Chemistry Reference
In-Depth Information
stereocenter (Scheme 2B.28) [75]. Deng and coworkers further hypothesized that, with
another catalyst presenting the hydrogen bond donor and acceptor in a different spatial
relationship, the relative orientation between the two prochiral substrates could be
altered [76]. In principle, such a catalyst could promote the reaction with a different
sense of diastereoselectivity. Indeed, they discovered that the 9-thiourea cinchona alka-
loid
103
afforded a sense of diastereoselectivity complementary to that by
76
[76] .
Consequently, these two types of bifunctional catalysts, both easily synthesized from
quinine and quinidine, enabled the one-step preparation of any of the four possible
stereoisomers of products
137
in a highly stereroselective fashion (Scheme 2B.29) [76].
The synthetic application of such reactions was illustrated in the total syntheses of man-
zacidins A (
138
) and C (
139
) using the same route (Scheme 2B.29) [76].
Ar
S
NH
MeO
OH
Ar
NH
OR
HN
OMe
S
OH
N
N
HN
N
H
OR
N
H
CN
N
Cl
QD-2
N
QD-
1
X
H
N
+
R
H
N
CN
Q-2
O
Q-1
74,135
168
CN
Cl
CN
Cl
CN
Cl
CN
Cl
3
3
3
3
X
X
X
X
CN
CN
CN
CN
1
1
1
1
R
R
R
R
O
O
O
O
(
1S, 3S
)-
137
(
1R, 3R
)-
137
(
1R, 3S
)-
137
(
1S, 3R
)-
137
9:1-15:1 dr,
94-97% ee
98-99% yield
9:1-16:1 dr,
94-98% ee
97-99% yield
4:1-20:1 dr,
86-96% ee
71-98% yield
3:1-20:1 dr,
85-93% ee
45-95% yield
Br
CN
Cl
QD-76f
(20 mol %)
MeSOC
HN
N
CN
O
Toluene, rt
96 h
CN
H
CO
2
H
Me
COSMe
O
(
1R, 3R
)-
137
135
138
+
93% ee, 10:1 dr
71% yield
Manzacidin A
Br
Cl
QD-103
(10 mol %
)
Toluene, rt
12 h
CN
Cl
HN
N
CN
O
MeSOC
CN
136
CO
2
H
H
Me
(
1R, 3S
)-
137
O
139
96% ee, 9:1 dr
98% yield
Manzacidin C
Scheme 2B.29.
Deng and coworkers successfully extended such complete catalytic stereochemical
control to another distinct complex asymmetric transformation [47]. They observed that
the asymmetric Diels-Alder reactions of 2-pyrone
94a
with α - chloroacrylonitrile
136
preferred the formation of
endo
-
140
with the 6′ - OH cinchona alkaloid
76c
, but
exo
-
140
with the 9-thiourea cinchona alkaloid
103
(Scheme 2B.30). These results support the
notion that manipulations of acid-base bifunctional catalysts could potentially provide
a generally applicable means for establishing catalytic control of diastereoselectivity in
complex asymmetric reactions.
