Fundamentals of Medicinal Chemistry

HO

H +N

H

CF 3

Br−

Cl O

Cl

CH 3 O

CH 3 Cl/PhCH 3 /NaOH

Cl O

Cl

H CH 3 O CH^3

(1)

This starting compound is
produced in the form of a
racemate
Catalyst

92% e.e.

Indacrinone

(a diuretic)

Various steps

New

S chiral

centre

(a)

An example of the type of

catalyst used in these

conversions

Ph Ph

tBu tBu

N N

O O

Mn 1R,2S-(+) 78% e.e.O

O

(+) 67% e.e.

O

R-(+) 57% e.e.

O

1R, 2S-(−) 59% e.e.

(+)-Diethyl tartrate (−)-Diethyl tartrate

C C

R^2

R^3 R^1

O CH 2 OH

Ti(OiPr) 4

tBuOOH

CH 2 Cl 2

Ti(OiPr) 4

tBuOOH

CH 2 Cl 2

(c)

CH 2 OH CH 2 OH

R^3

R^3

R^1

R^1

R^2 R^2

CC

O

C C

(b)

Figure 10.8 Examples of non-enzyme catalysed steroselective reactions with (a) a non-organo-

metallic catalyst, (b) an organometallic catalyst and (c) a Sharpless–Katsuki catalyst

Methods that do not use catalysts to produce stereoselectivity

These general approaches can be classified for convenience as:

1. using chiral building blocks,

2. using a chiral auxiliary and

3. using achiral substrates and reagents.

1. Using chiral building blocks. These methods depend on the use of building

blocks with the required configurations. A chiral building block whose struc-

ture contains the required configuration is reacted with a suitable substrate to

introduce the desired asymmetric centre into the product (Figure 10.9). The

ASYMMETRY IN SYNTHESES 211