Improved Methodology for the Preparation of Chiral Amines

(S)-(α)-Methylbenzylamine and its enantiomer (R), appear to be ideal compounds as chiral
auxiliaries or chiral building blocks for pharmaceutical and chemical industry. (S) and (R)
enantiomers are inexpensively available in very high enantiomeric purity, which makes them
attractive as stereodifferentiating agents even for industrial scale operations. [51]
It has been used in the synthesis of biologically active molecules such as Labetalol (βblocker)
and Tamsulosin. [52] Another example is α-amino acids, eg; proline. Proline has a
unique value in asymmetric processes; it is used as a ligand in transition metal-catalysis. [53]
Recently proline and its derivatives were applied as highly efficient organocatalysts in
different organic transformation as asymmetric Aldol, [54] Mannich [55] and Michael
reactions. [56]
Another important class of chiral α-chiral amines which are used in synthesis of
pharmaceutical building blocks is the quinuclidine family. An example of this class includes
enantiopure 3-aminoquinuclidine, an important intermediate in the synthesis of 5-HT 3
serotonin ligands, [57] such as zacopride. Also diamines as (1S,2S)-Cyclohexane-1,2-diamine is
used as chemotherapeutic agents, [58] chiral auxiliary, transition metal-catalysis and in
organocatalysis. [59] Of course there are more examples of the available chiral amines which
are used in pharmaceutical and agrochemical industry with great success for synthesis of
natural products and drugs. [60] The following figure shows some examples of drugs having
chiral amines(figure 1.7).
HO
N
N
H
(S)-repaglinide
(hypoglycemic agent)
HO
CONH 2
H
N
Labetalol
(β−blocker)
H
Figure 1.7. Examples of Drugs with α-Chiral Amines.
21
Ph
Ph
O
O
OH
MeO
O
NH
O
HO
NH 2
H
N
O
O
amoxicillin
(antibiotic)
SO 2 NH 2
N
H
O
HCl
AcO O OH
HO O
AcO
H
HO OBz
Taxol
(anticancer drug)
H H
S
O
COOH
OEt
(R)-tamsulsin hydrochloride
(benign prostatic hyperplasia)
Cl
H 2 N
H
N
N
O
O
COOMe
H
Ph
rivastigmine
(Alzheimer)
O
N
H
OMe
NMe 2
N
(S)-zacopride
(5-HT 3 agonist)
Ritalin
(treatment of hyperdeficit disorder)