Fundamentals of Medicinal Chemistry

Overall reaction:

(a)

Overall reaction:

(b)

CH 3 CH=CHCH 3

but-2-ene

but-2-ene

CH 3 CH=CHCH 3

OsO 4 /H 2 O CH

3 CHOHCHOHCH 3

(±) 2,3-dihydroxybutane (racemate)

O

C C

H

H

O

Os

O O

Os

O

C C

H

H

O

O O HO

HO

C C

H

H

OH

OH

C C

H

H

(±) 2,3-dihydroxybutane

(racemate)

+

OsO 4

OsO 4

H 2 O

H 2 O

CH 3 H

CH 3

CH 3

CH 3

H

Br+

Br−

Br−

Br+

C C

H

H

C C

C C

Br

CH 3 Br

CH 3

H

H

Meso-2, 3-dibromobutane

CH 3 CHBrCHBrCH 3

Meso-2,3-dibromobutane

The bromine can approach

from either side

The osmium tetroxide can

approach from either side

Br 2

Br 2

Br 2

CH 3 H

CH 3

CH 3

CH 3

CH 3

CH 3

CH 3

CH 3

CH 3

CH 3

H

C=C

CH 3 H

H CH 3

C=C

Figure 10.5 Examples of the effect of the nature of a reagent on the stereochemistry of a

reaction. In both examples the reagent has an equal chance of attacking the C¼C from either side

P

C C

H

O

Fe

Fe

CO

P CO

PhPh Ph

Ph

CC

H

Li

−O CH 3 CH 3

tBuSCH

2 −−Br

tBuSCH

2

Various

steps

S,S-Captopril

Various
steps

• 
  

Unhindered reaction can only occur

from the near side of the C=C NewS configuration chiral centre

Figure 10.6 Stereoselective alkylation of an enolate in the synthesis of captopril. The heavier

straight lines are bonds in the plane of the paper while the thin straight lines, are bonds behind the

plane of the paper. The shape of the substrate means that an unhindered approach of the tertiary

butylthiomethyl bromide (tBuSCH 2 Br) is only possible from one side of the iron-complex sub-

strate. Consequently, reaction occurs mainly from this side of the complex, which results mainly in

a product with an S configuration

ASYMMETRY IN SYNTHESES 209