Biomedical Engineering Reference
In-Depth Information
O
O
N
N
O
cat. PC
y
3
N
N
•
CO Et
2
+
N
N
0°C,72h
+
15a
Ar
EtO
2
CO Et
2
Ar
EtO
2
CO Et
2
Ar
4a
CH Cl /benzene 4:1
22
Ar =
p
-NO C H
26 4
25a
26a
O
PCy
3
isomerization
N
N
CO Et
2
Ar
EtO
2
CO Et
2
PCy
3
31
27
O
O
PCy
3
-
+
N
N
CO Et
2
PCy
3
PCy
3
N
N
15a
Cy
3
Ar
EtO
2
CO Et
2
Ar
EtO
2
CO Et
2
CO Et
2
28
29
30
SCHEME 4.8
Phosphine-catalyzed [3
+
2
+
3] annulations with azomethine imines.
3] annulation occurred when we reacted the azomethine imines
15a
with ethyl 2,3-butadienoate
4a
in the presence of PCy
3
(20 mol%). In the mechanism
proposed (Scheme 4.8), the key event is the formation of the trimeric zwitterionic
intermediate
28
, which is generated through the conjugate addition of the phospho-
nium dienolate
27
to another molecule of the allenoate
4a
. With the introduction of
the azomethine imine
15a
, the intermediate
28
generates
29
, which gives compound
31
after cyclization, proton transfer, and phosphine elimination. The isomerization of
the olefin unit in intermediate
31
yields the final products
25a
and
26a
as a mixture of
tautomers. The trimeric zwitterionic intermediate, which forms from two molecules
of ethyl 2,3-butadienoate and a molecule of phosphine, acts as a 1,5-dipole in the
cycloaddition reaction. We employed a mixed solvent of CH
2
Cl
2
and benzene for
the [3
The [3
+
2
+
3] annulation because CH
2
Cl
2
aids dissolution of the azomethine imine
and benzene favors formation of the trimeric zwitterionic intermediate
28
.
Under the optimized reaction conditions, both electron-rich and electron-deficient
aryl azomethine imines, as well as a polyaromatic azomethine imine, were compat-
ible substrates. Among the many azomethine imine substrates tested, 2-halophenyl
azomethine imines provided higher yields, and 2-nitrophenyl azomethine imine gave
a better ratio of one isomer over the other (Scheme 4.9 and Table 4.4).
+
2
+
4.2.3 Phosphine Organocatalysis of Allenes with Electron-Deficient Olefins
4.2.3.1
2] Annulation with Maleimides to Form Bicyclic Succinimides
In 1995, Zhang and Lu described the phosphine-catalyzed [3
[3
+
+
2] annulation of
