Improved Methodology for the Preparation of Chiral Amines

have to be faster than that of the other, resulting in an enantiomerically enriched product
which is another successful example of a dynamic kinetic resolution process. [60]
He reported high enantioselectivities for the reductive amination of hydratopicaldehyde with
p-anisidine in the presence of Hantzsch ester and phosphoric acid catalyst 9. [61] List
demonstrated that racemic aldehydes could be successfully converted to branched-chain
secondary amines in an excellent enantiomeric excess. He found that the use of a highly
hindered phosphate catalyst was essential, and intriguingly the best results required the very
specific use of a particular Hantzsch ester, in this case (Scheme 3.20).
O H 2 NR 3
R 1 R 2
[H]
O
R 1
H H 2 NR 3
R 2 [H]
NHR 3
R 1
∗R 2
α-branched chiral amines
R 1 ∗
β-branched chiral amines
NHR 3
R 2
R 1
R 2
O
H
+H 2 NR 3
-H 2 O
R 1
R 3
N
R 3
HN
H
R 1
H
R 2
R 2
racemization
R 3
N
R 1
R 2
H
H
N
H
HX*
R 3
N
R 1
R 2
H
R 1
NHR 3
R 2
EtOOC
COOEt
EtOOC
COOEt
N
R CHO 9(5mol%),MS5Å,C 6 H 6 ,6 o 1 C, 72 h R 1
NHR 3
R 2 R 2
EtOOC
COOEt
N
H
(1.2 equiv)
F
NHPMP
NHPMP
NHPMP
NHPMP
87%, 96% ee
88%, 98% ee
89%, 94% ee
92%, 98% ee
NHPh
NHPMP
78%, 94% ee 77%, 80% ee
Scheme 3.20. Asymmetric Reductive Amination of Aldehydes.
70