Stereoselective reactions of alkenes - Massey University, The

25 Pages·2006·1.26 MB·English

1
Stereoselective reactions of alkenes
I
I
2
O
Me O H Me O
O
• Earlier, we saw that stereospecific reactions can produce single diastereoisomers
• If there is a pre-existing stereogenic centre reactions can be stereoselective
• In other words, the faces of the alkene are diastereotopic
• Following two examples show highly diastereoselective iodolactonisations
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
• If the reactions are under kinetic control we have to look at other factors and need to
. look at conformation again...
..
Advanced organic
2
Stereoselective reactions of alkenes II
O O
Me Me Me
m-CPBA
+
Me SiMe Ph Me SiMe Ph Me SiMe Ph
2 2 2
>95% <5%
• Two diastereoisomers formed as a result of attack from the two diastereotopic faces
• Look at possible conformations...
• Arguably the lowest energy conformations have greatest separation of substituents
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
• The control of conformation by the interaction of methyl group and stereocentre is
. called allylic strain or A(1,3) strain
..
Advanced organic
3
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
Advanced organic
4
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
Advanced organic
5
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
Advanced organic
6
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
Advanced organic
7
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
..
Advanced organic
8
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
Advanced organic
9
Directed reactions
SiMe t-BuO H SiMe
3 2 3
Me Me
VO(acac) TBAF
Me Me 2 Me Me
O
O OH
H OH OH
25:1
• It is possible to form the desired allylic epoxide in a highly selective manner by
utilising a temporary blocking group
• The silyl group causes one conformation to predominate & can be removed at end
• As silyl group bigger than methyl reaction more selective
• Other diastereoselective reactions of alkenes can be controlled by a directing group
• Below is an example of cyclopropanation by the Simmons-Smith reagent
CH I
2 2
Zn Zn I
OH OH
O CH
2 H
H C Zn
2 H
C I + I O
I Zn
H
carbenoid >98% de
Advanced organic
10
Stereoselective reactions of enolates
M
O O
O
E
R2 R2 R2
R1 R1 R1
H H H E
H
• The stereoselectivity of reactions of enolates is dependent on:
• Presence of stereogenic centres on R1, R2 or E (obviously!)
• Frequently on the geometry of the enolate (but not always)
C-α re face C-α si face
M M
O O
MO R2 MO H
α R2 α α H α
R1 R1
R1 H R1 R2
H R2
(Z)-enolate (E)-enolate
(cis) (trans)
C-α si face C-α re face
• Use terms cis and trans with relation to O–M to avoid confusion
Advanced organic