A theoretical and experimental study of the polar Diels - Alder cycloaddition of cyclopentadiene with nitrobenzodifuroxan

Article abstract of DOI:10.1002/poc.1469

The mechanism of the Diels-Alder interaction of 4-nitrobenzodifuroxan (NBDF) with cyclopentadiene (Cp), resulting in the highly stereoselective formation of the stable endo [2+4] adduct has been elucidated by combining density functional theory (DFT) and experimental studies. Calculations at the B3LYP/6-31G^* level reveal that this adduct does not derive from a direct normal electron demand cycloaddition process. Instead, the evidence is that the interaction proceeds initially through a very polar inverse electron demand process to afford the intermediate [4+2] cycloadduct. Then, this species undergoes a complete conversion into the more stable isomeric endo [2+4] adduct via a [3+3] Claisen-type sigmatropic shift. The lifetime of the [4+2] intermediate was sufficient to allow its full ¹H NMR characterization at S 10°C. Viewing the results in the general context of the Diels-Alder reactivity of nitrobenzofur-oxans, a noteworthy feature is that the similar behavior of NBDF and 4-aza-6-nitrobenzofuroxan (ANBF) goes along with a similar positioning of the two compounds on the general electrophilicity scale of Parr et al. Copyright

Full text of DOI:10.1002/poc.1469

Research Article
Received: 16 June 2008,
Revised: 29 September 2008,
Accepted: 3 October 2008,
Published online in Wiley InterScience: 26 November 2008
(
www.interscience.wiley.com) DOI 10.1002/poc.1469
A theoretical and experimental study of the
polar Diels–Alder cycloaddition of
cyclopentadiene with nitrobenzodifuroxan
a
a
a
Dmitry V. Steglenko , Mikhail E. Kletsky , Sergey V. Kurbatov ,
a
a
b
Artem V. Tatarov , Vladimir I. Minkin *, R e´ gis Goumont *
b
*
and Fran c¸ ois Terrier
The mechanism of the Diels–Alder interaction of 4-nitrobenzodifuroxan (NBDF) with cyclopentadiene (Cp), resulting
in the highly stereoselective formation of the stable endo [2R4] adduct has been elucidated by combining density
functional theory (DFT) and experimental studies. Calculations at the B3LYP/6-31G* level reveal that this adduct does
not derive from a direct normal electron demand cycloaddition process. Instead, the evidence is that the interaction
proceeds initially through a very polar inverse electron demand process to afford the intermediate [4R2] cycloadduct.
Then, this species undergoes a complete conversion into the more stable isomeric endo [2R4] adduct via a [3R3]
1
Claisen-type sigmatropic shift. The lifetime of the [4R2] intermediate was sufficient to allow its full H NMR
characterization at S10 -C. Viewing the results in the general context of the Diels–Alder reactivity of nitrobenzofur-
oxans, a noteworthy feature is that the similar behavior of NBDF and 4-aza-6-nitrobenzofuroxan (ANBF) goes along
with a similar positioning of the two compounds on the general electrophilicity scale of Parr et al. Copyright ß 2008
John Wiley & Sons, Ltd.
Supporting information may be found in the online version of this article.
Keywords: polar Diels–Alder cycloaddition; superelectrophilic olefins; nucleophile–electrophile combination; nitrobenzo-
furoxans; DFT calculations
stereoselective NED and IED adducts, i.e. the [2þ4] and [4þ2]
INTRODUCTION
[
37]
adducts 5 and 6, respectively.
Because the remaining
The high susceptibility of nitro-substituted 2,1,3-benzoxadiazoles
and related 10-p-electron heteroaromatic substrates to undergo
covalent nucleophilic addition or substitution processes has long
nitroolefinic fragment of the monoadduct 6 is also very reactive,
diadduct formation subsequently occurs, proceeding with high
stereoselectivity to give the highly functionalized structure 7 as
[
1–25]
[37]
attracted considerable attention.
thermodynamic reactivity for these Meisenheimer electrophiles
is nicely provided by a comparison of the pK values for water
addition. The pK values for hydration of the prototype
,6-dinitrobenzofuroxan (DNBF, 1) and 4-aza-6-nitrobenzofur-
Quantitative evaluation of
the thermodynamically stable product of the reaction.
The
reaction of ANBF with Cp has also been studied, yielding a
mixture of the two [2þ4] and [4þ2] monoadducts 8 and 9 at
ꢀ20 8C. Raising the temperature to 0 8C led to conversion of 9
a
a
[
26]
4
into the more stable adduct 8 (Scheme 2).
oxan (ANBF, 2) structures to yield the s-complexes C-1 and C-2
are 3.75 and 4.06, respectively, in aqueous solution, as compared
Density functional theory (DFT) calculations have been
recently carried out which have fully confirmed the reactivity
[
43,44]
with a pK value of 13.43 for formation of the analogous adduct
patterns depicted in Schemes 1 and 2.
More importantly,
a
[
8,26,27]
C-3 of 1,3,5-trinitrobenzene (TNB, 3).
Based on these
however, these calculations have demonstrated that the
formation of the [2þ4] and [4þ2] DNBF adducts 5 and 6
proceeds through the initial formation of the zwitterionic
figures, neutral compounds such as 1 and 2 have been accorded
[
26,27]
superelectrophilic properties.
This has led to numerous
[
10,11,28–33]
synthetic, analytical and biological applications.
Of equal interest, however is that compounds like 1 and 2 have
also been found to undergo a variety of Diels–Alder reactions, a
behavior which is in itself evidence that the six-membered ring of
these superelectrophilic heterocycles has a poor aromatic
*
Correspondence to: R. Goumont, Institut Lavoisier de Versailles (ILV), UMR
180, University of Versailles, 45 Etats-Unis Ave., 78035 Versailles Cedex, France.
8
[
26,34–39]
E-mail: goumont@chimie.uvsq.fr
character relative to TNB.
As illustrated in Scheme 1, DNBF can formally behave as do
a
D. V. Steglenko, M. E. Kletsky, S. V. Kurbatov, A. V. Tatarov, V. I. Minkin
Department of Chemistry, Southern Federal University, 7 Zorge St., 344090
Rostov-on-Don, Russian Federation
[
40,41]
nitroalkenes,
being susceptible to act as a dienophile in
normal electron-demand (NED) Diels–Alder reactions as well as a
heterodiene in inverse electron-demand (IED) Diels–Alder
b
R. Goumont, F. Terrier
[
42,43]
reactions.
In Scheme 1, the reaction of DNBF with
Institut Lavoisier de Versailles (ILV), UMR 8180, University of Versailles, 45
Etats-Unis Ave., 78035 Versailles Cedex, France
cyclopentadiene (Cp) affords initially a mixture of the two
J. Phys. Org. Chem. 2009, 22 298–307
Copyright ß 2008 John Wiley & Sons, Ltd.

POLAR DIELS–ALDER CYCLOADDITION
Scheme 1.
[
43]
intermediate 4. Similarly, the formation of the diadduct 7 from
the monoadduct 6 also involves the formation of a zwitterion.
Contrasting with the results for DNBF, no zwitterionic intermedi-
ate of sufficient stability, i.e. 10, could be identified on the
reaction coordinate pertaining to the formation of the ANBF
Recently, we have shown that the dual superelectrophilic and
Diels–Alder reactivity extends to the single nitroolefinic
fragment of the 4-nitrobenzodifuroxan (NBDF, 11) mol-
[
45,46]
ecule.
Thus, the reaction of NBDF with Cp proceeds very
readily in chloroform to give the endo [2þ4] adduct 12 whose
[
44]
[45,46]
monoadducts 8 and 9.
The interaction proceeds through a
structure has been confirmed by X-ray crystallography.
very polar transition state to give the [4þ2] adduct 9 which is
An interesting feature, however is that the nitroolefinic
fragments of NBDF and ANBF have similar electrophilicities,
as measured by the values of the global electrophilicity index,
subsequently converted into the more stable [2þ4] isomer 8 via a
[
44]
[
3þ3] Claisen-type sigmatropic shift.
[
47]
v, introduced by Parr.
The question was therefore posed of
whether the isolated NBDF adduct 12 was formed directly
through either a zwitterionic intermediate, i.e. 14, or a strongly
polar transition state, or was the result of a sigmatropic
rearrangement of the so far undetected [4þ2] isomer 13
(
Scheme 3). We report here the results of a DFT study of the
NBDF/Cp system which was carried out using the same
calculations strategy as that developed by Domingo et al. for
[
43,44]
the DNBF/Cp and ANBF/Cp systems.
Based on the results
obtained, an experimental reinvestigation of the NBDF
reactivity has been carried out which has allowed the NMR
identification of 13 as a transient adduct along the reaction
coordinate.
As recall by a referee, strong polar Diels–Alder reactions are
governed by charge transfer processes and not by molecular
orbital interactions, so that the use of the NED and IED terms to
classify the [2þ4] and [4þ2] adducts identified in the present
work is not conceptually correct. Referring to this formalism is
useful, however, and here helpful to correlate our results with
Scheme 2.
J. Phys. Org. Chem. 2009, 22 298–307
Copyright ß 2008 John Wiley & Sons, Ltd.
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D. V. STEGLENKO ET AL.
Scheme 3.
those obtained in previously reported studies of the Diels–Alder
reactivity of DNBF.
its maximum value, i.e. at the most reactive site of the
[
63]
electrophile. Calculated v values for NBDF are given in Fig. 1.
k
2
m
v ¼ 2h
(1)
RESULTS AND DISCUSSION
m
h
DNmax ¼ ꢀ
(2)
(3)
Computational methods and reactivity indexes
vk ¼ vfþ
Calculations based on the method of DFT were performed using
k
[
48,49]
the B3LYP exchange correlation functional,
together with
[
50]
the standard 6-31G* basis set, as developed by Domingo et al.
Global and local electrophilicity analysis
Recent investigations have used the v values to classify dienes
[
44]
for the DNBF/Cp and ANBF/Cp interactions.
Full geometry
optimization was achieved by the Berny analytical gradient
[
51,52]
[43,44,61–63,66,67]
optimization method.
The stationary points were charac-
and dienophiles on a unique scale.
According to
terized by frequency calculations in order to ascertain that the
transition state structures are associated with only one imaginary
frequency. Minimum energy reactions paths (MERPs) were
determined by gradient scanning from the transition state (TS)
structures in both direct and reverse directions of the transition
this model, the polar character of a Diels–Alder interaction can be
assessed from the difference, Dv, in the global electrophilicities
of the two reagents as well as the DNmax values for the system at
hand. Thus, it can be safely anticipated that reactions involving a
diene and a dienophile located at the ends of the v scale will
[
53]
[61–63,66]
vector. NBO (Natural Bond Orbital) analysis was performed for
proceed with an especially strong polar character.
In turn,
[
54,55]
all stationary points.
reactions associated with small Dv values should be prototypes
[
61–63,66]
With dichloromethane as a reference (e ¼ 8.93), solvent effects
of non-polar processes.
At the same time, consideration
were considered for all stationary points on the basis of the
of the local electrophilicity indexes has proved to be useful to
account for the regioselectivity in DA (Diels-Alder) reactions
[
56–59]
polarizable continuum model (PCM) of Tomasi et al.
All
[
43,44,61–63]
computations were carried out with the Gaussian 03 suite of
exhibiting a polar character.
[
60]
programs.
With v values ꢁ4.8, NBDF, ANBF, and DNBF correspond to the
most electrophilic compounds so far ranked on the v scale
(Table 1). As a result, their reactions with Cp, and most other
dienic structures, are characterized with large Dv values. This
leaves no doubt that the related cycloadditions will exhibit a large
polar character. For comparison, it is only in the presence of a
Lewis acid catalyst that the electrophilicity of nitroethylene
becomes associated with a high v value, for example v ¼ 4.33 for
Recent studies have shown that some reactivity indexes can be
defined within the DFT theory which are very useful for
predicting the feasibility as well as the more or less polar
[
43,44,61–63]
character of Diels–Alder reactions.
These include the
global electrophilicity index, v, introduced by Parr and defined by
[
47,64,65]
Eqn 1.
In this equation, the electronic chemical potential m
and the chemical hardness h of a substrate are two parameters
which were evaluated in terms of the one-electron energies of
the frontier molecular orbitals (FMOs) ie; the Highest Occupied
Molecular Orbit (HOMO) and the Lowest unoccupied Molecular
Orbital (LUMO) at the ground state of the molecules:
the nitroethylene /BH complex, making it possible to engage this
3
attractive nitroolefin in many C—C coupling reactions, including
[
40–42,61–63,68–72]
strongly polar Diels–Alder reactions.
Similarly,
appropriate Lewis acid catalysts have to be employed to enhance
the electrophilicity of nitro-activated olefins such as trans-
b-nitrostyrene and 1,1-dinitro-2,2-diphenylethylene as well as of
cyano- and carbonyl-activated olefins, e.g. benzylidenemaloni-
trile, which have v values comparable to that of nitroethy-
[
47,64,65]
m ¼ ½(e
H
þ e
L
); h ¼ (e
L
ꢀ e
H
).
Another informative index
used by Domingo et al. is the so called DNmax parameter, defined
by Eqn (2), which is a measure of the maximum amount of
[
47]
electronic charge that the electrophilic partner can accept.
[
73,74]
Calculated values v, m, h, and DNmax of relevance for our study are
lene.
collected in Table 1. Also important is the local electrophilicity
The large polar character predicted by the v values for the
index (v ) defined by Eqn (3) which shows that the electrophilic
Diels–Alder reactions implying DNBF, ANBF, and NBDF implies the
k
character of a molecule will develop to the greatest extent at the
regiochemistry of the cycloadditions be determined by the local
þ
[43,44]
site where the Fukui function for nucleophilic attacks (f ) displays
electrophilicities, as measured by v
k
.
As a matter of fact, the
k
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Copyright ß 2008 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2009, 22 298–307

POLAR DIELS–ALDER CYCLOADDITION
Table 1. Electronic chemical potential m, chemical hardness h, global electrophilicity v, and DNmax parameter for dienophiles and
a
dienes discussed in this work
Olefin-type compound
m
h
v
DNmax
b
DNBF
ꢀ0.2177
ꢀ0.2084
ꢀ0.2144
ꢀ0.2046
ꢀ0.1835
ꢀ0.1832
ꢀ0.1759
ꢀ0.1958
ꢀ0.1211
ꢀ0.1212
ꢀ0.1106
0.1180
0.1229
0.1300
0.1316
0.1439
0.1529
0.1582
0.2001
0.2074
0.2120
0.2016
5.46
4.81
4.80
4.33
3.16
2.99
2.70
2.61
0.97
0.94
0.83
1.84
1.69
1.65
1.55
1.27
1.20
1.11
0.98
0.58
0.57
0.55
c
ANBF
NBDF
Nitroethylene / BH3
d
e
f
1
,1-Dinitro-2,2-diphenylethylene
Benzylidenemalonitrile
Trans-b-nitrostyrene
Nitroethylene
,3-Dimethylbutadiene
Isoprene
Cyclopentadiene
f
f
e
b
e
b
2
e
b
e
b
a
Electronic chemical potential m and chemical hardness h in atomic units; global electrophilicities v in eV as defined by Eqn 1; DNmax
in electron units.
b
Reference 43.
Reference 44.
This work.
Reference 43.
c
d
e
f
Reference 67.
transition state, TS1, to form the [4þ2] cycloadduct 13; (3) the
conversion of 13 into the [2þ4] adduct 12 through a transition
state TS2 corresponding to a [3,3] sigmatropic shift. The different
stationary points of the interaction are shown, together with the
atom numbering, in Scheme 3 and Fig. 3. The energetic results are
collected in Table 2 while the geometries of the transition states
are given in Fig. 4.
B3LYP/6-31G* calculations allow the characterization of the
pre-reaction complex, PRC1, whose formation is associated with a
stabilization energy of 3.0 kcal/mol. Additional calculations using
[
75,76]
the basis set superposition error (BSSE) method
confirm that
the formation of PRC1 corresponds to a real minimum on the
potential energy surface, predicting however a lower stability
k
Figure 1. Local electrophilicity indices v for NBDF (in eV)
(
6
1.3 kcal/mol) for this species. Also, calculations at the B3LYP/
-311þþG* level predict the formation of PRC1 with a
stabilization energy of 1.7 kcal/mol. The reaction of PRC1 has
reactivity patterns experimentally observed for DNBF and ANBF
cycloadditions, as depicted in Schemes 1 and 2, are fully
consistent with the C7 carbon being the most electrophilic center
[
54,55]
also been studied through NBO analysis.
This shows that the
molecular complex is of the CT type, arising from the interaction
between the bonding p-molecular orbital of Cp with the
antibonding s*-molecular orbital of the NBDF molecule.
[
26,37]
of the parent molecules.
unsubstituted C5 carbon of NBDF is by far associated with the
greatest local electrophilicity (v
Figure 1 shows that the
k
¼ 1.08), implying that this
Surprisingly, previous calculations carried out at the same level
of theory did not lead to the characterization of similar
prereaction complexes in the DNBF/Cp and ANBF/Cp inter-
position should be the preferred site for a nucleophilic addition
process. As shown below, this reactivity is also in agreement with
the asynchronicity found to prevail in the TS for formation of the
[
43,44]
actions.
Nevertheless, relatively stable CT-complexes have
[
4þ2] cycloadduct 13.
been experimentally characterized in the reactions of DNBF and
NBDF with donor molecules such as naphthalene.
[
77]
Exploration of the MERP for the NBDF/Cp interaction allows
the characterization of the transition state TS1 associated to the
attack of Cp on the nitroolefinic fragment of NBDF within the
prereaction complex. The activation barrier for this process which
leads to the [4þ2] cycloadduct 13 is 15.3 kcal/mol. As shown in
Fig. 4, TS1 is a highly imbalanced transition state with the
MERP for the NBDF/Cp interaction
A thorough analysis of the gas-phase results reveals that the
Diels–Alder reaction of NBDF with Cp to give the thermo-
dynamically stable and isolable [2þ4] adduct 12 consists of three
steps: (1) the initial formation of a molecular complex of the
charge transfer type type named PRC1, whose geometry is given
in Fig. 2; (2) movement through the highly asynchronous
˚
formation of the C5—C10 bond (1.931 A) being strongly ahead of
˚
the formation of the O4—C11 bond (2.540 A). This situation
J. Phys. Org. Chem. 2009, 22 298–307
Copyright ß 2008 John Wiley & Sons, Ltd.
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D. V. STEGLENKO ET AL.
˚
Figure 2. Main bond lengths (in A) for pre-reaction complexes PRC1 and PRC2 identified in the reaction of NBDF with Cp in the gas phase and in
dichloromethane (in square brackets)
reflects the large polar character of the cycloaddition affording
the adduct 13 in which Cp is acting essentially as a nucleophile.
It follows that TS1 is strongly zwitterionic in nature, even
though the calculations did not provide evidence for the
zwitterion 14 being an intermediate along the reaction
coordinate of the interaction. A consequence of the zwitterionic
character of TS1 is that the O4—C11 distance is markedly shorter
In agreement with the experimental evidence that the [2þ4]
cycloadduct 12 is the thermodynamically stable product of
the NBDF/Cp interaction, the calculations have allowed the
characterization of a transition state, TS2 corresponding to
the conversion of 13 into 12 via a [3,3] sigmatropic shift.
The activation barrier for this process in the gas phase is high
(27 kcal/mol), perhaps due to B3LYP overestimation of the energy
of the intermediate 13, but the energy level of TS2 (11.1 kcal/mol)
is lower than that of TS1 (12.3 kcal/mol). It should be mentioned
that the energy barrier of transformation 12 ! 13 estimated by
˚
than the distance between the C4 and C13 atoms (3.168 A), due to
a favorable coulombic interaction between the two former
atoms. Importantly, this interaction accounts for the preferred
formation of the IED adduct 13 rather than the related NED
adduct 12. It also explains the large endo selectivity observed in
the NMR method is 26.4 kcal/mol, i.e. it is very close to the B3LYP
result. The calculations at the B3LYP/6-31G* do not properly
[
44]
this polar cycloaddition.
account for the relative stabilities of the two adducts, however,
Figure 3. Energy profile for the NBDF/Cp interaction. The solid lines correspond to gas phase processes while the dotted lines correspond to reactions in
dichloromethane.
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Copyright ß 2008 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2009, 22 298–307

POLAR DIELS–ALDER CYCLOADDITION
a
Table 2. Total (E, in a.u.) and relative (DE, in kcal/mol) energies of the stationary points of the Diels–Alder reaction between
-nitrobenzodifuroxan (NBDF, 11) and cylopentadiene (Cp), in the gas phase and in dichloromethane, as derived from B3LYP/6-31G*
4
calculations
Gas phase
Dichloromethane
b
DE
c
E
E
DE
DE
Cp
ꢀ194.10106
ꢀ953.91950
ꢀ1148.02535
ꢀ1148.00102
ꢀ1148.04582
ꢀ1148.00292
ꢀ1148.04384
ꢀ1148.02554
ꢀ1147.99648
ꢀ1148.04461
—
—
—
—
ꢀ194.10230
ꢀ953.92753
ꢀ1148.03263
ꢀ1148.01532
ꢀ1148.05800
ꢀ1148.01882
ꢀ1148.05238
ꢀ1148.03285
ꢀ1148.01005
ꢀ1148.05351
—
—
NBDF
PRC1
TS1
13
TS2
ꢀ3.0
ꢀ2.6
ꢀ1.8
12.3
ꢀ15.9
11.1
13.8
ꢀ11.6
13.6
9.1
ꢀ17.7
6.9
1
2
ꢀ14.6
ꢀ3.1
15.1
ꢀ15.1
ꢀ10.3
ꢀ2.6
16.7
ꢀ10.7
ꢀ14.1
ꢀ1.9
12.4
ꢀ14.9
PRC2
TS3
1
5
a
Relative to the total energy of isolated reagents NBDF and Cp.
Relative energies including the zero point energy (ZPE) correction.
The SCF energy after PCM corrections.
b
c
˚
Figure 4. Main bond lengths (in A) in the transition states pertaining to the various steps involved in the NBDF/Cp interaction (Scheme 3) in the gas
S1
phase and in dichloromethane solution (in square brackets). The unique imaginary frequencies (in cm ) are also given
J. Phys. Org. Chem. 2009, 22 298–307
Copyright ß 2008 John Wiley & Sons, Ltd.
www.interscience.wiley.com/journal/poc

D. V. STEGLENKO ET AL.
Two other results are noteworthy: (1) there is a rather similar
˚
development in the breaking of the O4—C11 bond (2.491 A) and
˚
the formation of the C4—C13 bond (2.661 A) at TS2 for the
Table 3. Total (E, in a.u.) and relative energies (DE, in kcal/mol)
of the stationary points of the Diels–Alder reaction between
NBDF 11 and Cp in the gas phase, as derived from ab initio
sigmatropic shift leading from 13 to 12; (2) a X-ray structure of
[45,46]
(
HF/6-31G*) calculations
1
selectivity of the cycloaddition. Figure 5 shows the remarkable
2 has been made,
leaving no doubt regarding the endo
a
b
E
DE
DE
agreement between the X-ray data and the geometrical
characterization of 12, as deduced from B3LYP/6-31G* calcu-
Cp
ꢀ192.79172
ꢀ948.66478
ꢀ1141.46103
ꢀ1141.41630
ꢀ1141.48247
ꢀ1141.42423
ꢀ1141.49060
ꢀ1141.46131
ꢀ1141.40927
ꢀ1141.49241
—
—
—
—
lations. To confirm that the endo approach is by far the preferred
mode of reactivity in the NBDF/Cp interaction, calculations have
been extended to the exo approach of Cp relative to the NO2
substituent of NBDF. As shown in the left part of Fig. 3, a
prereaction complex (PRC2) of the same stability as the one
involved in the endo mode of reactivity is initially found. Then,
only one transition state of imbalance character (TS3) corre-
sponding to a direct formation of the exo [2þ4] adduct 15 could
be identified. Interestingly, the activation barrier for this polar
cycloaddition is 2.9 kcal/mol higher than the one for the
formation of the endo [4þ2] adduct 13. At the same time, the
energy level of TS3 is 2.8 kcal/mol higher than that of TS1, in full
agreement with the non-observation of 15.
NBDF
PRC1
TS1
13
TS2
ꢀ2.8
ꢀ2.4
25.2
ꢀ16.3
20.2
26.6
ꢀ11.3
23.0
1
2
ꢀ21.4
ꢀ3.0
29.6
ꢀ22.5
ꢀ16.3
ꢀ2.6
31.0
ꢀ17.5
PRC2
TS3
1
5
a
Relative to the sum total energy of isolated reagents.
Relative energies including the zero point energy (ZPE)
b
correction.
since they predict that the [4þ2] adduct 13 is 1.3 kcal/mol more
stable than the [2þ4] adduct 12. In the current DFT approach, it is
not possible to estimate the error of the calculations without
comparing them to other methods or experiments. We have
recalculated for the gas phase all stationary points mentioned
above by the HF/6-31G* method (Table 3). Going to the HF/
6
-31G* level reveals that 12 is in fact more stable than 13 by
The extent of the charge transfer occurring along the polar
5
.1 kcal/mol, in full consistency with experimental obser-
NBDF/Cp reactions has been evaluated through
analysis.
a
NBO
The transfer of negative charge from Cp, the donor
molecule, to NBDF, the acceptor molecule is 0.38e at TS1 and 0.35e
[
44]
[54,55]
vations.
At the same time the relative stabilities of all other
structures are qualitatively analogous to DFT results in Table 2.
Figure 5. The geometrical characteristics of the [2þ4] cycloadduct 12 according to B3LYP/6-31G* calculations (a) and X-ray analysis (b). Bond lengths
˚
are given in A and bond angles in degrees.
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J. Phys. Org. Chem. 2009, 22 298–307

POLAR DIELS–ALDER CYCLOADDITION
at TS3. This clearly supports the zwitterionic character of the
transition states. Also of interest are the results of an analysis of the
atomic motion at the unique imaginary frequency of TS1
characterized by NMR under appropriate experimental con-
ditions.
As a matter of fact, treatment of NBDF by Cp at ꢀ10 8C in
ꢀ
1
ꢀ1
1
(343cm ) and TS3 (394cm ). This analysis reveals that these
acetone resulted in complex H NMR spectra (Figure S1)
two transition states are for the most part associated to the
movement of the C5 and C10 atoms along the developing C5—C10
bond. The movement of other important atom sites, i.e. O4, C11, C4,
and C13, is insignificant. It thus appears that the related
cycloadditions proceed as simple two-center interactions. Regard-
ing TS2, the analysis at the unique imaginary frequency of
consistent however, with the formation of a mixture of two
products. Notably, one of these products was identical to the
previously characterized NED adduct 12 in a pure form. This, as
well as the progressive clarification of the spectra observed upon
raising the temperature at 20 8C and shifting the interaction
towards the complete formation of 12, aids in the recognition of
the various resonances assignable to the adduct 13 (Figures
S1–S4). The H NMR data for this species are given in Table 4
together with similar data previously collected for the related IED
adducts of ANBF and DNBF.
ꢀ
1
160 cm confirms that the breaking of the O4—C11 bond and the
1
formation of the C4—C13 bond are essentially coupled (vide supra).
Going to dichloromethane solution does not cause significant
changes in the gas phase geometries (Figs 3 and 4) while
increasing markedly the stabilization of the polar transition
states (Table 2). This results in lower activation barriers for
the cycloadditions in CH Cl with, however, no modification in
the reactivity pattern found in the gas phase. In particular, all
attempts to locate a zwitterionic intermediate and a second
transition state associated to a stepwise mechanism for formation
of 13 have failed.
As diagnostic features for structure 13 there is the presence of
a doublet at d ¼ 4.72 ppm assignable to the proton H5 and a
multicoupled signal at d ¼ 4.15 ppm typical of the proton H10.
Also supporting structure 13 is the close similarity of the chemical
shifts pertaining to this adduct and the related DNBF and ANBF
adducts 6, 7, and 9, respectively. While it is noteworthy that the
IED Diels–Alder reaction leading to 13 proceeds diastereoselec-
tively, as it does for 6, 7, and 9, it should be noted that Nuclear
Overhauser Effects (NOE) experiments did not allow a firm
discrimination between the two diastereomeric structures 13 and
2
2
Characterization of the transient [4R2] cycloadduct 13
1
6 through NOE experiments. However, the close analogy
3
3
A most significant feature which emerges from the above
calculations is that the NBDF/Cp interaction proceeds via the
initial formation of the IED adduct 13 in a strongly exothermic
process, i.e. DE ¼ ꢀ15.9 kcal/mol in the gas phase. Then the
conversion of 13 into the thermodynamically more stable adduct
between the J
and the related J
coupling constant in 13 ( J
¼ 5.4 Hz)
H5H10
3
H5H10
coupling constant in the DNBF adducts 6
H7H10
3
and 7 ( JH7H10 ¼ 5.9 Hz) strongly supports the view that the
[
37]
stereochemistry firmly established for 6 and 7 (X-ray structure)
also holds for 13. As a matter of fact, gas phase calculations show
that 16 is both kinetically (DE ¼ 4.1 kcal/mol) and thermodyna-
mically (DE ¼ 1 kcal/mol) less favored than 13.
1
2 occurs with a large activation barrier of 27 kcal/mol. These
figures suggested that 13 should have a sufficient lifetime to be
1
a
Table 4. H NMR data for the cyclopentadiene [4þ2] adducts of DNBF (6), ANBF (9), and NBDF (13)
b
c
3
b 3
JH7H10 JH5H10
c
Compound
H5
H7 H5
H10
H11
H12
H13
H14
6
7
9
1
(CDCl3)
8.33
—
8.66
—
4.32
4.06
4.26
4.72
4.13
3.98
4.01
4.15
5.89
5.77
5.92
5.76
5.92
5.95
5.92
5.93
6.24
6.21
6.17
6.08
2.59/1.96
2.41/2.16
2.57/1.97
2.50/2.32
5.9
5.9
5.6
5.2
(CDCl
(CDCl
3
)
)
3
6
3 (Acetone-d )
a
b
c
d in ppm and J in Hertz.
H7 for structures 6, 7, and 8.
H for structure 13.
5
J. Phys. Org. Chem. 2009, 22 298–307
Copyright ß 2008 John Wiley & Sons, Ltd.
www.interscience.wiley.com/journal/poc

D. V. STEGLENKO ET AL.
CONCLUSION
[12] M. J. Strauss, R. A. Renfrow, E. Buncel, J. Am. Chem. Soc. 1983, 105,
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[
[
13] E. Buncel, R. A. Renfrow, M. J. Strauss, J. Org. Chem. 1987, 52, 488–495.
14] R. A. Manderville, E. Buncel, J. Chem. Soc. Perkin Trans. 2 1993, 1887–
Combining the information provided by DFT calculations and
experimental studies has allowed to delineate the mechanism of
the Diels–Alder interaction of NBDF with Cp to afford the [2þ4]
adduct 12 as the thermodynamically stable product and
synthetically isolable compound. Contrasting with the results
for the DNBF/Cp interaction (Scheme 1), no zwitterionic
intermediate of sufficient stability could be identified on the
reaction coordinate leading to the two characterized cycload-
ducts 12 and 13 (Scheme 3). Instead, it is found that the reactivity
pattern of the NBDF/Cp system is similar to the one established
for the ANBF/Cp system (Scheme 2), with the initial formation of
the [4þ2] adduct 13 being followed by its conversion into 12 via
a [3þ3] sigmatropic shift. Interestingly, the observed mechanistic
differences are consistent with the positioning of the three
electrophiles on the global electrophilicity scale, v, introduced by
Parr et al. With v values of 4.81 and 4.80, respectively, ANBF and
NBDF react similarly with Cp, exhibiting a strong electrophilicity
which is not, however, sufficient to generate a zwitterionic
intermediate, i.e. 10 or 14 of definite stability. Going from NBDF to
DNBF strongly increases the electrophilicity, as measured by a
jump of v to 5.46. The inference of the superelec-trophilicity of
DNBF is that the putative zwitterionic intermediate 4 arising from
the nucleophilic addition of Cp is now stable enough to exist as a
discrete entity along the reaction coordinate.
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6
[
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Nitrobenzodifuroxan 11 was synthesized according to
a
7
7
procedure reported by A. S. Bailey and J. R. Case. : mp
7
8
1
58–159 8C (lit. 158 8C). Cp was obtained from the heating of
bicyclopentadiene and was used without further purification.
1
13
H and
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C NMR spectra were recorded on a 300 MHz
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