br
C C
Br+ Br -
Addition of X-X
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Electrophilic Addition Reactions
C CBr-Br
C
Br
C
OH
H2O
C C
Br+ H2O C
Br
C
O
HH O
HH
+ H3O+
Halohydrin Formation
+
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Electrophilic Addition Reactions
C C C
H
C
OH
H2O
H2SO4
+ H2O C
H
C
O
HH O
HH
O
HH
H
C C
H
Acid-Catalyzed Hydration
+ H3O+
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Hydration reactions in the Lab
Two-step processes
_______________
_______________
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CH3 CH3
OH
CH3 CH3
H
H
OH
CH3
H
H
OH
"Non-Markovnikov" and Syn addition
Markovnikov
1. Hg(OAc)2, H2O2. NaBH4
1. BH32. H2O2 /OH-
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Hg
O
O
O
OHg
O
O
O
O
Oxymercuration
Attack on more substituted carbon(it has more positive charge character)
HgO
O
+O
H
H
Hg O
O
OH
Hg O
O
O
H
H
+
NaBH4O
H
+ Hg + 2 HOAc
+
Markovnikov, but not stereospecific23
The reaction stops here but this product
is not isolated
O
H
H
Hydroboration
Borane is a good electrophile with an empty p-orbital
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Hydroboration: syn addition
B becomes attached to the less substituted carbon
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H BH2H OH
HH H H
NaOH, H2O2
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The C-B bond is replaced with a C-O bond.
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What is the product of reaction of 1-methylcyclohexene with Hg(OAc)2/H2O/THF followed by NaBD4? (D = 2H)
1. 2.
3.
4. 5.
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Hydrogenation:
Addition of H2 gas to alkenes gives alkanes (or cycloalkanes).
Both H atoms add to the same face of alkene, SYN addition.Catalyst: often Pd/C or PtO2 (Adams’ catalyst)
H2
catalyst
H
H
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Hydrogenation:
The double bond is hydrogenated or reduced by the addition of H2.
Other multiple bonds are usually unaffected by these conditions.
Which compound is the best starting material for hydrogenation to decalin shown below?
1. 2.
3.
4. 5.
H
HH2 (< 1atm)
Pd/C
?
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______________
O H O HO sO 4
N aH SO 3/H 2O
CH3
OH
HOH
CH3
OH
HOH
Syn
Anti addition products are not formed
CH3
OH
HOH
CH3
OH
HOH
CH3
H
OsO4
NaHSO3/H 2O
Markovnikov’s rule not needed
1)
2)
1)
2)
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Mechanism: Why Syn?
OsO O
O O
OsO O
O O
HO OH
OsHO OH
O O
NaHSO3/H2O
: :
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Diol cleavage with IO4-
H CH3
HO OH+ HIO4 H CH3
O O
I
O OHO
H CH3
O O
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Alkene Cleavage
C=C bonds can be completely broken.
Two methods:Diol formation, followed by cleavage with HIO4
