Origin of reversal of stereoselectivity for [4+2] cycloaddition reaction between cyclopentadiene and methyl methacrylate in the presence of the chloroloaluminate ionic liquid (1-ethyl-3-methyl-imidazolium chloride): In silico studies

Article abstract of DOI:10.1139/cjc-2014-0189

The origin of stereoselectivity for [4+2] cycloaddition reaction of methyl methacrylate with cyclopentadiene was investigated with the B3LYP-D3(BJ)/6- 31+G(d)//B3LYP/6-31+G(d) level of theory in the presence of the ionic liquid 1-ethyl-3-methyl-imidazolium chloride (EMI⁺Cl^-) and its acidic chloroaluminate melt, 1-ethyl-3-methyl-imidazolium heptachlorodialuminate (EMI⁺Al₂Cl₇^-). The reaction of methyl methacrylate with cyclopentadiene was examined in the gas phase to rationalize the effect of the ionic liquid ion pairs EMI⁺Cl ^- and EMI⁺Al₂Cl₇^-. The DFT calculated results were found to be in good agreement with the experimentally observed results. The much-discussed hydrogen bonding effect of the imidazolium cation with the dienophile is less important to govern the stereoselectivity for the cycloaddition reaction. The atoms in molecules theory was used to examine the role of hydrogen bonding between the EMI⁺ cation and methyl methacrylate in the transition state geometries. The calculated activation barriers with the M062X/6-31+G(d)//B3LYP/6-31+G(d) and MP2/6-311+G(d,p)//B3LYP/6-31+G(d) levels of theory also predict the similar exo/endo-stereoselectivity trend for the cycloaddition reactions.

Full text of DOI:10.1139/cjc-2014-0189

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Origin of reversal of stereoselectivity for [4+2] cycloaddition reaction
between cyclopentadiene and methyl methacrylate in presence of the
chloroloaluminate ionic liquid (1ꢀEthylꢀ3ꢀmethylimidazoliumchloride): in
silico studies
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DebashisSahu,a,b Manoj K. Kesharwani,a and BishwajitGanguly*a,b
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aComputation and Simulation Unit, Analytical Discipline and Centralized Instrument Facility and
bAcademy of Scientific and Innovative Research; CSIRꢀCentral Salt and Marine Chemicals Research
Institute, Bhavnagar, Gujarat, 364002.
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* Author for Correspondence: ganguly@csmcri.org
ABSTRACT
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The origin of stereoselectivity for [4+2] cycloaddition reaction of methyl methacrylate with
cyclopentadiene was investigated with B3LYPꢀD3(BJ)/6ꢀ31+G(d)//B3LYP/6ꢀ31+G(d) level of theory
in presence of the ionic liquid, 1ꢀethylꢀ3ꢀmethylꢀimidazolium chloride (EMI+Clꢀ) and its acidic
chloroaluminate melt, 1ꢀethylꢀ3ꢀmethylꢀimidazolium heptachlorodialuminate (EMI+Al2Cl7 ). The
ꢀ
reaction of methyl methacrylate with cyclopentadiene was examined in gas phase to rationalize the
ꢀ
effect of the ionic liquid ion pairs EMI+Clꢀ and EMI+Al2Cl7 . The DFT calculated results were found
to be in good agreement with the experimentally observed results. The muchꢀdiscussed hydrogen
bonding effect of the imidazolium cation with the dienophile is less important to govern the
stereoselectivity for the cycloaddition reaction. Atoms in molecules theory (AIM) was used to
examine the role of hydrogen bonding between the EMI+ cation and the methyl methacrylate in the
transition state geometries. The calculated activation barriers with M062X/6ꢀ31+G(d)//B3LYP/6ꢀ
31+G(d) and MP2/6ꢀ311+G(d,p)//B3LYP/6ꢀ31+G(d) levels of theory also predict the similar
exo/endoꢀstereoselectivity trend for the cycloaddition reactions.
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KEYWORDS
DFT, DielsꢀAlder reaction, Cyclopentadiene, Methyl Methacrylate, Ionic Liquid.
INTRODUCTION
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Traditional organic solvents which are generally volatile in nature can be replaced by the
ionic liquids (ILs) to avoid the emission of volatile organic compounds in our environment.1 The use
of water can also be greener and advantageous than ILs, but many organic compounds are difficult to
dissolve in water and disposing of contaminated aqueous streams is expensive1 Though ILs are not
essentially green, some of them are highly poisonous but they can be designed to be environmentally
friendly, with large potential benefits for sustainable chemistry.1 In both academia and in industry, ILs
have a great importance due to their excellent physicochemical properties like nonꢀvolatility, high
intrinsic conductivity, thermal stability, reusability, and powerful solubility.2 Room temperature ionic
liquids (RTILs) often comprise organic cations paired with organic or inorganic anions. Composed
entirely by ions, RTILs represent a very different reaction environment from the other molecular
solvents.2 Studies of organic reactions carried out in RTILs indicate that for many cases RTILs give
better results in terms of rate, selectivity, and yields.3–7
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The Diels–Alder (DA) reaction is one of the most valuable carbonꢀcarbon bond forming
cycloaddition reactions in preparative organic synthesis involving a conjugated diene and a
dienophile.8 It has been used for the diastereoꢀ and regioselective generation of sixꢀmembered rings
with up to four stereogenic centres in a concerted or stepwise process.9 DA reactions are extensively
used for the production of different kind of products like pharmaceutical drugs, agrochemical
compounds, flavours and fragrances in industries. Kleemann et al. reported that more than 2400 active
pharmaceutical drugs have been marketed that include a DA cycloaddition in their synthetic
sequence.10,11 Solvents12 and catalysts13–15 have an important role to control the product (PDT) yield
as well as the selectivity for such cycloaddition reactions.
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Recently, the interest has been focused on employing ILs as reaction media of DA
reactions.16–21 Generally solvents have an important role to affect the DA reactions by accelerating the
rate and changing the endo/exo diastereofacial selectivity.12 To obtain a better insight into the
solvation effect of ILs on the rates and stereoselectivities of several DA reactions, quantum chemical
calculations have also been performed at the molecular level.12,20,22,23 The experimental and the
computational studies of the cycloaddition reaction between cyclopentadiene (CP) and methyl
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acrylate (MA) in the chloroaluminate ionic liquids are reported in the literature.24–27 The solvent
effects on the stereoselectivity of reaction of MA, methyl transꢀcrotonate (MC) and methyl
methacrylate (MMA) with CP in the common organic solvents are already reported both by
experimental28 and computational studies.29 In the common organic solvents, MA and MC favour the
endoꢀPDT while MMA favours the exoꢀPDT due to the effect of substituted methyl group30. Recently,
the experimental results showed that the exoꢀselectivity in organic solvent for MMA can be altered to
the endoꢀselectivity in presence of the chloroaluminate ionic liquids with an accelerated rate due to
the catalytic effect of the Lewis acid, AlCl3.31 The origin of such reversal of stereoselectivity in this
case remains unexplored. Herein, we have reported the origin of stereoselectivity of MMA with
cyclopentadiene using density functional theory (DFT) calculations (scheme 1). To examine the
influence of IL (1ꢀethylꢀ3ꢀmethylꢀimidazolium chloride) on the stereoselectivity of MMA with CP in
presence of the acidic AlCl3 melt (1ꢀethylꢀ3ꢀmethylꢀimidazolium heptachlorodialuminate,
ꢀ
EMI+Al2Cl7 ), additional calculations were performed in the absence of ionic liquid ion pairs (Scheme
1).
Exo- isomer
+
CP
MMA
Endo-isomer
Scheme 1. The exo and endo adducts for the cycloaddition of CP with MMA.
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COMPUTATIONAL DETAILS
Full geometrical optimizations were performed in the gas phase employing the B3LYP
functional32,33 with standard 6ꢀ31+G(d) basis set.34 The single point calculations were carried out by
using the Grimme’s B3LYPꢀD3(BJ)/6ꢀ31+G(d) method35 to account the London dispersion energy
with damping functions introduced by Becke and Johnson on the B3LYP/6ꢀ31+G(d) optimized
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geometries. The Gibbs free energies are calculated by the sum of the B3LYPꢀD3(BJ)/6ꢀ31+G(d)
electronic energy values and the B3LYP/6ꢀ31+G(d) thermal corrections at 298 K.36 The additional
single point calculations in the other method like M062X/6ꢀ31+G(d)37 and MP2/6ꢀ311+G(d,p)38 have
also been performed on B3LYP/6ꢀ31+G(d) optimized geometries. The intrinsic reaction coordinate
(IRC)39,40 calculations have been carried out to confirm that all the transition structures are connected
to the related reactants and products. All DFT calculations were performed by using the Gaussian 09
suite of program.41 The atoms in molecules (AIM) calculations were carried out using the wave
functions generated from the B3LYPꢀD3(BJ)/6ꢀ31+G(d)//B3LYP/6ꢀ31+G(d) calculations with the
Multiwfnꢀ3.2.1 suite of program.42
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RESULTS AND DISCUSSION
The ratio of AlCl3 to 1ꢀethylꢀ3ꢀmethylꢀimidazolium chloride greater than 1:1 is generally
ꢀ
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referred to as an acidic melt of IL.24,25 In this acidic melt of chloroaluminate based IL, AlCl4 and
ꢀ
Al2Cl7 are the principal anionic constituents that are confirmed from the 27Al NMR43, Raman44 and
ꢀ
negativeꢀion FAB mass spectra45 analysis. However, the anionic species Al2Cl7 is a halide ion
acceptor which makes the melt acidic in nature.46
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93
ꢀ
EMI+Clꢀ
EMI+Al2Cl7
ꢀ
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95
Figure 1. B3LYP/6ꢀ31+G(d) optimized geometries of EMI+Clꢀ and EMI+Al2Cl7 . All distances are in
Å.
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We have considered the EMI+Al2Cl7 ionꢀpair to examine the selectivity of the cycloaddition reactions
(CP with MMA) in the acidic conditions of the AlCl3 melt of IL. The explicit models of the EMI+Clꢀ
and EMI+Al2Cl7 (Figure 1) have been employed to elucidate the role of IL. We have first carried out
ꢀ
the calculations for reaction between CP and MMA in gas phase (Figure 2). The calculated activation
barrier (ꢁE‡) at B3LYPꢀD3(BJ)/6ꢀ31+G(d)//B3LYP/6ꢀ31+G(d) suggests that the exoꢀselectivity is
preferred for MMA in gas phase (3.4 kJ/mol) (Figure 2) (Table 1) which is qualitatively in agreement
with the experimental observations.28
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exoꢀTS
endoꢀTS
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Figure 2. B3LYP/6ꢀ31+G(d) optimized geometries of exoꢀ and endoꢀ TSs for the reaction of CP with
MMA. All the distances are given in Å.
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Table 1: B3LYPꢀD3(BJ)/6ꢀ31+G(d)//B3LYP/6ꢀ31+G(d)
calculated electronic energies (ꢁE‡) relative to the free
reactants (CP and MMA) for the reaction between CP and
MMA in absence of IL ion pairs. The free energies are given
in parentheses. All energy values are in kJ/mol.
Exo(ꢁE‡)
Endo(ꢁE‡)
0.0 (0.0)
0.0 (0.0)
CP+MMA
TS
44.6 (108.2)
ꢀ91.9 (ꢀ13.6)
48.0 (111.3)
ꢀ93.2 (ꢀ14.3)
PDT
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The calculated exo and endo transition state (TS) geometries are concerted and asynchronous in
nature. The CꢀC bond forming distances in the exoꢀTS are 2.62 and 1.99 Å and in endoꢀTS are 2.63
and 1.99 Å, respectively (Figure 2).
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Moving from the gas phase (no IL ion pairs) to the IL medium, we have preformed the
ꢀ
cycloaddition of CP with MMA using the EMI+Clꢀ and EMI+Al2Cl7 ion pairs. It is reported that the
ionic liquid has an important role on the reaction rate and also on the selectivity of the cycloaddition
reactions through hydrogen bonding (Hꢀbonding) interactions.20,22,47 It is proposed that dienophile
(MMA) first forms a complex with the IL ionꢀpairs (EMI+Clꢀ or EMI+Al2Cl7 ).22 and then the complex
ꢀ
interact with CP to form the cycloadducts. The role of the ILꢀcation on the reaction rate is suggested
to be more important than that of ILꢀanion,22,24 however, it is interesting to examine the effects of
both cation and anion on cycloaddition reactions.23,25,47 It has been reported that 1:1 cation to anion
ratio of the ionic model of 1ꢀethylꢀ3ꢀmethylꢀimidazolium chloride gives reasonable results for the
cycloaddition reaction between CP and MA.25 The 1:2 cation to anion complexes provide larger
deviations from the experiment results and hence the author concluded for 1:1 cation to anion
complexes for reasonable predictions with IL.25 Therefore, we have examined the [4+2] cycloaddition
reaction of methyl methacrylate with cyclopentadiene in presence of the IL (1ꢀethylꢀ3ꢀmethylꢀ
imidazolium chloride) by considering the 1:1 cation to anion ionic model.
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To account the effect of the IL, we first have performed the calculation of the cycloaddition of
CP with MMA in presence of the EMI+Clꢀ ion pair (1:1). For the formation of the exoꢀ and endoꢀ
products in the presence of the ion pairs EMI+Clꢀ, we have located two complexes, exoꢀMMAꢀ
EMI+Clꢀcomplex and endoꢀMMAꢀEMI+Clꢀcomplex respectively (Figure 3). In both these complexes,
ethyl group of the imidazolium cation resides in same site to the approaching of the CP towards the
dienophile (MMA) in the transition states (Figures 3 and 4).
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ExoꢀMMAꢀEMI+Clꢀcomplex
EndoꢀMMAꢀEMI+Clꢀcomplex
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Figure 3. B3LYP/6ꢀ31+G(d) optimized geometries of exoꢀ and endoꢀ MMAꢀEMI+Clꢀcomplexs for the
reaction of CP with MMA. All the distances are given in Å.
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The calculated DFT results reveal that selectivity trends (exo) of MMA with CP are similar to the
absence of ion pair calculations (Table 1 and Table 2).The ionꢀpair EMI+Clꢀ tend to catalyze the
cycloaddition reactions between CP and MMA (Table 2).The calculated activation barriers (ꢁE‡)for
the exoꢀ and the endoꢀTSs of MMA (Figure 4) are 23.0 and 29.4 kJ/mol from their reactant complexes
(Table 2), which are significantly lower compared to the activation barriers calculated in absence of
ion pair (44.6 and 48.0 kJ/mol for exo and endo-TSs respectively).
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exoꢀTS
endoꢀTS
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Figure 4. B3LYP/6ꢀ31+G(d) optimized exo- and endo-TSs for the reaction of CP with MMA in
presence of the EMI+Clꢀ. All the distances are in Å.
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Table 2: B3LYPꢀD3(BJ)/6ꢀ31+G(d)//B3LYP/6ꢀ31+G(d) calculated
electronic energies (ꢁE‡) relative to the isolated CP and MMAꢀ
EMI+Clꢀꢀ complex for the reaction between CP and MMA in
presence of EMI+Clꢀ. The free energies are given in parentheses. All
energy values are in kJ/mol.
Exo(ꢁE‡)
Endo(ꢁE‡)
45.8 (2.5)
0.0 (0.0)
48.1 (2.6)
0.0 (0.0)
Free reactants
CP+(MMA-EMI+Cl- complex)
23.0 (91.5)
29.4 (96.5)
TS
PDT-EMI+Cl- complex
ꢀ93.6 (ꢀ13.5)
ꢀ95.0 (ꢀ14.6)
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The experimental results for the cycloaddition of CP with MMA in presence of IL without any
addition of AlCl3 salt are not available and hence the selectivity cannot be compared for this reaction.
It is to note that we have calculated the other possible transition state structures where, the ethyl group
of the imidazolium cation reside in opposite site to the approach of the CP towards the dienophile
(MMA). However, these transition structures are comparatively higher in energy than the TSs located
in the Figure 4 (See Supporting Information, Figure S1).
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In the higher concentration of the AlCl3 (i.e. more than 50 mol % of AlCl3)25,31 to the
ꢀ
IL (1ꢀethylꢀ3ꢀmethylꢀimidazolium chloride), the anionic species, Al2Cl7 makes the melt acidic in
nature. To account for the effect of the acidic melt of IL on the cycloaddition of CP with MMA, we
ꢀ
have used 1ꢀethylꢀ3ꢀmethylꢀimidazolium heptachlorodialuminate (EMI+Al2Cl7 ) ion pair (1:1) in our
study (Figure 1). Similarly, for the formation of the exoꢀ and endoꢀproducts in presence of the ion
ꢀ
ꢀ
ꢀ
pairs EMI+Al2Cl7 , we have located two MMAꢀEMI+Al2Cl7 complexes e.g., exoꢀMMAꢀEMI+Al2Cl7 ꢀ
ꢀ
complex and endoꢀMMAꢀEMI+Al2Cl7 ꢀcomplex respectively (Figure 5). But, in both these complexes,
ethyl group of the imidazolium cation resides in opposite site to the approaching of the CP towards
the dienophile (MMA) in the transition states (Figures 5 and 6).
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ꢀ
ꢀ
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ExoꢀMMAꢀEMI+Al2Cl7 complex
EndoꢀMMAꢀEMI+Al2Cl7 complex
ꢀ
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Figure 5. B3LYP/6ꢀ31+G(d) optimized geometries of exoꢀ and endoꢀ MMAꢀEMI+ Al2Cl7 complexs
for the reaction of CP with MMA. All the distances are given in Å.
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The calculated results show that the endoꢀselectivity (6.7 kJ/mol) is preferred over the exoꢀselectivity
for MMA (Table 3) which is in good agreement with the reported experimental results.31 The
calculated activation barriers for the exoꢀ (29.9 kJ/mol) and the endoꢀTS (23.2 kJ/mol) are
significantly lower compared to the calculated barriers in the absence of ion pair for MMA (Tables 1
and 3). Therefore, EMI+Al2Cl7 ion pair alters the selectivity trend for MMA with an accelerated
ꢀ
ꢀ
reaction rate (Table 3). In these calculations, it is clear that the counter anions (Clꢀ and Al2Cl7 ) of the
IL medium have played an important role on the stereoselectivity for the cycloaddition of CP with
MMA. The exo and endo transition states calculated with IL ion pairs (both EMI+Clꢀ and EMI+Al2Cl7 )
ꢀ
seems to be more asynchronous compared to the corresponding transition state geometries in absence
of IL. The highly asynchronous transition structures are found in presence of bothEMI+Clꢀ
ꢀ
EMI+Al2Cl7 IL ion pairs (Figures 4 and 6) compared to the absence of the IL ion pairs (Figure 2). We
have calculated the other possible transition state structures in this case also where, the ethyl group of
the imidazolium cation reside on same side to the approach of the CP towards the dienophile (MMA).
These transition state geometries are relatively higher in energy than the TSs obtained (Figure 6) (See
Supporting Information Figure S1).
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exoꢀTS
endoꢀTS
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Figure 6. B3LYP/6ꢀ31+G(d) optimized exo- and endo-TSs for the reaction of CP with MMA in
ꢀ
presence of the EMI+Al2Cl7 . All the distances are in Å.
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Table 3: B3LYPꢀD3(BJ)/6ꢀ31+G(d)//B3LYP/6ꢀ31+G(d) calculated electronic
ꢀ
energies (ꢁE‡) relative to the isolated CP and MMAꢀEMI+Al2Cl7 complex for the
ꢀ
reactions between CP and MMA in presence of EMI+ Al2Cl7 ionꢀpair. The free
energies are given in parentheses. All energy values are in kJ/mol.
Exo (ꢁE‡)
Endo(ꢁE‡)
48.2 (2.4)
44.5 (0.7)
Free reactants
-
CP+( MMA-EMI+Al2Cl7 complex)
0.0 (0.0)
29.9 (96.6)
ꢀ88.9 (ꢀ8.0)
0.0 (0.0)
23.2 (93.6)
ꢀ102.9 (ꢀ21.4)
TS
PDT-EMI+Al2Cl7 complex
-
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ꢀ
The activation barriers calculated with IL ion pairs (both EMI+Clꢀ and EMI+Al2Cl7 ), for the
cycloaddition reaction between MMA and CP is relatively lower compared to the corresponding
barriers calculated in absence of IL. These results support the experimental observations that this
cycloaddition reaction is faster in presence of such IL.31 The computed free energies in all these cases
are also followed the similar trend like the calculated electronic energies at the same level of theory
(Tables 1ꢀ3).
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The computed activation barriers at M062X/6ꢀ31+G(d)//B3LYP/6ꢀ31+G(d) level of theory also
predicts the similar selectivity trend as observed in the B3LYPꢀD3(BJ)/6ꢀ31+G(d)//B3LYP/6ꢀ
31+G(d) level of theory (see Supporting Information, Table S1). Additional calculations performed
with MP2 level of theory also predict the similar trend of selectivity as observed with B3LYPꢀ
D3(BJ)/6ꢀ31+G(d)//B3LYP/6ꢀ31+G(d) level (see Supporting Information, Table S3). We have also
examined the combined implicit and explicit effect of the ionic liquid (1ꢀethylꢀ3ꢀmethylꢀimidazolium
chloride) for this [4+2] cycloaddition reaction by considering the dielectric constant of the
dichloromethane (Ɛ = 7.26) in our calculations.48 The dielectric constant for dichloromethane is close to
the several 1ꢀethylꢀ3ꢀmethylimidazolium based ionic liquids as reported in the literature.48 In this bulk
solvent (PCM model),49 the endoꢀselectivity in the acidic melt of the IL seems to be preferred as
observed in previous calculations (see Supporting Information, Table S2).
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It has been reported that the weak ionꢀpairing in the acidic melt, EMI+ cation is able to
coordinate strongly with MA at the transition state geometries through Hꢀbonding (acidic proton of
EMI+ and carbonyl oxygen of dienophile) and favors the endo TS for the cycloaddition with CP.25
Further, the QM/MM studies also suggest that the Hꢀbonding is important to induce the endoꢀ
selectivity for the cycloaddition of MA with CP.25However, to note that the earlier reports discussed
only one isomer of the reaction with IL ionꢀpair.24,25 Thus, it appears that the role of Hꢀbonding
towards the exo/endoꢀselectivity has not been thoroughly explored for such cycloaddition reactions.
The Hꢀbonding between the acidic proton of EMI+ and the carbonyl oxygen of the dienophile (MMA)
has been observed (~2Å) in the TS geometries of both exo and endo cases for the cycloaddition of
MMA with CP in presence of the ion pairs (Figures 4 and 6). The ion pairs of IL (EMI+Clꢀ and
ꢀ
EMI+Al2Cl7 ) in our study did not show any significant perturbations in the Hꢀbonding distance
between the EMI+ and the dienophiles. The hydrogen bond strengths have been characterized using
the AIM theory.50 We have calculated the electron density, ρ(rc) of the Hꢀbonds between EMI+cation
ꢀ
and MMA for the exoꢀ and the endoꢀTS for the EMI+Al2Cl7 cases where ρ(rc) is a good indicator of
the bond strength.51According to the AIM calculations, the ρ(rc)value of the Hꢀbonding between
acidic proton of the imidazolium cation and carbonyl oxygen of the MMA in exoꢀ (0.021 a.u.) and
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ꢀ
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endoꢀTSs (0.020 a.u.) in the presence of EMI+Al2Cl7 ion pairs are similar in nature (Figure 7). These
calculated results suggest that the Hꢀbonding is not involved in the reversal of the stereoselectivity in
MMA with CP.31
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227
exoꢀTS
endoꢀTS
228
229
Figure 7. AIM analysis of the B3LYP/6ꢀ31+G(d) optimized exoꢀ and endoꢀTSs for the reaction of CP
with MMA in presence of the EMI+Al2Cl7ꢀ. The ρ(rc) values are given in a.u.
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To examine the selectivity trends for the cycloaddition of CP with MMA, we have employed
distortion/interaction model in presence of the ion/ionꢀpairs and in absence of the ionꢀpairs of IL
(Table 4). The distortionꢀinteraction model is used to explain the selectivity of DA reactions.52,53 The
distortionꢀinteraction model divides the activation energy (ꢁE‡) of a reaction into two parts, (i) the
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239
‡
distortion energy (ꢁEd ) depending on ground state strain, and (ii) the interaction energy(ꢁEi‡) which
‡
is dependent on TS electronics i.e. ꢁE‡ = ꢁEd + ꢁEi‡.54–57 In other words, distortion energy can be
defined as the energy required to distort the reactants from the ground state to adopt the transition
state structure, while the interaction energy comes from the interactions between these distorted
reactants in the transition states (mainly, electrostatic and frontier orbital interactions).58
‡
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The distortion energy (ꢁEd ) calculated for the TS geometries seems to play an important role
to control the selectivity of MMA with CP in presence and in absence of ionꢀpair of IL by lowering
the activation barriers (Table 4). Therefore, the distortion energies of the addends are mostly
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responsible to adopt the transition state geometries to control the selectivity of cycloaddition reaction
for MMA with CP.
244
Table
4.
B3LYPꢀD3(BJ)/6ꢀ31+G(d)//B3LYP/6ꢀ31+G(d)
calculated
activation energies (ꢁE‡), transition state interaction (ꢁEi‡) and distortion
‡
energies (ꢁEd ) for the reaction between CP and MMA in all the cases.All
energies are in kJ/mol
‡
ꢁE‡
ꢁEd
ꢁEi‡
44.6
48. 0
23.0
29.4
29.9
23.2
115.6
117.4
118.3
121.5
127.6
119.7
ꢀ71.0
ꢀ69.4
ꢀ95.3
ꢀ92.2
ꢀ97.7
ꢀ96.6
CP+MMAꢀexo
CP+MMAꢀendo
CP+MMA+ EMI+Clꢀexo
CP+MMA+ EMI+ Clꢀendo
CP+MMA+EMI+Al2Cl7ꢀexo
CP+MMA+EMI+Al2Cl7ꢀendo
245
246
The favourable distortion energies for the exo-TS in absence of the IL ion pair is 1.8 kJ/mol (Table 4).
ꢀ
247
248
249
250
251
The lower activation barrier calculated for the endoꢀTS of MMA and CP with EMI+Al2Cl7 has also
been rationalized with the favourable distortion energy (7.9 kJ/mol), which corroborates the
experimental results (Table 4).31 Furthermore, the interaction energies (ꢁEi‡) also contributing to
augment the selectivities for the cycloaddition reaction, however, such interactions are generally
smaller compared to the distortion energies.
252
CONCLUSIONS
253
254
255
256
257
258
259
260
261
This work demonstrates that the origin of stereoselectivity for the [4+2] DA cycloaddition reaction of
CP with MMA in presence of the ionic liquid (1ꢀethylꢀ3ꢀmethylꢀimidazolium chloride) and its acidic
chloroaluminate melt (1ꢀethylꢀ3ꢀmethylꢀimidazolium heptachlorodialuminate) can be rationalized
using DFT calculations. The reversal of stereoselectivity predicted for the cycloaddition of CP with
MMA in presence of the AlCl3 based acidic melt of the ionic liquid (1ꢀethylꢀ3ꢀmethylꢀimidazolium
chloride) has been found to be in good agreement with the experimental observations. The exoꢀTS is
favored over the corresponding endoꢀTS by 3.4 kJ/mol in absence of the ionic liquid, while the endoꢀ
TS is favored over the corresponding exoꢀTS by 6.7 kJ/mol in presence of the acidic melt of the ionic
liquid at B3LYPꢀD3(BJ)/6ꢀ31+G(d)//B3LYP/6ꢀ31+G(d) level of theory. The M062X/6ꢀ
13

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262
263
264
265
266
267
268
269
270
271
272
273
274
31+G(d)//B3LYP/6ꢀ31+G(d) and MP2/6ꢀ311+G(d,p)//B3LYP/6ꢀ31+G(d) levels of theory also predict
the similar favorable exoꢀTS in gas phase calculation (absence of the ion pair) and the favorable endoꢀ
TS in presence of the acidic melt of the ionic liquid ion pair for the cycloaddition of CP with MMA.
The AIM calculations reveals that the hydrogen bonding of ionic liquid cation with the dienophiles is
less important to govern the stereoselectivity in this case which is confirmed from the electron density
ρ(rc) calculations. The Distortion/interaction model calculations showed that the stereoselectivity is
governed by the distortion energies of the addends involved in the cycloaddition reaction in presence
of ionic liquid ion pair and in absence of such ionꢀpairs. The favorable distortion energy (7.9 kJ/mol)
of the endoꢀTS in the acidic melt of the ionic liquid induces to reverse the selectivity from exo to endo
products. The DFT calculations further revealed that the role of counter ion of acidic melt is crucial to
induce the change in the stereoselectivity of MMA with CP. The Computational study performed
here to investigate the stereoselectivity of MMA with CP in presence of ionic liquid would be helpful
to guide such reactions and to design the new products.
275
SUPPLEMENTARY MATERIAL
276
277
Supplementary material is available with the article through the journal Web site at
http://nrcresearchpress.com/doi/suppl/
278
Acknowledgments
279
280
281
282
283
CSIRꢀCSMCRI Communication No. 101/2013. The authors thank DST (New Delhi) and MSM, SIP,
CSIR (New Delhi) for financial support. One of the authors' D.S. thanks UGC (India) for fellowship.
D.S. is also thankful to AcSIR for enrolment in the Ph.D. program. The authors thankfully
acknowledge the computer resources provided by the CSIRꢀNCL, Pune (India) and the CSIRꢀ
CMMACS, Bangalore (India). We thank the anonymous reviewers for their valuable suggestions.
284
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