LECTURE TWO

strate control
sub

gareth j rowlands
©fensterbme@flickr
acyclic
substrate control
O O
Me m-CPBA Me Me

Me SiMe2Ph Me SiMe2Ph Me SiMe2Ph

>95% <5%

Me Me O O
m-CPBA Me Me Me Me

SiMe2Ph SiMe2Ph SiMe2Ph

61% 39%

idation
epox
 no
in
change
ce ntre
©e-magic@flickr stereo
 1,3)
allylic (A
Me
H
strain
Me Me

H H Me H H Me
Me H Me Me
Me H

disfavoured
 1,3)
allylic (A
Me
H
strain
Me Me

H H Me H H Me
Me H Me Me
Me H

disfavoured
 1,3)
allylic (A
Me
H
strain
Me

H H Me H H Me
H H H Me
Me H

little difference
 1,3)
allylic (A
Me
H
strain
Me

H H Me H H Me
H H H Me
Me H

little difference
acyclic Me m-CPBA
O
Me

substrate control Me SiMe2Ph Me SiMe2Ph

>95%

"O "

Me Ph Me Ph
O

X
H H Si Me H H Si Me
Me H Me H
Me Me
acyclic Me m-CPBA
O
Me

substrate control Me SiMe2Ph Me SiMe2Ph

>95%

"O "

Me Ph Me Ph
O

X
H H Si Me H H Si Me
Me H Me H
Me Me
acyclic Me m-CPBA
O
Me

substrate control Me SiMe2Ph Me SiMe2Ph

>95%

Me Ph Me Ph
H H Si Me H H Si Me
Me H Me OH
Me Me
"O "
acyclic Me Me m-CPBA Me
O
Me Me
O
Me

substrate
SiMe2Ph SiMe2Ph SiMe2Ph
61% 39%

control Ph Me Ph Me
Me H Si Me Me H Si Me
H H H
OH
Me Me

Me Me m-CPBA attacks
least hindered
face
H SiMe2Ph

O
Me H H Me H H
H Me H Me
Si Me Si Me
Ph Me Ph Me
acyclic substrate control
S H R

preferred L R1
approach

S H L S H L

R
1 R
1 R
L H 3 S 3

R1 R1 R1
destabilised by repulsion
favoured between C-1 & C-3 substituents
known as A(1,3) strain
other
examples of substrate
control Me
Bu OEt

i. LDA Me O
Bu OEt ii. MeI 83%

Me O Me
Bu OEt

Me O
27%
 1,3)
allylic (A
i. LDA Me
Bu OEt ii. MeI Bu OEt
Me O

strain
Me O

I
Me
Me H Me
OEt Me OEt
H O O
H
Li H
Bu Bu
favoured
conformation
 1,3)
allylic (A
strain
S H O LDA S H OEt S H OLi

L OEt L OLi L OEt

≡
preferred preferred
approach approach

O S H S H
S H
E OEt OLi
L OEt L L
E H
OLi OEt
other
examples of substrate
control
H Me Me H Me H Me H2O2 H Me H Me
BH3 NaOH

O OBn O H2B OBn O OH OBn

74% de

O O
H CH2OBn H CH2OBn
H Me H Me
H2B H
Me Me
1,3)
allylic (A
H2B H

strain
 1,3)
allylic (A
strain
H2B H
Me H H BH2 O
Me H
OBn Me
H
BnO
H
O Me

favoured
 H
OH
O
H OH
O
Et
H
O
H
O OH
O
H
O

HO

monensi,n260&262
., 101
S o c , 1979
J. Am. C h em ©AJC1@flickr
acyclic Et

H O

substrate
HO O H O
H
O
H
H

control
O
O O HO

OH OH

i. BH3
H Me Me ii. H2O2 H Me H Me
NaOH

74% de
O OBn O OH OBn

OH i. BH3 OH
H Me H Me ii. H2O2 H Me H Me
NaOH
Me
85% de Me
H
O OMe OH O OMe
directed
reactions
normal OAc
epoxidation
O
OAc
mCPBA 63%
OAc

37%
reason...

OAc

"O "
directed OH
epoxidation
O
OH
mCPBA 8%
OH

92%
reason...
Ar

O
O
O H
H
O

H
 acyclic
directed epoxidation

O
Me Me

Me H OH
Me Me 95
m-CPBA
O
Me H OH Me Me

Me H OH
5
 acyclic Me Me m-CPBA Me
O
Me

directed Me H OH Me H OH

epoxidation
Ar

O O
O Me H OH
O H
H
Me H
Me H O
Me H Me

Me
1,3)
allylic (A strain
 acyclic Me Me m-CPBA Me
O
Me

directed Me H OH Me H OH

epoxidation

120° OH
Me H
Me H Me

1,3)
favoured allylic (A strain
 acyclic Me Me m-CPBA Me
O
Me

directed Me H OH Me H OH

epoxidation
Me H H
Me Me
H O O
O H
O

Ar

disfavoured allylic (A 1,3)

strain
 acyclic
directed Me
epoxidation Me
O
Me t-BuO2H OH
VO(acac)2 19
Me
Me
H OH Me
O
OH
1
how
why

substituent
no C3
 R 50° HO
R R R R
R HO H R H R
50°

1,2)
(A strain
 Me t-Bu O
L
H V
O H O L
H Me H Me
O L O Me
V H
O L
t-Bu H

favoured
1,2)
(A strain
 m y c in
oleahenm.dSoo
c, 19 9 6, 11 8, 1 1323
J. Am. C

O
O

OH O

O O NMe2
H
OH
O O
H
O

O
OH ©Microbiology 148, 405 (2002)
 O
O
Ph
O
OH
NMe 2
O O O O OH OH OTIPS O
O
H
OH
O
O H
O
O N Me
O
Me Me Me Me Me OH

Bn
VO(acac)2
t-BuOOH
91%
100% de
Ph

O O O O OH OH OTIPS

O N Me
Me Me Me O Me Me
Bn
 H t-Bu O
L
H V
O R2 O L
H R1 versus H R1
O L O H
V H
O L
t-Bu R2

favoured
1,2)
(A strain
 OH O
H
HO O
H Et
CO2H Et O OH
Et

alocid A
las c, 1978, 100, 2933
J. Am. Chem. So
long range directed OH O
H

epoxidation HO
CO2H Et
H
O
Et
O OH
Et
Et

Et
OH

MeO
t-BuO2H
VO(acac)2
dr = 8:1

Et
H
O AcOH
Et Ar O
OH Et
75%
OH
Et
MeO
 cyclic
tran sition state
Et
R
H
Ar H
L
O
V t-Bu
O O
L
other directed
reactions

O O
Ir PF6
Py PCy3
N N
H2
dr = 99:1
H H