Improved Methodology for the Preparation of Chiral Amines

OH
N
O
R
1. 2LDA, LiCl
2. R 1 X
THF
OH
N
O
R 1
R
80-99% yield
94-99% de
OH
N
H 2 SO 4 dioxane
O
R
N BH 3 Li
R 1
THF
HO
O
R 1
R
HO
O
R
H
R 1
87-97% yield
95-97% ee
R 1
R
75-92% yield
90-98% ee
80-88% yield
88-99% ee
Scheme 1.6. Chiral Auxiliary Approach in Asymmetric Synthesis
The third approach which is the catalytic asymmetric transformation, is promoted by a chiral
entity which is generally used in a catalytic amount enhancing the economic value of the
process. The chiral entity can be chiral catalysts (e.g. chiral Lewis acid or base, chiral
organocatalysts, chiral organometallic complexes) or even bio catalysts. One of the most
fascinated examples was the synthesis of L-DOPA developed by Knowles. [36]
AcO
H
OMe
COOH [Rh(DiPAMP)]
NHAc H 2
AcO
H
OMe
H
COOH
NHAc
H 3 O +
AcO
H
OMe
H
L-DOPA
97.5% ee
COOH
NH 2
CH 3 O
P
P
OCH 3
Scheme 1.7. Synthesis of L-DOPA
Another example showing the importance of this approach, was developed by Royoji
Noyori, [37] In 1980 he developed different derivatives of chiral BINAP ligands which were
widely used as chiral ligands for Ru and Rh hydrogenation reactions. He was successful in
applying his catalytic system on industrial scale for the (-)-menthol synthesis from myrcene.
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