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R
2
R
2
O
*RO
N
N
P
OH
*RO
O
R
1
H
R
1
O
O
OH
*RO
R
2
H
P
AcOH
N
O
*RO
R
1
H
Figure 3.7.
Cooperative Br ø nsted acid catalysis.
PMP
PMP
EtO
2
C
CO
2
Et
N
HN
+
R'
Me
R'
Me
H
(1.0 eq)
(1.4 eq)
Rueping
List
ent
-PA
1i
(1 mol %)
Toluene, 35°C
80-98% yield
80-93% ee
PA
1f
(20 mol %)
Benzene, 60°C
46-91% yield
68-84% ee
Scheme 3.42.
R
1
EtO
2
C
CO
2
Et
O
PA
1n
(10 mol %)
HN
+
H
2
N
+
R
1
40-50°C, MS 5A
R
H
R
Benzene
R = alkyl or aryl
24 examples
49-92% yield
81-97% ee
Scheme 3.43.
reactions starting from ketones, amine, and Hantzsch ester proceeded in the presence
of 5Å MS to give secondary amines with excellent enantioselectivities. This method can
be applied to methyl aryl ketones as well as methyl alkyl ketones. Interestingly, the
reductive aminated product of even methyl ethyl ketone was obtained in 83% ee
(Scheme 3.43 ).
Following these initial studies, Rueping et al. further expanded this protocol to the
reduction of a wide range of heterocycles [73-75]: benzoxaxines, benzothiazines, ben-
zoxazinones, pyridines, and quinolines. Reduction of benzoxazines, in particular, is
highly effi cient, lowering the catalyst loading of PA
1k
to 0.1 mol % without considerable
loss in reactivity and selectivity [73]. Furthermore, they applied these methodologies to
