Captodative substitution induced acceleration effect towards 4π electrocyclic ring-opening of substituted cyclobutenes

Abstract

The captodative substitution effect towards 4π electrocyclic ring-opening of substituted cyclobutenes is investigated using the B3LYP/6-31+G(d) method. For most of the cases, the activation free energy for the ring-opening of substituted cyclobutenes is lower than for the unsubstituted cyclobutenes and for several captodative substitution patterns, it differs by more than 15.0 kcal mol⁻¹. The lowest activation energy barrier is computed for trans-3-C(O)CH₃–4-NH₂ substituted cyclobutene, which is remarkably 23.7 kcal mol⁻¹ lower than for the unsubstituted cyclobutene. In addition to this, an extra acceleration effect exerted by the captodative substitution is probed through energetic analyses.

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1 Introduction

4π electrocyclisation is an extensively used approach to synthesise complex carbocyclic compounds of significant biological relevance.^1,2 It is a powerful methodology that proceeds with a predictable and an excellent regio- and stereocontrol, explained by Woodward–Hoffmann's rules.³ These rules explain the stereochemical outcome of an electrocyclic transformation by recognising the symmetry of frontier orbitals. Thermal 4π electrocyclic ring-opening of substituted cyclobutenes is a common strategy that has been incorporated towards the synthesis of several cytotoxic molecules with profound structural complexity such as verrucarin A (1)⁴ and pheromones like periplanone-B (2,⁵ Fig. 1). Also, numerous synthetically significant building blocks such as polyether 3 (ref. 6) and structurally diversified dienes⁷ have been efficiently accessed through this procedure. Moreover, this procedure can be strategically applied to prepare polysubstituted cyclobutane containing bioactive natural products.⁸ Depending on the geometry of substituted cyclobutene and inward/outward rotation (torquoselectivity) of the substituents (R₁ and R₂) located at the site of ring-opening of cyclobutene, this symmetry-allowed approach can be used to generate all possible geometric isomers of butadiene (Fig. 2). This transfer of stereochemical features from cyclobutene to corresponding butadiene is governed by torquoselectivity rules.^9,10 There is a general preference of diene substrates for an all trans-geometrical configuration that implies an isomerisation of initially formed product. This is a common situation for the cases in which the substituents (R₁ and R₂) are an electronically antagonistic pair.

Fig. 1 Representative molecules synthesised by employing 4π electrocyclic ring-opening of substituted cyclobutenes.

Fig. 2 4π electrocyclic ring-opening of cis- and trans-cyclobutenes; towards the synthesis of 1,3-butadienes.

The art of synthesis has been revolutionised by quantum chemical calculations and these theoretical tools are inevitably associated to gain an insightful information towards the elucidation of reaction mechanisms, molecular properties and chemical reactivity descriptors.¹¹ Application of computational investigation is, indeed, a time and cost effective approach, which is ubiquitous in electrocyclic transformations.

Normally, electrocyclisation reactions require a huge activation energy to overcome and due to this, high temperature is indispensable to activate the reactions. Several successful attempts have been reported in which the activation barriers for chemical transformations have been significantly reduced by introducing a captodative substitution.¹² This particular kind of substitution illustrates a combined effect of electron withdrawing (captor) and electron donating (dative) substituents attached to the reaction sites and exerts a substantial influence on the rates of reactions. It has been explicitly described for thermal disrotatory 6π electrocyclisation of 1,3,5-hexatrienes¹³ and amidotrienes,¹⁴ Diels–Alder cycloadditions of 2-(tert-butylthio)acrylonitrile,¹⁵ α-(methylthio)acrylonitrile¹⁶ and 1-cyanoenamines,¹⁷ for the preparation of 1,1′-captodative butadienes¹⁸ and cyclopropanes¹⁹ and for [2 + 2] cycloaddition reactions of olefins.²⁰ In addition to this, captodative substitution has found its applications in the field of radical chemistry²¹ and numerous theoretical investigations²² have also been reported for this. It is worth mentioning that not all the captodative substitution patterns lead to lower the energy barriers and the acceleration effect is basically related with the proper location of electron donor and acceptor substituents in a molecule. However, a systematic investigation of captodative substitution effect is instrumental to envisage the chemical reactivity and provides a very useful information about the reaction profile.

Inspired by the successful application of captodative substitution in chemical reactions, its effect on the electrocyclic ring-opening of variously functionalised cyclobutenes has been computed. An array of synthetically significant substituents with varying structural features were selected; CH₃, NH₂ and OH groups are typical electron donors, F is a halogen atom and C(O)CH₃, CN and NO₂ are classical electron withdrawing groups. The location of these substituents on cyclobutene skeleton produces a substantial effect on the activation free energies and it has been precisely documented in this paper, which provides a real insight towards electrocyclic ring-opening of disubstituted cyclobutenes via captodative substitution.

2 Results and discussion

2.1 Ring-opening of monosubstituted cyclobutenes

As expected, thermal conrotatory 4π electrocyclic ring-opening of cyclobutene requires substantial activation barrier (32.5 kcal mol⁻¹, entry 1, Table 1). Gratifyingly, the barrier calculated at the B3LYP level of theory (32.5 kcal mol⁻¹) is in agreement with the experimental barrier reported by Goldstein and colleagues (32.5 kcal mol⁻¹).²³ Moreover, it has been found that the computational method (B3LYP) used in this study generates reliable activation barriers for ring-opening of cyclobutene.^10g In general, installation of electron donating groups and halogen atom at C3 position of cyclobutene decreases the energy barrier. For CH₃ group (entry 2), it is 3.3 kcal mol⁻¹ less than the unsubstituted cyclobutene. A lower energy barrier of 18.3 kcal mol⁻¹ is noticed for NH₂ group and it gradually increases in moving from left to right in the periodic table; 23.2 and 27.7 kcal mol⁻¹ for OH and F substituents respectively (entries 3–5, Table 1). This increase in the computed activation barrier may be ascribed to the destabilisation of the transition states caused by the presence of electron lone pairs on the substituents at C3 position. The observed energy barriers seem directly related with the electronegativity and a strong positive free energy linear relationship is obtained by plotting the energy barriers of NH₂, OH and F substituents against their corresponding electronegativity values (see Fig. 1a of ESI†). Notably, the bond distances between the carbon atoms (C3 and C4) in the related transition states also gradually decrease from NH₂ to F substituents (see Fig. 1b of ESI†).²⁴

Table 1 Free energy barriers (ΔG^‡), energies of reaction (E_R) and bond distances between C3 and C4 atoms for ring-opening of cyclobutene (entries 1 and 9) and monosubstituted cyclobutenes (entries 2–8 and 10–16)

Entry	R1	ΔG^‡^a^,^b	ER^a^,^b	C3–C4^b^,^c	ΔG^‡^a^,^d	ER^a^,^d	C3–C4^c^,^d	Entry	R2	ΔG^‡^a	C3–C4^c
a Energies are in kcal mol^−1 and for detailed information see ESI.b Values are for outward rotation of substituents.c Bond distances are from the corresponding transition states and the values are in Å.d Values are for inward rotation of substituents.
1	H	32.5	−11.4	2.144	32.5	−11.4	2.143	9	H	32.5	2.144
2	CH3	29.2	−13.6	2.156	36.6	−11.7	2.194	10	CH3	34.0	2.156
3	NH2	18.3	−19.2	2.133	37.9	−18.5	2.189	11	NH2	32.9	2.149
4	OH	23.2	−14.3	2.129	39.6	−15.0	2.218	12	OH	32.8	2.170
5	F	27.7	−9.6	2.126	42.1	−10.2	2.178	13	F	32.9	2.178
6	C(O)CH3	27.8	−16.1	2.142	29.9	−12.6	2.187	14	C(O)CH3	33.2	2.153
7	CN	27.9	−14.6	2.144	32.6	−14.1	2.182	15	CN	33.3	2.153
8	NO2	29.1	−11.8	2.128	35.5	−7.8	2.186	16	NO2	31.9	2.165

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Presence of electron withdrawing groups at C3 position of cyclobutenes also decreases the activation barriers (entries 6–8, Table 1). As compared to the unsubstituted cyclobutene, these substituents lead to a noticeable decrease in the activation barriers (up to 4.7 kcal mol⁻¹). This decrease in the activation energy is related to the electron withdrawing ability of the substituents; higher the ability to withdraw electrons, higher is the free energy barrier. Also, a high positive linear relationship is observed for the activation barriers of electron withdrawing bearing cyclobutenes and the corresponding bond distances between C3 and C4 atoms in the transition states (see Fig. 1c of ESI†).²⁴

Both OH and C(O)CH₃ substituents exist in two possible conformations around the bond between the substituted cyclobutenes and the substituents. In such a situation, low energy conformation of the transition state could possibly be different from the low energy ground state²⁵ and it has been accounted for both substituents (entries 4 and 6, Table 1).²⁶ Not surprisingly, effect of substituents located at C3 position on torquoselectivity suggests that an outward rotation of substituents leads to lower energy barriers as compared to inward rotation (entries 1–8, Table 1). Also, the bond distances between C3 and C4 atoms in the transition states are comparatively longer for inward rotation of substituents.

At this juncture, a comparative investigation between the activation free energy of the ring-opening of monosubstituted cyclobutene and reaction exoergonicity was envisaged. There are literature reports which describe a correlation between the both; if the reaction mechanism is unchanged, more exothermic reactions generally proceed with low energy barriers (see ESI for details†).²⁷ The results are summarised in Table 1, which provide interesting information and correlations (see Fig. 3 of ESI†).

It is evident from these results that the structural features of substituents play a decisive role. Going from NH₂ to F substituents (entries 3–5, Table 1), the energy barriers gradually increase and as anticipated exothermicity is gradually decreased. Despite of the fact that there is a slight difference between the activation barriers for the compounds bearing electron withdrawing groups at C3 positions of cyclobutenes (entries 6–8, Table 1), a noticeable difference in reaction exoergonicity is computed for these substrates.

Electrocyclic ring-opening of C1 substituted cyclobutenes (entries 10–16, Table 1) require higher energy barriers compared to the situations when these substituents are present at C3 positions (entries 2–8, Table 1). It is obvious that the substituents at C1 positions of cyclobutenes remain conjugated with the endocyclic olefinic bond, while the conjugation is lost when these substituents are located at C3 positions. It is plausible to rationalise that presence of either electron donating or withdrawing species at C1 position may lead to destabilisation of the transition state due to conjugation that, in return, increases the activation barriers. Overall, it is evident that monosubstitution of cyclobutene at C3 position decreases the activation free energy for the ring-opening as compared to the free energy barrier of unsubstituted cyclobutene, regardless of whether there is an electron donating or accepting substituent. Contrary to this, a slight increase in the activation energy is observed for the electrocyclic ring-opening of C1 substituted cyclobutenes.

2.2 Ring-opening of disubstituted cyclobutenes

A comprehensive account of calculated energy barriers for the ring-opening of disubstituted cyclobutenes is summarised in Table 2. It describes all possible combinations for the considered substituents and provides strong evidence towards the captodative substitution effect. An interpretation of these results appear somewhat intricate however following points can be clearly seen:

Table 2 Activation free energies (ΔG^‡) for electrocyclic ring-opening of variously functionalised disubstituted cyclobutenes. The values are in kcal mol⁻¹ and for detailed information see ESI

	R2 = CH3	R2 = NH2	R2 = OH	R2 = F	R2 = C(O)CH3	R2 = CN	R2 = NO2
1,4-Disubstituted cyclobutenes
R1 = CH3	31.6	30.9	30.2	30.0	30.0	29.7	28.9
R1 = NH2	21.0	20.8	24.0	20.2	18.3	17.4	16.8
R1 = OH	25.5	27.3	26.2	25.1	23.0	23.2	24.7
R1 = F	29.4	29.5	30.2	29.5	28.9	28.6	28.3
R1 = C(O)CH3	28.7	25.6	28.9	29.2	30.9	29.3	29.1
R1 = CN	29.3	26.8	28.2	27.9	29.8	29.0	28.5
R1 = NO2	31.0	28.1	30.6	30.6	31.0	31.6	32.4
1,3-Disubstituted cyclobutenes
R1 = CH3	30.8	29.8	29.3	28.9	29.8	29.8	28.0
R1 = NH2	20.0	18.6	17.5	16.8	18.8	17.6	15.8
R1 = OH	24.9	23.9	22.8	22.3	23.7	23.0	21.1
R1 = F	29.6	29.5	28.5	27.8	28.3	28.1	26.3
R1 = C(O)CH3	28.6	28.6	28.5	28.1	26.9	27.9	26.6
R1 = CN	29.7	29.1	28.9	28.7	28.4	28.7	27.2
R1 = NO2	31.2	31.2	31.0	30.6	29.7	30.5	29.0
trans-3,4-Disubstituted cyclobutenes
R1 = CH3	26.5	16.8	21.3	25.3	23.8	24.2	24.7
R1 = NH2		12.3	15.7	16.0	8.8	10.7	10.0
R1 = OH			17.4	20.6	16.1	17.2	17.6
R1 = F				24.2	22.1	22.5	23.7
R1 = C(O)CH3					22.5	23.0	23.0
R1 = CN						22.8	23.0
R1 = NO2							26.9
1,2-Disubstituted cyclobutenes
R1 = CH3	35.1	33.5	34.2	33.9	34.4	35.0	34.0
R1 = NH2		27.2	30.1	31.3	35.1	35.6	36.5
R1 = OH			31.0	32.4	34.3	34.7	33.7
R1 = F				32.2	33.5	34.1	32.2
R1 = C(O)CH3					29.7	33.7	31.8
R1 = CN						34.2	32.7
R1 = NO2							28.3

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(1) In case of 1,4-disubstituted cyclobutenes, presence of NH₂ substituent at C4 position significantly lower the energy barriers and the lowest one is computed for 1-NO₂–4-NH₂ substituted compound, which differs by 15.7 kcal mol⁻¹ from unsubstituted cyclobutene. This reduction in the energy barrier is not the consequence of a true captodative substitution as NO₂ substituent does not influence the site of σ bond breaking; the effect seems rather approximately additive. The additive effect is a reflection of the difference in the activation barriers between the disubstituted cyclobutene and corresponding monosubstituted cyclobutenes. The energy barrier for 3-NH₂ substituted compound is 18.3 kcal mol⁻¹, which is 14.2 kcal mol⁻¹ lower than the unsubstituted cyclobutene. Similarly, there is a difference of 0.6 kcal mol⁻¹ between the free energy values of 1-NO₂ substituted and unsubstituted cyclobutenes. The additive effect of these two substituents is 14.8 kcal mol⁻¹, which explains a reduction of 15.7 kcal mol⁻¹ in the barrier height for 1-NO₂–4-NH₂ substituted cyclobutene, compared to unsubstituted cyclobutene. Similar trend is observed for other examples such as the decrease in activation barrier for 1-NH₂–4-NH₂ substituted compound (11.7 kcal mol⁻¹) is approximately additive (14.2 kcal mol⁻¹ for 3-NH₂ and −0.4 kcal mol⁻¹ for 1-NH₂ substituted cyclobutenes produce an additive effect of 13.8 kcal mol⁻¹).

(2) The energy trends observed for 1,3-disubstituted cyclobutenes are identical to 1,4-disubstituted systems. However, a more pronounced additive effect is noticed for the examples, in which, NH₂ group is located at C3 positions. The lowest activation energy is calculated for 1-NO₂–3-NH₂ (15.8 kcal mol⁻¹; a consequence of an approximate additive effect). Notably, all the combinations described for 1,4- and 1,3-disubstituted cyclobutenes require lower energy barriers than the unsubstituted cyclobutene.

(3) Regarding trans-3,4-disubstituted model systems, a perfect captodative substitution effect is recorded for the situations where both electron withdrawing and donating groups are located on the carbons (C3 and C4) involved in the ring-opening of cyclobutenes. Due to an additive effect as explained before, a decrease in the activation barriers is noticed for several disubstituted compounds. However, a remarkable acceleration effect towards electrocyclic ring-opening of cyclobutenes is found for the captodative substitution patterns, in which, the reduction in the activation barriers is significantly lower than the additive effect mediated expected values. The lowest energy barrier of 8.8 kcal mol⁻¹ is computed for trans-3-C(O)CH₃–4-NH₂ disubstituted cyclobutene, which differs by 23.7 kcal mol⁻¹ from that of unsubstituted cyclobutene. For this particular case, an additive effect can only provide a reduction of 4.3 kcal mol⁻¹. For most of the cases, the reduction in the barrier for captodative substitution patterns is more than 15.0 kcal mol⁻¹.

(4) In general, the patterns involving 1,2-disubstitution proceed via high activation free energy and an additive effect exerted by the substituents in the opposite direction is observed. For several substitution patterns, the activation energy is 2.5 kcal mol⁻¹ higher than the unsubstituted cyclobutene. In case of 1-NH₂–2-NO₂ substituted compound, the barrier should be 4.2 kcal mol⁻¹ lower than the calculated, if additive effect is operative. This unusual increase in the activation barrier may be ascribed to an extended conjugation across π bond, particularly for 1,2-disubstitution combinations where both electron withdrawing and donating groups are located across π bond. It also suggests that the barriers reflect a similar effect as observed for C1 monosubstituted cyclobutenes.

3 Energetic analyses for captodative substitution effect

A comprehensive study of the captodative substitution pattern reveals that electrocyclic ring-opening of disubstituted cyclobutenes is possible with lower energy barriers up to 8.8 kcal mol⁻¹. To further investigate the effect of captodative substitution, extra energetic effect (E_extra) as a result of captodative substitution over monosubstitution for possible captodative substitution patterns is computed by using eqn (1) (the subscripts indicate whether the energy barrier is for un-, mono- or disubstituted cyclobutenes and EWG stands for electron withdrawing group while EDG is for electron donating group).

E_extra = ΔG^‡_EWG,EDG + ΔG^‡_H,H − ΔG^‡_EWG,H − ΔG^‡_EDG,H (1)

A positive value of E_extra is a reflection of less prominent acceleration effect caused by both substituents together as compared to their individual capability of acceleration. Contrary to this, if E_extra is negative then the acceleration effect of both substituents together is more pronounced than their individual capacity of acceleration. An accelerated captodative substitution effect exerted by C(O)CH₃ as electron withdrawing substituent and CH₃, NH₂ and OH as electron donating groups lead to reduce the energy barriers and it has been reported in Table 3. It can be clearly seen that the highest E_extra negative value is calculated for trans-3-C(O)CH₃–4-NH₂ substituted cyclobutene (entry 7, Table 3), which provides an extra acceleration effect to the ring-opening of cyclobutene. The activation free energy for trans-3-C(O)CH₃–4-NH₂ cyclobutene is 8.8 kcal mol⁻¹, which is remarkably 23.7 kcal mol⁻¹ lower than the unsubstituted cyclobutene. Additionally, energy of reaction (E_R) is also calculated, which provides a weak correlation between the activation barriers for the ring-opening of disubstituted cyclobutenes and their corresponding reaction exoergonicity values.

Table 3 Energetic analyses for the captodative substitution effects of an electron acceptor [C(O)CH₃] and electron donors (CH₃, NH₂, OH) in the electrocyclic ring-opening of disubstituted cyclobutenes

Entry	Substituents	ΔG^‡^a	Eextra^a	ER^a
a Energies are in kcal mol^−1 and for detailed information see ESI.
1	1-C(O)CH3–4-CH3	30.0	0.1	−3.9
2	1-C(O)CH3–3-CH3	29.8	−0.1	−9.1
3	trans-3-C(O)CH3–4-CH3	23.8	−0.7	−18.7
4	1-C(O)CH3–2-CH3	34.4	−0.3	−1.8
5	1-C(O)CH3–4-NH2	18.3	−0.7	−13.9
6	1-C(O)CH3–3-NH2	18.8	−0.2	−15.7
7	trans-3-C(O)CH3–4-NH2	8.8	−4.8	−26.8
8	1-C(O)CH3–2-NH2	35.1	1.5	1.2
9	1-C(O)CH3–4-OH	23.0	−0.9	−11.2
10	1-C(O)CH3–3-OH	23.7	−0.2	−10.3
11	trans-3-C(O)CH3–4-OH	16.1	−2.4	−20.7
12	1-C(O)CH3–2-OH	34.3	0.8	−1.1

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A similar relationship between the activation free energy and extra energetic effect (E_extra), as well as between the energy barriers and the energy of the reactions (E_R) is noticed for the captodative substitution patterns involving CN as electron withdrawing and CH₃, NH₂ and OH substituents as electron donating groups. Due to captodative substitution, highly negative E_extra values are observed for trans-3,4-disubstituted combinations (entries 3, 7 and 11, Table 4) so the acceleration effect is more effective and lower energy barriers are required for these combinations. The lowest energy barrier (10.7 kcal mol⁻¹) is noted for the ring-opening of trans-3-CN–4-NH₂ substituted cyclobutene (entry 7), which has the highest negative values for E_extra and E_R.

Table 4 Energetic analyses for the captodative substitution effects of an electron acceptor (CN) and electron donors (CH₃, NH₂, OH) in the electrocyclic ring-opening of disubstituted cyclobutenes

Entry	Substituents	ΔG^‡^a	Eextra^a	ER^a
a Energies are in kcal mol^−1 and for detailed information see ESI.
1	1-CN–4-CH3	29.7	−0.3	−10.2
2	1-CN–3-CH3	29.8	−0.2	−10.0
3	trans-3-CN–4-CH3	24.2	−0.4	−17.2
4	1-CN–2-CH3	35.0	0.2	−2.7
5	1-CN–4-NH2	17.4	−1.7	−20.7
6	1-CN–3-NH2	17.6	−1.5	−17.0
7	trans-3-CN–4-NH2	10.7	−3.0	−24.6
8	1-CN–2-NH2	35.6	1.9	1.6
9	1-CN–4-OH	23.2	−0.8	−11.8
10	1-CN–3-OH	23.0	−1.0	−11.6
11	trans-3-CN–4-OH	17.2	−1.4	−18.4
12	1-CN–2-OH	34.7	1.1	−2.5

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Finally, an energetic analyses for the captodative substitution effect exerted by NO₂ as electron acceptor and CH₃, NH₂, OH as electron donors is calculated and the results are presented in Table 5, which are in good agreement with other findings of this study. Again, highest negative E_extra value is computed for trans-3-NO₂–4-NH₂ substituted cyclobutene (entry 7, Table 5) with lowest energy barrier. As expected and explained before, this reaction is highly exothermic due to an inverse relationship between the activation barrier and the reaction exoergonicity. This highlights the significance of quantum chemical calculations to identify the optimum substitution pattern for a rapid 4π electrocyclic ring-opening of substituted cyclobutenes.

Table 5 Energetic analyses for the captodative substitution effects of an electron acceptor (NO₂) and electron donors (CH₃, NH₂, OH) in the electrocyclic ring-opening of disubstituted cyclobutenes

Entry	Substituents	ΔG^‡^a	Eextra^a	ER^a
a Energies are in kcal mol^−1 and for detailed information see ESI.
1	1-NO2–4-CH3	28.9	0.3	−8.9
2	1-NO2–3-CH3	28.0	−0.6	−11.6
3	trans-3-NO2–4-CH3	24.7	−1.1	−14.9
4	1-NO2–2-CH3	34.0	0.6	−1.8
5	1-NO2–4-NH2	16.8	−0.9	−25.0
6	1-NO2–3-NH2	15.8	−1.9	−19.2
7	trans-3-NO2–4-NH2	10.0	−4.9	−24.0
8	1-NO2–2-NH2	36.5	4.2	6.8
9	1-NO2–4-OH	24.7	2.1	−8.4
10	1-NO2–3-OH	21.1	−1.5	−13.8
11	trans-3-NO2–4-OH	17.6	−2.2	−16.2
12	1-NO2–2-OH	33.7	1.5	−2.6

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4 Conclusions

An accelerated effect exerted by the captodative substitution towards 4π electrocyclic ring-opening of cyclobutene is described. Following salient conclusions can be drawn from this study:

(1) Regardless of the specific structural features of the substituents, monosubstitution at C3 position of cyclobutene decreases the energy barrier for the ring-opening as compared to the activation free energy of unsubstituted cyclobutene. For mesomerically electron donating species, the effect is more pronounced and the barrier is reduced up to 14.2 kcal mol⁻¹ as noticed for NH₂ substituent. Electron withdrawing groups lead to a reduction in the barrier up to 4.7 kcal mol⁻¹. Also, outward rotation of substituents located at C3 position of cyclobutene is energetically favoured over inward rotation of the substituents.

(2) Compared to unsubstituted cyclobutene, presence of considered substituents at C1 position of cyclobutene renders an insignificant impact on the activation barriers of C1 substituted cyclobutenes.

(3) In general, the activation free energies for the ring-opening of 1,4- and 1,3-disusbtituted cyclobutene systems proceed with lower energy barriers, which reflect an additive effect of the corresponding monosubstituted cyclobutenes.

(4) An extra energetic effect (E_extra) as a result of captodative substitution over monosubstitution is reported for the substitution patterns involving an electron acceptor and electron donor. This effect is ubiquitous for trans-3,4-disubstituted captodative combinations, which require remarkably lower activation barriers. The lowest energy barrier of 8.8 kcal mol⁻¹ is computed for trans-3-C(O)CH₃–4-NH₂ substituted cyclobutene, which is 23.7 kcal mol⁻¹ lower than the unsubstituted cyclobutene.

(5) The activation barriers for 1,2-disubstituted cyclobutenes are slightly higher than the unsubstituted cyclobutene and an additive effect in an opposite direction is observed for several substitution pattern.

(6) Finally, a weak correlation is observed between the activation barriers for the ring-opening of substituted cyclobutenes and the reaction exoergonicity.

5 Methods

All calculations were performed with the Gaussian 09W programme²⁸ and the results were produced with GaussView 5.0. Density functional theory (DFT)²⁹ calculations using the B3LYP functional³⁰ were used to locate all the stationary points involved. Geometries were optimised at B3LYP/6-31+G(d) level of theory.³¹ The frequency calculations were run at the same level of theory to confirm each stationary point to be either a minimum or a transition structure. Representative transition states were also linked to their corresponding minima through the intrinsic reaction coordinate (IRC)³² calculations (see ESI for details†), which confirm the connection of transition structures with the reactants and products. Gibbs free energy values were computed from the optimised geometries at 298.15 K and are not corrected.

Acknowledgements

The author gratefully acknowledges the support offered by the King Faisal University, Saudi Arabia. Also, K. Ayub (COMSATS Institute of Information Technology, Pakistan) is thanked for the technical discussions.

Notes and references

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c5ra26590h

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