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