6
756
C. D. Rosa et al. / Tetrahedron Letters 52 (2011) 6754–6757
Table 4
Local electrophilicity (
3
. Theoretical studies
k
x , in eV) of nitripirroles 1a and 1b, and local nucleophilicity
(N
k
, in eV) of butadienes 2–4
Studies carried out in Diels–Alder reactions have shown that the
x
k
N
k
reactivity indices defined within the conceptual DFT are powerful
tools for establishing the polar character of such reactions. The
static global properties of N-tosylnitropirroles 1a and 1b, and the
7
1a
C1
C2
C3
C4
C1
C2
C3
C4
0.12
0.19
0.02
0.23
0.12
0.04
0.00
0.02
2
3
4
C1
C4
C1
C4
C1
C4
1.11
0.80
0.80
0.97
0.56
1.47
butadienes 2–4, namely electronic chemical potential (
hardness ( ), global electrophilicity ( ), and global nucleophilicity
N), are shown in Table 3.
l), chemical
g
x
1b
(
The electronic chemical potential of N-tosylnitropirroles,
= 4.61 eV (1a) and 4.54 eV (1b), is lower than that of butadienes
l
2
–4,
l
range from ꢀ3.30 to 2.69 eV. Therefore, it is expected that
along a polar D–A reaction, the charge transfer (CT) will take place
from the electron-rich dienes to nitropirroles.
Table 5
Global electrophilicity (
roles 1a and 1b, in different solvents
The electrophilicity
.14 eV (1b), allows for the classification of this species as a strong
electrophile within the electrophilicity scale. On the other hand,
they present a low nucleophilicity N values, 2.21 eV (1a) and
x
of N-tosylnitropirroles, 2.31 eV (1a) and
x), in eV, of nitripir-
2
8
x
HCCl
2.74
2.57
3
2
.18 eV (1b), being classified also as a moderate nucleophile within
1a
9
the nucleophilicity scale.
The electrophilicity
.68 eV (4), and classifies them as marginal electrophiles in the
1b
x
of dienes is 0.94 eV (2), 0.73 eV (3) and
HMIN
6.93
6.75
EAN
7.92
7.68
1
1
a
b
0
electrophilicity scale. On the other hand, the nucleophilicity N of
these species are 2.94 eV (2), 3.67 eV (3) and 3.77 eV (4). Therefore,
while diene 2 is a moderate nucleophile, dienes 3 and 4 are strong
nucleophiles. As expected, presence of one or two strong electron-
releasing substituents in the diene system increases the nucleophi-
licity of 3 and 4. An analysis of the global reactivity indices
indicates that in a polar DA reaction, N-tosylnitropirroles will act
as a strong electrophile, while dienes 3 and 4 will act as a strong
nucleophile.
1a
1b
nitropirroles 1a and 1b in ca. 0.5 eV.12 A more drastic effect is
found in the nitropirroles-IL complexes where the electrophilcity
x
increases in the range from 4 to 5 eV. The more acidic IL EAN
produces the highest increase of the electrophilicity. Although
these values have to be carefully considered according to the sim-
plicity of the model, they indicate that using ILs as solvents will
accelerate polar DA reactions. This is a consequence of the increase
of the reaction’s polar character achieved by an increase of the
In a polar cycloaddition between asymmetrical reagents, the
most favorable two-center interaction will take place between
the more electrophilic center, characterized by the highest value
of the local electrophilicity index10
k
x at the electrophile, and
the more nucleophilic center, characterized by the highest value
7
of the local nucleophilicity index11
electrophilcity of N-tosylnitripirroles.
k
N at the nucleophile. The local
electrophilicity
k
x indices for nitropirroles 1a and 1b, and nucleo-
3
.1. Computational details
philicity N , indices for dienes 2–4 are presented in Table 4.
k
For N-tosyl-2-nitropirrole 1a, the more electrophilic centers are
C2 and C4, while for N-tosyl-3-nitropirrole 1b is the C1. As it is
expected, a change in the position of the nitro group in the pirrole
nucleous causes a change in the local reactivity of the pirrole
system.
For the diene 2, the most nucleophilic center corresponds with
the C1, NC1 = 1.11 eV, whereas for the dienes 3 and 4 the most
nucleophilic center corresponds with the C4. Consequently, a
change in regioselectivity is expected between diene 2 and dienes
DFT calculations were carried out using the B3LYP13 exchange-
⁄
correlation functionals, together with the standard 6-31G basis
1
4
set. All calculations were carried out with the Gaussian 09 suite
1
5
of programs.
The global electrophilicity index
1
6
x
is given by the following
), in terms of the electronic chemical
and the chemical hardness . Both quantities may be
approached in terms of the one electron energies of the frontier
molecular orbital HOMO and LUMO, and , as = ( )/2
) respectively. Recently, Domingo et al. have
2
simple expression.
potential
x = (l /2g
l
g
e
H
e
L
l
H L
e + e
3
and 4.
1
7
and
introduced an empirical (relative) nucleophilicity index N based
on the HOMO energies obtained within the Kohn-Sham scheme19
g
= (e
L
ꢀ
e
H
Finally, solvent effects of ILs in these Diels–Alder reactions were
18
estimated by a formation of a hydrogen-bonded complex between
the nitro oxygen atoms of pyrrole derivatives 1a and 1b, and the
most acidic hydrogen atom of solvent.12 The global electrophilicity
,
and defined as N = eHOMO(Nu) ꢀ eHOMO(TCE). The nucleophilicity is
referred to tetracyanoethylene (TCE), because it presents the low-
est HOMO energy in a large series of molecules already investi-
gated in the context of polar cycloadditions. This choice allows
us conveniently to handle a nucleophilicity scale of positive values.
x
of the corresponding hydrogen-bonded complexes are shown in
Table 5. Formation of a no-classic hydrogen bond between N-tosyl-
nitropirroles and chloroform increases the electrophilcity
x of the
1
0
11
Table 3
Local electrophilicity and nucleophilicity indices
were evaluated using the following expressions:
x
¼
k
and N
k
,
þ
Electronic chemical potential (
l
), chemical hardness (
g
), global electrophilicity (
x
),
x
k
xf
and
k
ꢀ
þ
ꢀ
and global nucleophilicity (N), in eV, of nitripirroles 1a and 1b, and butadienes 2–4
N
k
¼ Nf where fk and fk are the Fukui functions for a nucleophilic
k
2
0
l
g
x
N
and electrophilic attacks, respectively.
1
1
2
3
4
a
b
ꢀ4.61
ꢀ4.54
ꢀ3.30
ꢀ2.79
ꢀ2.69
4.60
4.80
5.77
5.33
5.31
2.31
2.14
0.94
0.73
0.68
2.21
2.18
2.94
3.67
3.77
4. Conclusions
It has been demonstrated that N-tosyl-nitropyrroles react effi-
ciently with the above-mentioned dienes in normal electron