Biomedical Engineering Reference
In-Depth Information
O
O
N
N
O
cat. PCy
3
N
N
•
+
CO Et
2
+
NN
0°C,120h
Ar
EtO
2
CO Et
2
Ar
EtO
2
CO Et
2
Ar
CH Cl /benzene 4:1
22
4a
15
25
26
SCHEME 4.9
Synthesis of highly functionalized tetrahydropyrazolodiazocinones. (Adapted
from [48], with permission; copyright
C
2011 American Chemical Society.)
TABLE 4.4 Highly Functionalized Tetrahydropyrazolodiazocinones
Entry
Ar
Yield (%)
25:26
1
Ph
81
34:66
2
4-Me-Ph
64
39 : 61
3
4-OMe-Ph
76
44 : 56
4
4-Br-Ph
77
29 : 71
5
3-NO
2
-Ph
77
17 : 83
6
2-Br-Ph
92
28 : 72
7
2-Cl-Ph
90
24 : 76
8
2-F-Ph
88
25 : 75
9
2-NO
2
-Ph
73
9 : 91
10
2-Naphthyl
76
32 : 68
2,3-butadienoates and electron-deficient olefins to form functionalized cyclopentenes
[79]. Unlike the reaction of allenoates with imines, the reaction of allenoates with
electron-deficient olefins typically furnishes a mixture of the two regioisomeric prod-
ucts
33
and
34
(Scheme 4.10).
To alleviate this regioscrambling, we explored the dipolar [3
2] cycloaddi-
tions of the allenoate
4a
and C2-symmetric cyclic electron-deficient olefins (e.g.,
maleimides). When we mixed
N
-phenylmaleimide with ethyl allenoate
4a
in the
presence of triphenylphosphine (10 mol%) in benzene at 60
◦
C, the reaction mixture
smoothly underwent the desired [3
+
2] annulation to form the bicyclic succinimide
36
in 99% isolated yield (Scheme 4.11).
To increase the versatility of the reaction and the diversity of the reaction products,
we also investigated the reactions of
+
-substituted allenoates with other maleimides.
CO Me
2
cat. PPh
3
benzene, rt
MeO
2
CO Et
2
CO Et
2
•
CO Et
2
+
4:1
+
CO Me
2
4a
32
33
34
SCHEME 4.10
Zhang and Lu's [3
+
2] annulation with an electron-deficient olefin.
