Indian Journal of Chemistry
Vol. 53A, Aug-Sept 2014, pp. 940-948
High reactivity of triazolinediones as superelectrophiles in
polar reactions: A DFT study
Luis R Domingoa, * & Saeed R Emamianb
a
Departamento de Química Orgánica, Universidad de Valencia, Dr Moliner 50, E-46100 Burjassot, Valencia, Spain
Email: [email protected]
b
Chemistry Department, Shahrood Branch, Islamic Azad University, Shahrood, Iran
Received 28 March 2014; revised and accepted 14 April 2014
The mechanism of the polar reaction between the superelectrophile PTAD (2) and diene (6b) in the presence of THF has
theoretically been studied at the MPWB1K/6-311G** level. Our investigations reveal that this reaction takes place through a
stepwise mechanism via formation of intermediate (7b) with a strong zwitterionic character. The first step of the reaction, which
is associated with the nucleophilic attack of diene (6b) on PTAD (2), presents complete endo selectivity. Formation of the
expected formal [4+2] cycloadduct (8b) quickly takes place through a ring closure process which is much favoured both
energetically and geometrically. However, formation of (8b) is a reversible process. Interestingly, intermediate (7b) undergoes a
1,7-hydrogen shift process yielding the major ene adduct (9b), which is thermodynamically very stable. Analysis of relative
Gibb free energies suggests that while the expected formal [4+2] cycloadduct (8b) is obtained under kinetic control, the
experimentally observed ene adduct (9b) is formed under thermodynamic control. Finally, analysis of the DFT reactivity
indices of the reagents accounts for the high reactivity of PTAD (2) acting as a superelectrophile, and the asynchronicity found
in the C-N single bond formation as a consequence of the asymmetric nucleophilic activation of diene system of (6b).
Keywords: Theoretical chemistry, Chemical reactivity, Superelectrophiles, Density functional calculations, Triazolinediones
4-Substituted-1,2,4-triazoline-3,5-diones (TADs) are
highly versatile reagents notable for their ability
to participate in a wide range of reactions;
for instance, electrophilic aromatic substitutions1,2,
dehydrogenations3, oxidations4-6, condensations7, and
Diels-Alder (DA) reactions8-12. TADs are among the
most reactive electrophilic dienophiles, yielding DA
cycloadducts under mild reaction conditions.
4-Arylsubstituted TADs (PTAD) are the most
commonly employed TADs for DA reactions.
Recently, Fernandez-Herrera et al.13 reported the
rapid DA reaction of the in situ generated TAD (2)
with the steroidal diene (1) yielding cycloadduct (3)
(see Scheme 1). More recently, Merino et al.14
performed a density functional theory (DFT) study
on the reaction mechanism of this polar Diels-Alder
(P-DA) reaction. DFT calculations showed that the
reaction takes place through a one-step mechanism
via a high asynchronous transition state (TS). This
P-DA reaction was found to be completely endo
and β-facial selective. Analysis of DFT reactivity
indices explained the high reactivity of TADs as a
consequence of their superelectrophilic character,
which is enhanced with the presence of an electronwithdrawing nitro group on the para position of the
aromatic ring of PTAD (2).
The reaction of a 4-alkenylthiazole (4) with PTAD
(2)15 was reported to afford a polyheterocyclic
compound (5) through a DA reaction (see Scheme 2)16.
Considering the structural similarity between thiazole
(4) and 1,2,3-triazole (6), Zhu et al.17 assumed that
4-alkenyl-1,2,3-triazoles such as (6) may also undergo
DA reactions with dienophiles, resulting in fused
heterocycles with a 100% atom economy.
DOMINGO & EMAMIAN: DFT STUDIES ON REACTIVITY OF TRIAZOLINEDIONES IN DIPOLAR REACTIONS
However, when alkenyl-1,2,3-triazole (6a) was
treated with PTAD (2), the two ene adducts (9a)
and (10a) were obtained at room temperature
in a few minutes instead of the expected [4+2]
cycloadduct (8a) (Scheme 3).
Considering the fact that in the presence of water,
as a result of the addition of the water molecule to
the feasible zwitterionic intermediates, secondary
products were also obtained, Zhu et al.17 proposed
the stepwise mechanism, given in Scheme 3, for
the formation of ene adducts (9a) and (10a).
The electrophilic addition of PTAD (2) to diene (6a)
could involve a zwitterionic intermediate18-22 (7a).
This zwitterionic intermediate containing a benzyliclike cation could undergo a hydrogen shift to afford
enamide (10) and major product (9) (see Scheme 3)23.
In addition to these competitive pathways, the
zwitterionic intermediate (7a) could also experience
a ring closure yielding the formal [4+2] CA (8a),
which in turn could tautomerise into the main ene
reaction product (9).
Due to these unexpected experimental results, we
decided to carry out a DFT study on the mechanism
of the reaction between PTAD (2) and diene (6b),
in which the benzyl substituent present in (6a)
was substituted by a methyl group, at the
MPWB1K/6-311G** level. Our aim is to explain
why the ene adduct (9a) was experimentally obtained
instead of the expected [4+2] CA (8a).
Computational Methods
DFT computations were carried out using the
MPWB1K24 functional, together with the standard
941
6-311G** basis set25. Optimisations were carried out
using the Berny analytical gradient optimisation
method26,27. The stationary points were characterised
by frequency computations in order to verify that
TSs have one and only one imaginary frequency.
The IRC paths28 were traced in order to check the
energy profiles connecting each TS to the two
associated minima of the proposed mechanism using
the second order González-Schlegel integration
method29,30. Solvent effects of tetrahydrofuran (THF)
were taken into account through geometrical
optimisations using the polarisable continuum model
(PCM) as developed by Tomasi’s group31,32 in
the framework of the self-consistent reaction field
(SCRF)33,35. Values of enthalpies, entropies and
free energies in THF were calculated with the
standard statistical thermodynamics25 at 25.0 ºC and
1 atm. The electronic structures of stationary points
were analysed by the natural bond orbital (NBO)
method36,37. All computations were carried out with
the Gaussian 09 suite of programs38.
The global electrophilicity index39, ω, is given by
the following expression, ω = (µ2/2η), in terms
of the electronic chemical potential, µ, and the
chemical hardness, η. Both quantities can easily be
approximated in terms of the one-electron energies
of the frontier molecular orbital HOMO and LUMO,
εH and εL, as µ ≈ (ε H + ε L ) / 2 and η ≈ (ε L − ε H ) ,
respectively40,41. Recently, we introduced an empirical
(relative) nucleophilicity index42 (Ν) based on the
HOMO energies obtained within the Kohn-Sham
scheme43, and defined as Ν = εHOMO(Nu) - εHOMO(TCE).
942
INDIAN J CHEM, SEC A, AUG-SEPT 2014
Nucleophilicity is referred to tetracyanoethylene
(TCE), because it presents the lowest HOMO energy
in a large series of molecules already investigated in
the context of polar cycloadditions. This choice
allows us to handle conveniently a nucleophilicity
scale of positive values. Electrophilic Pk+ and Pk−
nucleophilic Parr functions44, were obtained through
the analysis of the Mulliken atomic spin density
(ASD) of the radical anion and the radical cation by
single-point energy calculations on the optimised
neutral geometries.
Results and Discussion
The reaction mechanism of PTAD (2) with triazole
diene (6b) leading to the formal [4+2] cycloadduct
(8b) and/or the ene adducts (9b) and (10b) was
studied at the MPWB1K/6-311G** level in the
presence of THF as solvent. Analysis of the stationary
points located on the potential energy surfaces (PES)
indicates that the reaction under investigation takes
place through a stepwise mechanism with formation
of a zwitterionic intermediate. From this intermediate,
the reactive channels associated with the formation of
formal [4+2] cycloadduct (8b) or the ene adducts (9b)
and (10b) were located and characterized. In addition,
for the first step of this stepwise mechanism, two
stereoisomeric channels leading to the conformational
zwitterionic intermediates (7b) and (7b'), are feasible,
the endo and the exo. Consequently, the reagents (2)
and (6b), two stereoisomeric TSs associated with
the nucleophilic attack of (6b) on (2), i.e., (TS1n)
and (TS1x), two zwitterionic intermediates (7b) and
(7b') and the TS associated with the ring closure in
(7b), i.e., (TS2) and those associated with formation
of the ene adducts (9b) and (10b), i.e., (TS3) and
(TS4), were located and characterized (see Scheme 4).
The corresponding thermodynamic data in the
presence of THF are given in Table 1.
The IRC from (TS1n) and (TS1x) to reactants (2)
plus (6b), stops in the molecular complex (MC)
in which the two reagents present a parallel
rearrangement with a separation ca 3.0 Å. (MC),
which is enthalpically 8.1 kcal/mol more stable than
the separate reactants, is formed by the incipient
global charge transfer (GCT) that takes place in an
earlier stage of the reaction. However, formation of
(MC) is endergonic by 6.2 kcal/mol due to the
negative entropic term (-48.0 cal/mol K) associated
with bringing two molecules together. Thus, (MC)
does not have any significant impact on the Gibb free
energy profile.
The activation enthalpies associated with the
nucleophilic attacks of the C1 carbon of diene (6b)
on the N6 nitrogen of PTAD (2) along the
two stereoisomeric channels are 2.1 (TS1n) and
16.5 (TS1x) kcal/mol. The activation enthalpy along
the most favourable endo reactive channel is very
low, which is in clear agreement with the
superelectrophilic character of PTAD (2) and the
strong nucleophilic character of the diene (6b)
DOMINGO & EMAMIAN: DFT STUDIES ON REACTIVITY OF TRIAZOLINEDIONES IN DIPOLAR REACTIONS
943
Table 1 – MPWB1K/6-311G** total and relativea energies (E and ∆E), enthalpies (H and ∆H), entropies (S and ∆S), Gibbs free
energies (G and ∆G), computed at 25.0 °C and 1.0 atm in the presence of THF, for the stationary points involved in the reaction
between (2) and (6b)
Species
6b
2
MC
TS1n
TS1x
7b
7b'
TS2
TS3
TS4
8b
9b
10b
E
(a.u.)
-514.859484
-622.395541
-1137.270532
-1137.253399
-1137.229433
-1137.270890
-1137.267012
-1137.268525
-1137.264422
-1137.228685
-1137.293174
-1137.324682
-1137.326040
∆E
(kcal/mol)
Hb
(a.u.)
-9.7
1.0
16.1
-10.0
-7.5
-8.5
-5.9
16.5
-23.9
-43.7
-44.6
-514.6368
-622.2607
-1136.91046
-1136.89416
-1136.87119
-1136.90977
-1136.90642
-1136.90815
-1136.90762
-1136.87319
-1136.93086
-1136.96189
-1136.96399
∆H
(kcal/mol)
Sb
(cal/mol K)
-8.1
2.1
16.5
-7.7
-5.6
-6.7
-6.4
15.3
-20.9
-40.4
-41.7
106.1
98.1
156.2
148.9
152.2
148.0
156.1
144.9
151.1
157.3
149.5
153.3
155.2
∆S
(cal/mol K)
Gb
(a.u.)
∆G
(kcal/mol)
-48.0
-55.3
-52.0
-56.3
-48.1
-59.3
-53.1
-46.9
-54.7
-50.9
-49.1
-514.687209
-622.307317
-1136.98469
-1136.9649
-1136.94349
-1136.98007
-1136.98058
-1136.97700
-1136.97942
-1136.94793
-1137.00188
-1137.03471
-1137.03771
6.2
18.6
32.0
9.1
8.8
11.0
9.5
29.2
-4.6
-25.2
-27.1
a
relative to (2+6b).
scaled by 0.96.
b
(see later); the first reaction path being completely
endo selective. When the corresponding activation
entropies are included, the values of 18.6 and
32.0 kcal/mol, as a consequence of the bimolecular
nature of these additions, are obtained for activation
Gibbs free energies for (TS1n) and (TS1x),
respectively. The low activation Gibbs free energy
associated with formation of the first C1-N6 single
bond could be responsible for the experimental
occurrence of the reaction at room temperature.
While the gas phase IRC from the most
unfavourable (TS1x) to the product terminates by
formation of formal [4+2] cycloadduct (8b) through a
two-stage one-step mechanism, corresponding
calculations in THF confirm the presence of a weak
zwitterionic intermediate (7b') as a stationary point.
It is noteworthy that in spite of this apparent change
of mechanism, both two-stage one-step and two-step
mechanisms are non-concerted processes. On the
other hand, while in stepwise P-DA reactions
involving hydrocarbon systems, endo and exo
intermediates are pairs of diastereomers, in this
P-DA reaction involving the heterodienophile (2),
intermediates (7b) and (7b') are one pair of
conformers due to the sp2 hybridisation of the
N5 nitrogen atom. Formation of the zwitterionic
intermediates are endergonic by 9.1 kcal/mol (7b)
and 8.8 (7b') kcal/mol.
The analysis of the geometry of intermediate
(7b) shows that the position of the C4 carbon of
diene framework is very close to the N5 nitrogen
of the PTAD. Consequently, it is expected that the
subsequent ring closure step with formation of the
new C4-N5 single bond will be very favoured so that
the activation enthalpy associated with the ring
closure in (7b) via (TS2), is 1.0 kcal/mol. If the
activation entropy is taken into account, the activation
Gibbs free energy of 1.9 kcal/mol is obtained for
(TS2). Therefore, it is expected that the ring closure
step does not have any kinetic limitation. Formation
of the formal [4+2] cycloadduct (8b) is exothermic by
20.9 and exergonic by only 4.6 kcal/mol.
Interestingly, the activation Gibbs free energy for
the ring cleavage in cycloadduct (8b) to yield
intermediate (7b) via (TS2), is only 15.6 kcal/mol,
i.e., it is lower than that associated with the (TS1n)
for which it is 18.6 kcal/mol. Consequently, the
cyclisation is a reversible process at room temperature.
In addition, (TS2) is located ca. 8 kcal/mol below
(TS1n) on the Gibbs free energy surface. Therefore,
the formal [4+2] cycloadduct (8b) can equilibrate
with intermediate (7b) without the need to form the
initial reagents (2 + 6b).
Finally, formation of the experimentally observed
ene adducts (9b) and (10b) is exergonic by 25.2
and 27.1 kcal/mol, respectively. Therefore, formation
944
INDIAN J CHEM, SEC A, AUG-SEPT 2014
of these products can be considered irreversible.
Thus, while the formal [4+2] cycloadduct (8b) may be
the product of kinetic control, if ene adducts (9b)
and (10b) could be connected to the zwitterionic
intermediate (7b), they might be the products of a
thermodynamic control.
Isomerisation of intermediate (7b), into ene
adducts (9b) and (10b) demands a 1,7- or a
1,3-hydrogen shift, respectively. These processes are
acid/base reactions between the basic N5 nitrogen
and the acidic hydrogens H1 and H7 as a consequence
of the high zwitterionic character of intermediate
(7b) (see later). Due to the free C1-N6 bond rotation
in (7b), the basic N5 nitrogen can approach these
acidic hydrogen atoms, favouring the isomerisation in
only one step. The activation enthalpies associated
with these acid/base reactions are 1.3 kcal/mol (TS3)
and 23.0 kcal/mol (TS4). Inclusion of the activation
entropies leads to the activation Gibbs free energies
of 0.4 kcal/mol (TS3) and 20.1 kcal/mol (TS4).
The activation enthalpy associated with the
intramolecular (TS4) is very high as a consequence of
the strain caused by formation of the four membered
TS45. However, acid/base reactions are fast, thus,
it is expected that the isomerisation in which the
H1 hydrogen atom participate, could take place via
an intermolecular process involving any acid/base
species included in the reaction medium. On the other
hand, the activation enthalpy associated with the
intramolecular (TS3) is very low given that the strain
generated in the four membered (TS4) is avoided
during formation of the six membered (TS3). Note
that ene adduct (9b), which comes from intermediate
(7b) via a 1,7-hydrogen shift, is the main product of
the reaction, while ene adduct (10b) is a secondary
product of the reaction.
The relative Gibbs free energies of stationary points
involved in the polar reaction between PTAD (2)
and triazole diene (6b) are depicted in Fig. 1.
As shown herein, (TS1n) associated with the
nucleophilic attack of diene (6b) on PTAD (2) is only
located 18.6 kcal/mol above the separated reagents.
On the other hand, this TS presents the highest
relative Gibbs free energy on the path of the
least energy. Consequently, intermediate (7b), the
subsequent TSs, and the reaction products (8b), (9b)
and (10b) could be thermodynamically equilibrated.
As mentioned above, (TS2) associated with the ring
closure process is energetically and geometrically
very favourable, i.e., the formal [4+2] cycloadduct
(8b) is being formed through kinetic control.
Considering the fact that formation of (8b) is not very
exergonic (-4.6 kcal/mol), the ring cleavage in this
cycloadduct is not higher in Gibbs free energy than
15.6 kcal/mol. Consequently, (8b) can equilibrate
with intermediate (7b). Interestingly, due to the high
zwitterionic character of intermediate (7b) (see later),
the H1 and H7 hydrogens have a large acidic
character, while the N5 nitrogen has a large basic
character. The easy and unconstrained orientation of
the N5 nitrogen to the H7 hydrogen favours an
intramolecular acid/base reaction leading to formation
of ene adduct (9b) via an intramolecular 1,7 hydrogen
shift. Due to the exergonic character of the formation
Fig. 1 – Gibbs free energy profile associated with the polar reaction between triazole diene (6b) and PTAD (2).
DOMINGO & EMAMIAN: DFT STUDIES ON REACTIVITY OF TRIAZOLINEDIONES IN DIPOLAR REACTIONS
of (9b), (25.2 kcal/mol), this acid/base process
comes irreversible and thus, the main product of the
reaction (9b) is being formed under thermodynamic
control.
The optimised geometries of TSs and intermediates
involved in the polar reaction between triazole
diene (6b) and PTAD (2) in the presence of THF
are depicted in Fig. 2. At the stereoisomeric
TSs associated with the nucleophilic attack of the
C1 carbon of diene (6b) on the N6 nitrogen of PTAD
(2), the C1-N6 distances are 1.896 Å (TS1n) and
1.867 Å (TS1x), while the distances between the
C4 and N5 centers are 2.573 Å (TS1n) and 2.594 Å
(TS1x). At intermediates (7b) and (7b'), the length of
the C1-N6 single bond is 1.471 Å and 1.423 Å, while
the distances between the C4 and N5 centers are
2.461 Å and 2.860 Å, respectively. The length of the
C1-N6 single bond at these intermediates indicates
that the C1-N6 single bond is practically formed.
At (TS2) associated with the ring closure in
intermediate (7b), the distance between the C4 and
945
N5 centers is 2.007 Å, while the distance between the
C1 and N6 centers is 1.472 Å. At the TSs associated
with the 1,7- or the 1,3-hydrogen shift the lengths of
the C-H7 and C-H1 breaking bonds are 1.234 Å
(TS3) and 1.308 Å (TS4), while the lengths of the
N5-H7 and N5-H1 forming bonds are 1.534 Å (TS3)
and 1.529 Å (TS4).
The polar nature of the reaction was analysed by
computing the GCT along the first step of the reaction.
The natural atomic charges, obtained through a natural
population analysis (NPA), shared between the triazole
diene and PTAD frameworks at the TSs and
intermediates reveal that the GCT from the diene moiety
to the PTAD moiety along this P-DA reaction is 0.46 e
at (TS1n), 0.53 e at (TS1x), 0.64 e at (7b), and 0.60 e
at (TS2). These values confirm the high polar character
of this reaction. NPA analysis at (7b) and (7b') indicates
the high zwitterionic character of this intermediate.
At (TS2), the value of the GCT, i.e., 0.60e, decreases
as a consequence of the retro-donation along the ring
closure process.
Fig. 2 – MPWB1K/6-311G** optimised geometries including some selected bond distances (in Å) for TSs and intermediates involved in
the investigated polar reaction in the presence of THF.
946
INDIAN J CHEM, SEC A, AUG-SEPT 2014
Analysis of the reactivity indices
Recent studies carried out in organic reactions have
shown that the reactivity indices defined within the
conceptual DFT are powerful tools for establishing
their polar character. In Table 2 the global properties,
namely the electronic chemical potential (µ), chemical
hardness (η), global electrophilicity (ω) and global
nucleophilicity (N), all in eV, for PTAD (2) and diene
(6b) are summarized.
The electronic chemical potential µ of diene (6b),
-2.99 eV, is higher than that of PTAD (2), -5.50 eV,
indicating that the GCT along the corresponding
polar reaction will take place from the diene toward
the electron-deficient PTAD, in complete agreement
with the flux of the electron density computed at
(TS1n) and (TS1x).
The electrophilicity ω index of PTAD (2) is
4.73 eV, allowing us to classify this reagent as a
strong electrophile on the electrophilicity scale46.
On the other hand, PTAD (2) has a nucleophilicity
N index of 2.02 eV, thus being classified as a
marginal nucleophile47. The high electrophilicity
of PTAD (2) makes it possible for this neutral
species to be classified as a superelectrophile14.
Note that the electrophilicity of PTAD (2) is similar
to that of heteroaromatic 4-aza-6-nitrobenzofuroxan48
(ω = 4.81 eV), which has been experimentally
classified as a superelectrophile49.
As expected, diene (6b) shows a low
electrophilicity ω index (0.81 eV), thus being
classified as a moderate electrophile. On the
other hand, it presents a nucleophilicity N index of
3.37 eV, being classified as a strong nucleophile.
Consequently, the very high electrophilicity ω index
displayed by PTAD (2) together with the high
nucleophilicity N index displayed by diene (6b)
suggests that this reaction will have a high polar
character, and a very low activation energy, in
agreement with the low computed activation energy.
Recently, Domingo & co-workers44 have
established that the asynchronicity in the C–C bond
formation in polar reactions is controlled by the
asymmetric distribution of the excess of electrondensity reached in the electrophile and/or the
shortage of electron-density reached in the
nucleophile through the GCT process, which can be
anticipated by an analysis of the electrophilic Pk+ Parr
functions in the electrophiles and the nucleophilic Pk−
Parr functions at the nucleophile44. Consequently,
Table 2 – B3LYP/6-31G* electronic chemical potential (µ),
chemical hardness (η), global electrophilicity (ω) and global
nucleophilicity (N), for PTAD (2) and diene (6b)
Species
µ (eV)
η (eV)
ω (eV)
N (eV)
2
-5.50
3.20
4.73
2.02
6b
-2.99
5.51
0.81
3.37
Fig. 3 – Maps of the atomic spin densities of the radical anion (2• –)
+
and of the radical cation (6b• ), and corresponding electrophilic
+
Pk Parr functions for PTAD (2) and nucleophilic Pk− Parr
functions for diene (6b).
the electrophilic Pk+ Parr functions of PTAD (2) and
the nucleophilic Pk− Parr functions of diene (6b) were
computed. The maps of the atomic spin densities of
the radical anion (2• –) and of the radical cation (6b• +),
and corresponding electrophilic Pk+ Parr functions for
PTAD (2) and nucleophilic Pk− Parr functions for
diene (6b) are displayed in Fig. 3.
At the symmetric PTAD (2), as expected, the
electrophilic Pk+ Parr functions are concentrated at
the N5 and N6 atoms ( Pk+ = 0.27). Note that they
represent more than 50% of the total electrophilic Parr
functions of PTAD (2). On the other hand, diene (6b)
shows an asymmetric distribution of the nucleophilic
Pk− Parr functions at the two terminal carbons of
the diene system; Pk− = 0.48 (C1) and 0.19 (C4).
Consequently, the most favourable nucleophilic/
electrophilic interaction along the C-N bond
formation will take place between the C1 carbon
of diene (6b) and one of the two equivalent N5 or
N6 nitrogen atoms of PTAD (2).
DOMINGO & EMAMIAN: DFT STUDIES ON REACTIVITY OF TRIAZOLINEDIONES IN DIPOLAR REACTIONS
Conclusions
The mechanism of the polar reaction between
the superelectrophile PTAD (2) and diene (6b) in
the presence of THF, experimentally reported by
Zhu et al.17 has theoretically been studied at the
MPWB1K/6-311G** level. Based on the calculations
carried out in this work, the reaction under
investigation takes place through a stepwise
mechanism via formation of an intermediate (7b) with
a strong zwitterionic character. The first step of the
reaction, which is associated with the nucleophilic
attack of diene (6b) on one of the two nitrogen atoms
of PTAD (2), presents a complete endo selectivity,
but the endo and exo zwitterionic intermediates (7b)
and (7b') form a pair of conformers as a consequence
of the sp2 hybridization of the nitrogen atom involved
in the C-N single bond formation. Formation of the
expected formal [4+2] cycloadduct (8b) quickly takes
place through a ring closure process, which is much
favoured both energetically and geometrically.
However, formation of (8b) is not much exergonic,
the ring opening yielding intermediate (7b) being
a reversible process.
Interestingly, intermediate (7b) can undergo a
1,7-hydrogen shift process via a quick acid/base
reaction yielding the main ene adduct (9b), which is
thermodynamically very stable. Consequently, while
the expected formal [4+2] cycloadduct (8b) may
be obtained under kinetic control, the experimentally
observed ene adduct (9b) is formed under
thermodynamic control. The low activation Gibbs
free energy associated with formation of the first
C-N single bond through the nucleophilic attack
of diene (6b) on one of the nitrogen atoms of
PTAD (2) below 20 kcal/mol, accounts for the
experimentally occurrence of the reaction at room
temperature.
Analysis of the DFT reactivity indices of the
reagents indicates that both the superelectrophilic
character of PTAD (2) and the strong nucleophilic
character of diene (6b) are responsible for the high
polar character of the reaction. Finally, analysis of
the Parr functions of the reagents indicates that
while PTAD (2) presents a symmetric electrophilic
activation at the two nitrogen atoms, diene (6b) shows
a unsymmetric nucleophilic activation at the carbon
atoms of the diene system. The high nucleophilic
activation of the C1 carbon accounts for the high
asynchronicity found at the TSs associated with the
nucleophilic attack of diene (6b) on PTAD (2).
947
Acknowledgement
This work has been supported by the University of
Valencia, Spain (project UV-INV-AE13-139082).
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