lecture4: 123.702
DESCRIPTION
Use of stoichiometric amounts of a chiral source. The usual suspects will be discussed, including borane reagents (mostly pinene derivatives) and the Brown allylation.TRANSCRIPT
chiral reagents gareth j rowlands
LECTURE FOUR
©baboon™@flickr
O
(R)-muscone J. Chem. Soc., Chem., Commun., 1990, 795 & J.
Chem. Soc., Perkin Trans. 1, 1991, 1445
O
OHNH
NH
(2 eq.)MeLi, CuI
O
99% ee
howis the selectivity
achieved?
substrate(achiral) chiral
reagent
controlchiral reagent
chiralproduct
substrate(achiral)
chiral reagent
[ ]
problemit is wasteful
©maol@flickr
BH O
(+)-α-pinene 9-BBN•THF
B
alpine borane
Hsynthesis of
chiralreagent
chiral
RL RS
O
B OH
RSRL
RL RS
OHH
BH
reduction with a
reagent
chiral
RL RS
O
B OH
RSRL
RL RS
OHH
BH
reduction with a
reagent
chiral
RL RS
O
B OH
RSRL
RL RS
OHH
BH
reduction with a
reagent
RL RS
O
B OH
RSRL
RL RS
OHH
BH
©Touchstone Pictures
NH•HCl
HO
CF3
Me
(R)-fluoxetineProzac
J. Org. Chem., 1986, 51, 3394 &J. Am. Chem. Soc., 1988, 110, 1539
reagent
synthesischiral
O
Cl
Cl
OHH
B OH Ph
ClIpc
Cl
HBCl
2(+)-Ipc2BCl
≥99% ee1 recrystallisation
using aNH•HCl
HO
CF3
Me
reagentsynthesis of
chiral
pinene
reagentsynthesis of
chiral
HB
H
H
H
H HBH2
H1. TMEDA2. BF3•OEt2
BH3
(+)-α-pinene
(–)-Ipc2BH (+)-IpcBH2
boron reagentsuse of
chiral
OHH
H
H
98.4% ee
ii. H2O2 NaOH
H H
HB
H
H
H
H
boron reagentsuse of
chiral
Me
H H
HOH
Me
66% ee
ii. H2O2 NaOH
HBH2
H
boron reagentsuse of
chiral
O
i. (–)-Ipc2BOTfiPr2NEt
ii. RCHOO
R
OH
©Brittany G@flickr
B
2
OO
i. (–)-Ipc2BOTfiPr2NEt
enolategeometry
O B
OH
H
R
OHO
H
R
H
B
2
O
O
R
OHor
controlreagent
chiral
©luxpacis@flickr
O
OH O O
O
Me
HOH
HHMe
O
Org. Lett., 2001, 3, 3149
fijianolide B
(–)-laulimalide
OCO2MeHH
(+)-Ipc2BO
H O
O
HOTBS
OPMB
O
OHCO2MeOPMB
OH
OTBS
HH
O
86%62%de
chiral reagent controlO
OH O O
OH
OH
HH
O
organoboranes ©Pierre J.@flickr
R
O
B RE
RZ
L
L
OB
RRZ
RE
L L
R
OB
RZ RE
L LH2O2NaOH
R
OH
RZ RE
allylation with organoboranes
R
O
B RE
RZ
L
L
OB
RRZ
RE
L L
R
OB
RZ RE
L LH2O2NaOH
R
OH
RZ RE
stereospecific
stereospecificH
B
OL
RER
RZ
L
B
OL
REH
RZ
H L
H R
vs
stereospecificH
B
OL
RER
RZ
L
B
OL
REH
RZ
H L
H R
vs
H
B
OL
RER
RZ
L
B
OL
REH
RZ
H L
H R
vs
OHREH
RZ
H
RR
OH
RERZ
stereospecific
BH3•SMe2MeOH BOMe
2
MgBr K
BF3•OEt2
B
2
B
2
synthesis
chiral reagent control
B
2
O
Et H Et
OH
92% ee
chiral reagent control
B
2
O
Et H Et
OH
92% ee
B
OH
H
Et
OHH
H
Et
chiral reagent control
BO
OCO2iPr
CO2iPr t-Bu
O
H t-Bu
OH
82% ee
chiral reagent control
BO
OCO2iPr
CO2iPr t-Bu
O
H t-Bu
OH
82% ee
B
O
H
H
t-Bu
O
O
CO2iPr
CO2iPrB
O
H
H
t-Bu
O
O
CO2iPr
CO2iPr
H2O2NaOH
©Exothermic@flickr
ONaO2C
OH O O
HO
O
OCO2H
OHOO
OH
O
Org. Lett., 2005, 7, 3809(+)-SCH351448
OBnO2C
OBn
H
O
NSi
N
Ar
Ar
Cl
OBnO2C
OBn OHDCM, 0°C
80%95% d.e.
chiral reagent controlO
NaO2COH O O
HO
O
OCO2H
OHOO
OH
O