Reactions of alkenes: stereospecific reactions

32 Pages·2007·3.14 MB·English

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Reactions of alkenes: stereospecific reactions
• Diastereospecific - reaction permits only one diastereoisomer to be formed
control relative stereochemistry not absolute stereochemistry
• Electrophilic epoxidation via a concerted process is a good example...
H Ph O
m-CPBA
Ar
H Ph
O Ph H Ph H
Note: only
O H (E) anti controlling relative
stereocheimstry
O
H H O NOT absolute
m-CPBA stereochemistry
H Ph
H H
Ph H
Ph Ph Ph Ph
(Z) syn
Iodolactonisation
• Proceeds via an iodonium species followed by intramolecular ring-opening
• Geometry of alkene controls relative stereochemistry
I I
I
I
2
O
O
H
Me O H Me O Me O
Me O H O O
I
(E) anti
Me I
I
2
O
O H Me O O
(Z) syn
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Stereoselective reactions
• If there is a pre-existing stereogenic centre then reaction can be stereoselective
• In such reactions two diastereoisomers could be formed but one is favoured
Me Me Me Me
I I
2 I 2
OH I
O O OH O O
O O
88% de
82% de
• These cyclisations are probably under thermodynamic control
• This means the reactions are reversible and equilibrate
• Therefore the product is the most stable compound (anti)
• Epoxidation is irreversible and the reaction is under kinetic control
• So how do we explain the following observations...
O O
Me Me Me
m-CPBA
+
Me SiMe Ph Me SiMe Ph Me SiMe Ph
2 2 2
>95% <5%
O O
Me Me
m-CPBA Me Me Me Me
+
SiMe Ph
2 SiMe Ph SiMe Ph
2 2
61% 39%
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Conformations in allylic systems
HH HH MMee HH HH MMee
HH HH
Me HH MMee
if no cis substituent
rotate then only small
H bond MMee HH energy difference
Me
lowest energy: H slightly higher energy: Me
eclipses plane of alkene eclipses plane of alkene
HH HH MMee HH HH MMee
X
MMee HH MMee MMee
Me
cis substituent
MMee HH present then only
H
ONE conformation
Me Me high energy: Me–Me
lowest energy: H
interaction disfavours
eclipses plane of alkene
conformation
• Arguably the lowest energy conformations have greatest separation of substituents
• The control of conformation in allyl systems is called allylic strain or A(1,3) strain
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Stereoselective reactions of alkenes III
• Apply this knowledge to the real system...
X
O
O
Me m-CPBA Me Me
Me H SiMe2Ph Me H SiMe2Ph Me H SiMe2Ph
<5%
>95%
m-CPBA
m-CPBA
silyl group blocks
X
approach
Me Ph Me Ph H H H
lowest energy H H Si Me H H Si Me Me Me
conformation
Me H Me H
O Si Me
Me Me Ph Me
formation of minor
m-CPBA diastereoisomer results
from m-CPBA
approaching alkene in
above conformation or
m-CPBA approaches approaching passed
from unhindered face the silyl group
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Importance of A(1,3) strain
O O
Me Me
m-CPBA Me Me Me Me
+
H SiMe Ph
2 H SiMe Ph H SiMe Ph
2 2
61% 39%
• The importance of a cis-substituent is made clear by the reduced stereoselectivity
• This is explained as follows...
m-CPBA
X
PPhh MMee Ph Me
O
lowest energy MMee HH SSii MMee Me H Si Me Me Me
conformation
HH H
gives major product HH H
O H SiMe Ph
2
MMee Me 61%
Me Me
m-CPBA attacks both conformations low
form least hindered energy -- so mixture of
H SiMe Ph face products
2
O
MMee HH HH Me H H
O
HH MMee H Me Me
Me
X
SSii MMee
Si Me H SiMe Ph
2
PPhh MMee Ph Me 39%
m-CPBA
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Other reactions...
• Epoxidation is not the only stereoselective reaction of alkenes
• Below is an example of hydroboration, a useful reaction that you should be familiar
with...
H Me Me H Me H Me H O H Me H Me
2 2
BH NaOH
3
O OBn O H B OBn O OH OBn
2
74% de
Attack from the least sterically
demanding face of the alkene
O O
as it resides in the most
H CH OBn H CH OBn
2 2
favoured conformation.
Me Me
H H
Followed by stereospecific
H B H
2
Me Me oxidation
H B H
2
preferred
approach Selectivity in addition to cis alkenes
H S L
S L H
S H R 1 1
R R R
3 3
L H S
L R1
R1 R1 R1
S = smaller group favoured destabilised by repulsion between C-1 & C-3
L = larger group substituents or A(1,3) strain
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Directed epoxidation
OH OH OH
reagent
+
O O
reagent: syn t anti
m-CPBA 92 : 8
t-BuO H, VO(acac) 98 : 2
2 2
• A hydroxyl group can reverse normal selectivity and direct epoxidation
• Epoxidation with a peracid, such as m-CPBA, is directed by hydrogen bonding and
favours attack from the same face as hydroxyl group
• The reaction with a vanadyl reagent results in higher stereoselectivity as it bonds /
chelates to the oxygen
hydrogen
Ar
bond O O
t-BuO
Me O O Me
O V V
O O O O O
O H
H
Me Me
O
vanadyl acetylacetonate H
H
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Directed epoxidation in acyclic systems
O O
Me Me
m-CPBA Me Me Me Me
+
Me H OH Me H OH Me H OH
95 5
hydrogen
Ar bond
Me H H
O O Me Me
O Me H OH
O H H
H O O
Me H
Me H O O H
O
Me
Me H
Ar
Me
favoured disfavoured
conformation conformation
• Hydroxyl group can direct epoxidation in acyclic compounds as well
• Once again, major product formed from the most stable conformation
• Thus the cis methyl group is very important
• The minor product is formed either via non-directed attack or via the less favoured
. conformation
..
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Directed epoxidation: effect of C-2 substituent
Me t-BuO H Me Me
2
VO(acac)
Me 2 Me + Me
O O
H OH OH OH
19 : 1
steric
interaction
Me t-Bu
O
L
V
H
O H O L
favoured disfavoured
conformation as H Me H Me conformation as
only Me & H eclipse Me & Me eclipse
O L O Me
H
V
L
O
t-Bu H
• The presence of a substituent in the C-2 position (Me) facilitates a highly
diastereoselective reaction
• The preferred conformation minimises the interaction between the two Me (& Me)
groups
• With C-2 substituent (H) there is little energy difference between conformations
• Therefore, get low selectivity
Me
t-BuO H
2 H
Me Me VO(acac) Me Me Me Me O H
2 H too small to
+
O O H H differentiate
H OH OH OH conformations
O L
2.5 : 1
V
L
O
t-Bu
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Substrate control in total synthesis
Ph Ph
VO(acac)
O O O O OH OH OTIPS 2 O O O O OH OH OTIPS
t-BuOOH
O N C C Me 91% O N C C Me
1 13 1 13
100% d.e.
Me Me Me Me Me Me Me Me O Me Me
Bn Bn
• Directed epoxidation from the synthesis of oleandomycin aglcon
• Glycosylated version (R=sugar) is a potent antibiotic from streptomyces antibioticus
• David A. Evans and Annette S. Kim, J. Am. Chem. Soc. 1996, 118, 11323
t-Bu
O
L
V
O L O
O
H R1 Me
O H
H
Me Me
OH
R2
C
versus 13 Me
Me O OR
H
C
1
O OR
H
O R2
Me
H R1
Oleandomycin aglycon
O L (R=H but should be a sugar)
V
steric
L
O interaction
t-Bu
123.702 Organic Chemistry