More substrate control, including allylic strain and directed reactions.

1. LECTURE TWO
substrate control
gareth j rowlands
©fensterbme@flickr

2. 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%
epoxidation

3. no
in
change
©e-magic@flickr stereocentre

4. 1,3)
allylic (A
Me
H
strain
Me Me
H H Me H H Me
Me H Me Me
Me H
disfavoured

5. 1,3)
allylic (A
Me
H
strain
Me Me
H H Me H H Me
Me H Me Me
Me H
disfavoured

6. 1,3)
allylic (A
Me
H
strain
Me
H H Me H H Me
H H H Me
Me H
little difference

7. 1,3)
allylic (A
Me
H
strain
Me
H H Me H H Me
H H H Me
Me H
little difference

8. 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

9. 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

10. 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 "

11. 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

12. 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

13. 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%

14. 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

15. 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

16. 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

17. 1,3)
allylic (A
strain
H2B H
Me H H BH2 O
Me H
OBn Me
H
BnO
H
O Me
favoured

18. H
OH
O
H OH
O
Et
H
O
H
O OH
O
H
O
O
HO
monensi,n60&262
, 101 2979
J. Am. Chem. Soc, 1 ©AJC1@flickr

19. acyclic O
Et
substrate
O H
HO 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

20. directed
reactions

21. normal OAc
epoxidation
O
OAc
mCPBA 63%
OAc
O
37%

22. reason...
OAc
H
"O "

23. directed OH
epoxidation
O
OH
mCPBA 8%
OH
O
92%

24. reason...
Ar
O
O
O H
H
O
H

25. acyclic
directed epoxidation
O
Me Me
Me H OH
Me Me m-CPBA 95
O
Me H OH Me Me
Me H OH
5

26. 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

27. 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

28. 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

29. acyclic
directed Me
epoxidation Me
O
Me t-BuO2H OH
VO(acac)2 19
Me
Me
H OH Me
O
OH
1

30. how
why
no C3 substituent

31. R 50° HO
R R R R
R HO H R H R
50°
1,2)
(A strain

32. 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

33. myc,i1n323
oleaen.do1996, 118 1
h m Soc,
J. Am. C
O
O
OH O
O O NMe2
H
OH
O O
H
O
O
OH ©Microbiology 148, 405 (2002)

34. 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

35. 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

36. OH O
H
HO O
H Et
CO2H Et O OH
Et
alocid8,A0, 2933
las c, 197 10
J. Am. Chem. So

37. 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

38. cyclic
transition state
Et
R
H
Ar H
L
O
V t-Bu
O O
L

39. other directed
reactions
O O
Ir PF6
Py PCy3
N N
H2
dr = 99:1
H H