Biomedical Engineering Reference
In-Depth Information
4.2.2 Phosphine Organocatalysis of Allenes with Azomethine Imines
Azomethine imines
15
are readily accessible, stable compounds that have been
employed recently as efficient 1,3-dipoles in various metal-catalyzed and organocat-
alytic cycloadditions [76-78]. To expand the scope of our phosphine-catalyzed annu-
lations of allenes, we tested azomethine imines as the reaction partners. To our
delight, the phosphine-catalyzed [3
3] annulations
of azomethine imines and allenoates produced unusual dinitrogen-fused heterocycles
with seven distinctive scaffolds, including tetrahydropyrazolopyrazolones, tetrahy-
dropyrazolopyridazinones, tetrahydropyrazolodiazepinones, and tetrahydropyrazolo-
diazocinones (Scheme 4.5) [48]. The reaction outcome depends on the structure and
chemical properties of the allenoates and the nature of the phosphine catalyst.
The [3
+
2], [3
+
3], [4
+
3], and [3
+
2
+
2] annulation occurred when we used an azomethine imine
15a
as the
electrophilic partner with
+
-methyl allenoate
7a
in the presence of a trialkylphosphine
(20 mol%). The first step in the mechanism proposed (Scheme 4.6) is the nucleophilic
addition of tributylphosphine to the allenoate
7a
to give the zwitterion
11
. The addition
of
11
to the azomethine imine
15a
generates the intermediate
23
, the conjugate
addition of which would yield the final product
16a
through the release of PBu
3
from
the intermediate
24
.
Azomethine imines readily served as a 1,3-dipole synthon in this annulation. Under
optimized conditions, a variety of aryl or alkyl azomethine imines underwent [3
+
2]
annulation, providing the anticipated products in moderate to excellent yields as
single
E
-isomers. Both
-alkyl- and
-aryl-substituted allenoates were amenable to
the [3
2] annulation, providing the corresponding tetrahydropyrazolopyrazolones
in excellent yields (Scheme 4.7 and Table 4.3).
+
O
O
R'
N
N
N
N
CO
2
Et
R
R
[3+2]
16
O
[3+3]
17
CO
2
Et
O
N
O
N
[3+2+3]
[3+3]
N
R'
NN
N
R
R
15
CO
2
Et
[3+3]
R
EtO
2
C
[4+3]
[3+2+3]
O
O
18
CO
2
Et
22
O
N
N
N
N
N
N
R
R
CO
2
Et
R
CO
2
Et
CO
2
Et
EtO
2
C
19
CO
2
Et
21
EtO
2
C
20
SCHEME 4.5
Phosphine-catalyzed [3
+
n
] annulations with azomethine imines. (Adapted
from [48], with permission; copyright
C
2011 American Chemical Society.)
