Use of stoichiometric amounts of a chiral source. The usual suspects will be discussed, including borane reagents (mostly pinene derivatives) and the Brown allylation.

1. LECTURE FOUR
chiral reagents
gareth j rowlands

2. O
(R)-muscon
e
J. Chem. Soc., Chem., Commun., 1990, 795 & J.
Chem. Soc., Perkin Trans. 1, 1991, 1445 ©baboon™@flickr

3. how O
is the selectivity
achieved?
NH
OH N
H
(2 eq.)
MeLi, CuI
O
99% ee

4. chiral reagent
control
substrate
(achiral)
chiral
reagent
[ ]
substrate
(achiral)
chiral
reagent
chiral
product

5. problem
it is wasteful
©maol@flickr

6. H O
B
(+)-α-pinene 9-BBN•THF
of
synthesis
chiral
H
B
reagent
alpine borane

7. O
RL RS
H B O
B H RL
RS
with a
reduction H OH
chiral RL RS
reagent

8. O
RL RS
H B O
B H RL
RS
with a
reduction H OH
chiral RL RS
reagent

9. O
RL RS
H B O
B H RL
RS
with a
reduction H OH
chiral RL RS
reagent

10. (R)-fluoxetin
e
Prozac
J. Org. Chem., 1986, 51, 3394 &
J. Am. Chem. Soc., 1988, 110, 1539
CF3
O H
Me
N
H•HCl
©Touchstone Pictures

11. O
Cl
Cl Ipc
B O
H Ph
H
BCl
Cl
2
(+)-Ipc2BCl
H OH
synthesis
CF 3
Cl
using a chiral O H
Me
N
reagent
H•HCl ≥99% ee
1 recrystallisation

12. of
synthesis reagent
chiral
pinene

13. of
synthesis reagent
chiral
(+)-α-pinene
BH3
H
H 1. TMEDA H
2. BF3•OEt2
B BH2
H H H H
(–)-Ipc2BH (+)-IpcBH2

14. of
use boron reagents
chiral
H
H ii. H2O2 H OH
H NaOH
H
H H
B
98.4% ee
H H H

15. of
use boron reagents
chiral
Me
Me
ii. H2O2 H
H NaOH
H
HO
BH2 H
66% ee
H

16. of
use boron reagents
chiral
i. (–)-Ipc2BOTf
iPr2NEt OH O
O ii. RCHO
R

17. ©Brittany G@flickr

18. enolate
geometry
i. (–)-Ipc2BOTf
O iPr2NEt B
O
2

19. reagent chiral
B
O
control
2
H
O
H
OH
R
H
B
O or
H
O OH O
R
R

20. OH
O H
O
Me OH O O
H H
O Me
(–)-laulimali
de
fijianolide B
Org. Lett., 2001, 3, 3149
©luxpacis@flickr

21. chiral reagent control
OH
O H
O
OH O O
H H
O
(+)-Ipc2BO
CO2Me OTBS
H H H
O O O
OH OPMB
CO2Me
H H
OTBS O
H
H O
86%
O OPMB 62%de

22. organobora
nes ©Pierre J.@flickr

23. allylation with organoboranes
O
L L
R B
O
RZ
RZ
L R
B RE
RE
L
L L
OH H2O2 B
NaOH O
R
RZ RE R
RZ RE

24. stereospecific
O
L L
R B
O
RZ
RZ
L R
B RE
RE
L
L L
OH H2O2 B
NaOH O
R
RZ RE R
RZ RE

25. stereospecific
H L H L
R H
B B
L vs L
RE RE
O O
H R
RZ RZ

26. stereospecific
H L H L
R H
B B
L vs L
RE RE
O O
H R
RZ RZ

27. stereospecific
H L H L
R H
B B
L vs L
RE RE
O O
H R
RZ RZ
H
OH H
R RE
OH
RZ RE R
RZ

28. synthesis
BH3•SMe2 BOMe
MeOH
2
MgBr K
BF3•OEt2
B B
2 2

29. chiral reagent control
OH
B O
Et
Et H
2
92% ee

30. chiral reagent control
OH
B O
Et
Et H
2
92% ee
H
H H
B OH
Et
H
O
Et

31. chiral reagent control
CO2iPr OH
O
O
t-Bu
B CO2iPr t-Bu H
O
82% ee

32. chiral reagent control
CO2iPr OH
O
O
t-Bu
B CO2iPr t-Bu H
O
82% ee
H2O2
NaOH
CO2iPr CO2iPr
O O
H CO2iPr H CO2iPr
B B
O O
O O
t-Bu t-Bu
H H

33. OH
O
O O OH
CO2H
O
O
NaO2C
OH O O
O
HO
(+)-SCH351448
Org. Lett., 2005, 7, 3809
©Exothermic@flickr

34. chiral reagent control O
O O
OH
OH
CO2H
O
O
NaO2C
OH O O
O
HO
OBn O
BnO2C
O H
OBn OH
DCM, 0°C
Ar BnO2C
80% O
N 95% d.e.
Si
N Cl
Ar