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Mar 27, 2017 - Department of Chemistry, University of Idaho, 875 Perimeter Drive, Mail Stop 2343, Moscow, Idaho 83844-2343, United States. •S Suppor...
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The Role of Strain in the Homoaromatization of Semibullvalenes Richard Vaughan Williams,* Abdullah G. Al-Sehemi,† Amanda K. Meier, Zachary Z. Brown, and John R. Armantrout Department of Chemistry, University of Idaho, 875 Perimeter Drive, Mail Stop 2343, Moscow, Idaho 83844-2343, United States S Supporting Information *

ABSTRACT: The low activation barrier to the Cope rearrangement of semibullvalenes has been attributed to the inherent ring-strain of this nucleus. Appropriate, Dewar−Hoffmann, substitution of semibullvalene results in the stabilization of the transition state and a further lowering of the Cope barrier. An alternative proposal for lowering/eliminating this barrier is the use of strain to destabilize the localized semibullvalene. Using density functional and Hartree−Fock calculations, we predict that additionally straining the semibullvalene nucleus, by small ring annelations, will lead to a lowering of the Cope barrier and ultimately to ground state neutral homoaromatics.



INTRODUCTION Fascination with the Cope rearrangement remains unabated.1,2 An active area of focus is on reducing, or even eliminating, the activation barrier to the Cope rearrangement (particularly in homotropilidenes, e.g., homotropilidene (1) itself), ultimately resulting in a homoaromatic ground state species.3 The degenerate Cope rearrangement of the bridged homotropilidene, semibullvalene 2, proceeds through the delocalized aromatic transition state (TS) 2deloc with an exceedingly low activation barrier.4 Calculations by Dewar and Lo and Hoffmann and Stohrer suggest that substitution with electron-withdrawing groups at the 2,4,6,8 positions and/or electron-donating groups at the 1,5 positions of the semibullvalene nucleus would stabilize the TS reducing, or perhaps even eliminating, the barrier to the rearrangement.5,6 Many Dewar−Hoffmann semibullvalenes have been synthesized and, as predicted, the activation barrier to the Cope rearrangement was lowered.7−9 However, no example has yet been prepared in which the delocalized homoaromatic species, analogous to 2deloc, becomes the ground state. However, it should be noted that Quast’s methano-bridged homotropilidene, 2,6-dicyano4,8-diphenylbarbaralane (3) forms a homoaromatic ground state solvate in N,N′-dimethylpropylene urea (Scheme 1).10 The role of strain in increasing the rate of the Cope rearrangement has been appreciated since the early sixties when Vogel and Doering and their co-workers postulated that cisdivinylcyclopropane 4 defied isolation, even at −40 °C, because it underwent extremely facile Cope rearrangement to give 1,4cycloheptadiene (5).2,11,12 Their rationalization for the tremendous rate acceleration, compared with the parent 1,5hexadiene, was relief of ring strain (partial cleavage of the cyclopropyl bond) in the TS. Subsequently 4 has been isolated and its kinetic parameters determined (Table 1).13 Vögtle et al. similarly invoked strain to explain the enhanced Cope rearrangement in the bridged biallyls 6 and proposed that the corresponding rearrangement of the bis-bridged systems 7 would also be accelerated by strain (Scheme 2) .14 Progressing © 2017 American Chemical Society

from cis-divinylcyclopropane (4) to homotropilidene (1) again results in a degenerate Cope rearrangement with a concomitant reduction in the activation barrier due to restricted conformational freedom compared with 4. Bridging the homotropilidene moiety and locking it in a preferred (boat-like) conformation for the Cope rearrangement, as in semibullvalene (2), bullvalene (8), dihydrobullvalene (9), barbaralane (10), and barbaralone (11) further enhances the rate of this rearrangement (Table 1, Scheme 3). Doering et al., in commenting on the fact that the Cope rearrangement in barbaralone 11 is, as predicted by them, much faster than that in homotropilidene 1, state “That strain may be a significant factor in the acceleration is indicated by the very rapid rate of rearrangement found in semibullvalene”.15 Similarly, Dewar and Schoeller and Iwamura et al. invoked strain as a contributing factor in the ease of the Cope rearrangement of bridged-homotropilidenes.16 More recent calculations confirm these intuitive recognitions of the crucial role played by strain in determining the relative rates of a series of Cope rearrangements.17,18 The results from B3LYP/ 6-31G* calculations by Borden et al. showed that the cyclopropane unit in semibullvalene 2 is significantly more strained than it is in bullvalene 8, dihydrobullvalene 9, or barbaralane 10.18 It has been suggested, from the results of a quantum theory of atoms-in-molecules (QTAIM) study, that the extremely low barrier to the Cope rearrangement of 2 results from the stabilization of atoms and electronic delocalization not the release of ring strain on the opening of the three-membered ring in the ground state of 2.19 However, this stabilization could equally be viewed as a release of strain, not necessarily the classical ring strain of a three-membered ring, but a more subtle overall molecular property, in the ground state of 2 on proceeding to 2del. An alternative to the Dewar−Hoffmann approach to realizing a homoaromatic semibullvalene is, corresponding with the Received: January 7, 2017 Published: March 27, 2017 4136

DOI: 10.1021/acs.joc.7b00043 J. Org. Chem. 2017, 82, 4136−4147

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The Journal of Organic Chemistry Scheme 1

Table 1. Free Energies of Activation (ΔG‡, kcal/mol) for the Cope Rearrangement of 1, 2, 4, 8, 9, 10, and 11a,b compound

ΔG‡

temp, °C

1 2 4 8 9 10 11

13.7 5.5 ∼20 12.8 9.5 7.8 9.6

−35 −143 5−20 100 −40 −77 −55

Scheme 4

Scheme 5

a

For consistency and to allow internal comparison all values are taken from the same source. bReference 4a.

Scheme 2 Paquette and Vogel groups studied the effects of medium ring annelation across one terminus of the semibullvalene nucleus (14).22,23 The position of the Cope equilibrium was altered; however, not surprisingly, the localized geometries (14, 14′) were still found to be the ground states (Scheme 6). Paquette Scheme 3

Scheme 6

strain induced rate enhancement of the Cope rearrangement detailed above, to use strain-induced destabilization of the localized forms (2loc, 2′loc) to give a ground state homoaromatic species analogous to 2deloc.7−9 Analogous to enzymatic catalysis, straining the semibullvalene nucleus would raise the energy of the ground state and potentially stabilize the delocalized form, akin to how enzyme−substrate complexes effectively lower the energetic barrier for reactions.20 We reasoned that strain-induced destabilization of the localized forms of 2,8:4,6-bis(ethano)semibullvalene (12loc, 12′loc) would result in 12 existing as the delocalized homoaromatic ground state species 12deloc.8 Intuitively, it is easy to see for 12loc,12′loc that, at the closed end of the semibullvalene nucleus, the bicyclo[2.1.0]pentane and the two spirocyclic (one of which is illustrated by the red bonds) moieties and, at the open end, the two anti-Bredt double bonds would induce extreme energy raising strain which would be ameliorated in 12deloc (Scheme 4). By a similar argument, we also predicted monoannelated 13 would possess an exceedingly small or nonexistent barrier to the Cope rearrangement (Scheme 5). In support of these predictions, we calculated that 12 and 13 should both be homoaromatic ground state species, 12deloc and 13deloc.21 In this article we present similar results for the corresponding 1,5-dimethylsemibullvalenes 12a and 13a. The

and Chamot speculated that trimethano bisannelation of the semibullvalene termini would inhibit the “breathing motion” of the Cope process and perhaps lead to a homoaromatic molecule 15deloc.25 We recently experimentally validated our prediction that strain, introduced through annelation of the semibullvalene nucleus, would result in a homoaromatic ground state. Using infrared spectroscopy, we proved that the semibullvalene bisanhydride 16 is homoaromatic in the gas-phase.25 In this article we present the results of our calculations detailing how additional straining of the semibullvalene nucleus can provide a path toward realization of ground state homoaromatic species.



RESULTS AND DISCUSSION In order to elevate this intuitive level of understanding to a more quantitative measure of the contribution of the strain induced upon annelation in directing the resulting annelated4137

DOI: 10.1021/acs.joc.7b00043 J. Org. Chem. 2017, 82, 4136−4147

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The Journal of Organic Chemistry semibullvalenes toward homoaromatic ground states, we designed a series of isodesmic reactions to estimate strain energies. These isodesmic reactions allow for the separation of the additional strain induced upon annelation from the inherent strain of the semibullvalene nucleus as investigated by Borden et al.17,18 In addition, the use of isodesmic reactions probes the more subtle broader molecular “strain” rather than just the release of strain upon the simple cleavage of a three-membered ring. More specifically, to explore the role of strain energy (SE) in lowering the activation barrier to the Cope rearrangement in annelated semibullvalenes, we focused on the magnitude of the SEs. At first sight, it may appear that the difference in strain energies between the localized and delocalized forms (ΔSE = SEdeloc − SEloc) would serve as a better indicator of the role of strain in these systems. However, ΔSE is independent of the isodesmic equation used and only reflects the difference in activation barriers between the strained system and its unstrained model (ΔSE = ABstrained − ABunstrained, AB = activation barrier) vide inf ra. Computational Methods. We and others have previously shown that a wide variety of Cope systems can be successfully modeled using B3LYP/6-31G* density functional theory.26 These studies justify our continued use of this method as our primary computational tool. Most structures reported in this study were fully optimized using the B3LYP/6-31G*, the B3PW91/6-31G*, and the HF/6-31G* methods as implemented in the Gaussian 09 suite of programs.27 All optimized geometries were confirmed to be minima (zero imaginary frequencies) or transition structures (one imaginary frequency) through their calculated energy second derivatives. Transition structures were further characterized by visualizing the normal mode associated with the imaginary frequency and by carrying out intrinsic reaction coordinate (IRC) calculations beginning with the optimized transition structure. B3LYP/6-31G* single point calculations were also performed on structures of fixed conformations from optimized HF/6-31G* geometries. We adopt the same conventions throughout this article for each isodesmic reaction: The localized and delocalized forms of each system are identified by appending a superscript loc or deloc to the compound number. All isodesmic equations are set up such that the “unstrained” Cope species is on the left of the equation and the strained material on the right. We define the strain energy (SE) such that a smaller value (more negative) indicates a less strained system. These conventions are illustrated in isodesmic reactions A and B and in SE eqs 1 and 2. cis-Divinylcyclopropane and Homotropilidene. We began our studies with the simplest strained Cope systems, cis-divinylcyclopropane (4) and homotropilidene (1) using the isodesmic reactions Aloc, Adeloc, Bloc, and Bdeloc and calculating the strain energy (SE) by the eqs 1loc, 1deloc, 2loc, and 2deloc. For reactions A, we initially located the chair- (C2h) and boat-like (C2v) conformations for the Cope TS (17del(Chair) and 17del(Boat)) and subsequently used these structures in IRC calculations to find the corresponding 1,5-hexadiene ground states 17loc(Chair) of C2 symmetry and 17loc(Boat) of C1 symmetry. We also found a lower energy ground state of Ci symmetry (17loc(Ci)). Although it is well-known that the Cope rearrangement of 4 goes through a boat-like TS,28,29 we wished to examine the difference in SE between the chair-like and boatlike pathways. We used eq 1loc (Scheme 7) to calculate the SE in going from each of 17loc(Chair) to 4loc(Chair), 17loc(Boat) to 4loc(Boat), 17loc(Ci) to 4loc(Chair), and 17loc(Ci) to

Scheme 7

4loc(Boat) and similarly eq 1deloc (Scheme 8) to calculate the corresponding SEs of 4deloc(Chair) and 4deloc(Boat). Obviously Scheme 8

there is no delocalized Ci geometry of 17 to serve as a reference. As can be seen from Table 2, the calculated strain energies hardly vary when the conformation of the localized 1,5-hexadiene reference (17) is changed from the chair or boat forms to the Ci conformer. Thus, for consistency in the comparison of conformationally mobile substrates throughout the remainder of this article, only the results obtained using the lowest energy conformer found will be presented. While it is well-known that the Cope rearrangement of 1,5-hexadiene proceeds preferentially through a chair conformation,30 the corresponding boat rearrangement is more appropriate for our purposes as it maps more closely with the bridgedhomotropilidenes. Conformational mobility is much more restricted in the homotropilidene system 1/5 than the corresponding cis-divinylcyclopropane system 4/17. The lowest energy conformation of 1,4-cycloheptadiene (5loc), which we used in our calculation of strain energies, is of C2 symmetry (axis shown in the planar representation).28,29,31 Its structure is more accurately represented in the perspective drawing in which the C2 axis passes through the center of the C6−C7 bond and the C3 atom (open circle partially obscured by the C6−C7 bond). Similarly, we used the Cs conformation of 4deloc(Boat) in calculating the SE of 1deloc. It is immediately obvious from the SEs in Table 2 that there is much greater release of strain in 4deloc and 1deloc than in the corresponding localized species and that this diminution in strain correlates with the calculated and observed Cope activation parameters. It is also important to note that the release of SE in the boat-like rearrangement of 4 is >20 kcal/mol that for the chairlike rearrangement and correlates directly with the significantly lower activation barriers for the boat-like path. We thus confined our estimate of the SE for homotropilidene (1) to eq 2 in which 4deloc(Boat) is the only delocalized conformation considered (Scheme 9). Zora similarly correlated decreasing ring strain in the 3-membered ring of cyclopropane (18) as one methylene group is successively replaced by NH, O, PH, and S with the increasing barrier for the corresponding heteroatom substituted Cope rearrangement of 4 and its hetetero-atom 4138

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Table 2. Calculated Strain Energies for cis-Divinyl Cyclopropane (4) and Homotropilidene (1) and the Enthalpies and Free Energies of Activation for Their Cope Rearrangementsa ΔEc = Edeloc − Eloc

strain energy (SE) kcal/mol strained Cope system (unstrained model)

computational method (strain energy equation)

4(Chair) (17(Chair))

B3LYP (1loc/1deloc) B3PW91 (1loc/1deloc) HF (1loc/1deloc) B3LYP//HF (1loc/1deloc) B3LYP (1loc/1deloc) B3PW91 (1loc/1deloc) HF (1loc/1deloc) B3LYP//HF (1loc/1deloc) B3LYP (1loc/1deloc) B3PW91 (1loc/1deloc) HF (1loc/1deloc) B3LYP//HF (1loc/1deloc) B3LYP (1loc/1deloc) B3PW91 (1loc/1deloc) HF (1loc/1deloc) B3LYP//HF (1loc/1deloc) B3LYP (2loc/2deloc) B3PW91 (2loc/2deloc) HF (2loc/2deloc) B3LYP//HF (2loc/2deloc)

4(Chair) (17loc(Ci))

4(Boat) (17(Boat))

4(Boat) (17loc(Ci))

1 (5)

Eloc zpe

Edeloc zpe

Hloc

Hdeloc

Gloc

Gdeloc

ΔH‡

ΔG‡

−2.63 −2.50 −1.11 −1.82b −2.02 −1.86 −0.50 −1.19b −3.86 −3.70 −2.23 −2.99b −3.55 −3.40

−8.20 −6.66 −6.60 −8.12b

−2.37 −2.24 −0.75

−7.93 −6.32 −6.37

−2.60 −2.44 −1.51

−8.28 −6.81 −6.60

27.02 26.32 48.81 27.65d 27.02 26.32 48.81 27.65d 15.96 15.83 35.55 16.33d 15.96 15.83

29.43 28.74 51.81

−1.85 −2.75b −6.65 −6.45 −5.39 −5.63b

−1.80 −1.65 −0.19 −28.73 −28.58 −29.95 −29.41b

−32.37 −31.67 −33.66 −33.13b

−3.58 −3.42 −1.92

−1.55 −1.38 −0.51 −28.70 −28.54 −29.90

−3.57 −3.44 −1.90

−3.35

−3.15

3.20 −1.60

3.03 −1.45

−6.40 −6.21 −5.10

−32.27 −31.54 −37.70

−6.56 −6.35 −5.08

−28.48 −28.33 −29.70

−31.47 −30.80 −32.82

35.55 16.33d 13.78 14.49 26.42 14.36d

29.43 28.74 51.81 18.40 18.39 38.08 18.40 18.39 38.08 15.21 15.95 32.34

a

Strain energies are reported as total electronic plus zero-point energy Ezpe (except for the single-point B3LYP//HF calculations), enthalpy H, and free energy G. bSE from total electronic energy without zero-point correction (E). cE = enthalpy (H) or Gibbs free energy (G) kcal/mol. dDifference in total electronic energy without zero-point correction ΔE = Edeloc − Eloc kcal/mol.

this study. These calculated SEs are in complete concurrence with Doering’s and Vogel’s intuitive assertions that these Cope rearrangements are accelerated by the relief of strain in the delocalized TSs. SemibullvalenesSide-Annelated. Side-annelation refers to annelation across the 2,8- and or 4,6-positions of the semibullvalene nucleus. Bisanhydride 16. The bisanhydride 16 is of particular interest as it is the first experimentally verified example of a neutral homoaromatic carbocycle.10,25,33,34 Naively, we expected that the simplest isodesmic reactions (eq 3loc/deloc, R = OH) would provide a meaningful estimate of SEloc and SEdeloc. As reported previously,9,25,35 at all correlated levels of theory investigated, except for the B3PW91/6-31G* method, we were unable to find a localized geometry, 16loc, for the bisanhydride. We optimized the structure of 16loc using both the HF/6-31G* and B3PW91/6-31G* methods and calculated SEs from the results of these computations as well as from single point B3LYP/6-31G* calculations on the optimized HF geometry (B3LYP/6-31G*//HF/6-31G*). At the B3PW91/6-31G* level 16loc and 16deloc are essentially degenerate whereas by B3LYP/ 6-31G*//HF/6-31G* 16deloc is calculated to be ∼2 kcal/mol more stable than 16loc. A problem with eq 3loc/deloc is that the use of the acyclic acetic anhydride does not account for any inherent strain in cyclic anhydrides.36 Of greater concern, forcing the disqualification of eq 3loc/deloc from further consideration, is the fact that there are multiple conformations of tetraacids 20aloc and 20adeloc (rotation about the semibullvalene−COR bond). These different conformations result in widely varying SEs dominated by dipolar interactions between neighboring carboxyl groups. Similar unsatisfactory and spurious results were obtained by applying eq 3loc/deloc to

Scheme 9

substituted analogues.28 He concluded that “Apparently, the ring strain has a predominant effect in determining the activation barriers for the rearrangements of divinylcyclopropane and divinylheterocyclopropanes, all of which involves the release of a three-membered ring’s strain.” Using isodesmic eqs 1 and 2, both 1 and 4 are calculated to be less strained than their “unstrained” models. This is not surprising as in 1 and 4 the cyclopropane moiety is significantly stabilized, compared with the parent cyclopropane (18) which serves as a part of the “unstrained” system, by conjugative interactions with the vinyl group.32 Clearly, the choice of isodesmic reactions strongly affects the calculated strain energies. However, internal comparisons of SEs from carefully chosen isodesmic reactions offer valid indicators of the degree of strain experienced by each system. The equality of ΔSE = ABstrained − ABunstrained is proved for homotropilidene (below SE eq 1deloc, Scheme 8) and it is immediately obvious that this equality holds for all systems in 4139

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The Journal of Organic Chemistry the tetrasesters (20bloc/deloc) and tetraaldehydes (20cloc/deloc) in the calculation of the corresponding SEs (Scheme 10).

Scheme 12

Scheme 10

annelations” (across the 1,5 positions) and “top/sideannelations”. (2,8) and 4,6-Ethanosemibullvalenes 13a and 2,8:4,6Bis(ethano)semibullvalenes 12a. From previous computational studies, we concluded that there is no localized form of 2,8-ethanosemibullvalene (13loc) while 4,6-ethanosemibullvalene (13′loc) has a localized ground state.21 With the major advances in computer power since our original work, for consistency and because of the well-known propensity for semibullvalenes lacking substituents at the 1,5-positions to be readily oxidized and easily polymerized,37 we focused our SE calculations presented herein on the synthetically more tractable and computationally larger 1,5-dimethyl derivatives of all of the systems studied. In concurrence with our previous calculations, in this study we were only able to locate 13aloc using HF calculations. As before for 13loc, at correlated levels of theory 13aloc collapsed to 13adeloc. We therefore conclude that 13a′loc (a minimum on the potential energy surface at all levels of calculation used) does not undergo Cope rearrangement. However, it is of particular interest to compare the SEs for 13a′loc and 13adeloc as a measure of the influence of strain in the homoaromatization (13adeloc) of 13a. We used a variety of isodesmic reactions to determine the SEs (Table 4, eqs 7, 8, and 9, Scheme 14) of 13a including for 13aloc at the HF and B3LYP//HF levels of theory. As is apparent from Table 4, all isodesmic equations and all computational methods reveal that 13adeloc is significantly less strained than 13a′loc and the homoaromatic 13adeloc is a ground state species of comparable energy to 13a′loc using the B3LYP/6-31G* method and the single point B3LYP//HF level. Interestingly, despite considerable efforts, we were unable to locate 13adeloc using B3PW91/ 6-31G*. Similarly to the ethanosemibullvalenes (13), we predicted that bis(ethano)semibullvalene 12 has a homoaromatic ground

In order to remove the issues of multiple conformations, strong dipolar interactions and the use of an acyclic anhydride, we next considered the isodesmic reactions illustrated in eq 4loc/deloc for the calculation of SEs (Scheme 11). These reactions are not only balanced (see color coding in isodesmic reaction Cloc for correspondences),36 but also remove the potential for influencing the SEs through dipolar interactions (Scheme 12). The less well balanced eqs 5loc/deloc and 6loc/deloc were also considered (Schemes 12 and 13). It should be noted that the SEs, as defined, measure the additional SE as a result of the perturbation of the semibullvalene nucleus by, for example, annelation, and do not address the inherent strain of this nucleus. The results presented in Table 3 clearly demonstrate, no matter which SE equation is used, that there is a significantly greater relief of strain (more negative SE) in 16deloc compared to that for 16loc. Experimentally, 16 is found to be a rapidly equilibrating Cope system in the condensed-phases and to have a homoaromatic ground state (16deloc) in the gas-phase.9,25 This relief of strain in 16deloc serves to eliminate the barrier to its Cope rearrangement (cf. parent semibullvalene 2 for which experimentally ΔG‡ (130 K) = 5.5 kcal/mol) and to ensure its homoaromaticity in the gas-phase. To aid in the identification of new homoaromatic targets and to confirm previously postulated targets, we next considered alternative “side-annelations” (across the 2,8 and/or 4,6 positions) of the semibullvalene nucleus in addition to “topScheme 11

4140

DOI: 10.1021/acs.joc.7b00043 J. Org. Chem. 2017, 82, 4136−4147

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The Journal of Organic Chemistry Scheme 13

Table 3. Calculated Strain Energies for the Semibullvalene Bisanhydride 16 and the Enthalpies and Free Energies of Activation for Its Cope Rearrangementsa ΔEc = Edeloc − Eloc loc

strain energy (SE) kcal/mol strained Cope system (unstrained Model) 16 16 16 16 16 16 16 16 16

(23) (23) (28) (23) (23) (28) (23) (23) (28)

computational method (strain energy equation)

Eloc zpe

Edeloc zpe

Hloc

Hdeloc

Gloc

Gdeloc

ΔH‡

ΔG‡

B3PW91 (4) B3PW91 (5) B3PW91 (6) HF (4) HF (5) HF (6) B3LYP//HF (4) B3LYP//HF (5) B3LYP//HF (6)

0.80 −2.19 −8.19 6.84 3.90 1.29 1.68b −0.55b −5.57b

−5.59 −8.58 −13.21 −6.34 −9.28 −6.78 −6.34b −8.57b −12.07b

1.08 −1.71 −6.77 7.07 4.34 2.65

−5.19 −7.98 −11.50 −6.49 −9.23 −5.45

2.79 −0.72 −4.22 8.78 5.35 5.42

−3.29 −6.79 −9.66 −2.81 −6.23 −2.70

−0.03 −0.03 −0.03 7.01 7.01 7.01 −2.03d −2.03d −2.03d

−0.08 −0.08 −0.08 7.53 7.53 7.53

a Strain energies are reported as total electronic plus zero-point energy Ezpe (except for the single-point B3LYP//HF calculations), enthalpy H, and free energy G. bSE from total electronic energy without zero-point correction (E). cE = enthalpy (H) or Gibbs free energy (G) kcal/mol. dDifference in total electronic energy without zero-point correction ΔE = Edeloc − Eloc kcal/mol.

Table 4. Calculated Strain Energies for the Ethanosemibullvalene 13a and the Enthalpies and Free Energies of Activation for Its Cope Rearrangementsa ΔEb=Elocdeloc−E-

strain energy (SE) kcal/mol strained Cope system (unstrained model) 13a′loc/13adeloc 13a′loc/13adeloc 13a′loc/13adeloc 13a′loc/13adeloc 13a′loc/13adeloc 13a′loc/13adeloc 13a′loc/13adeloc 13a′loc/13adeloc 13a′loc/13adeloc

(30a) (30a) (30a) (30b) (30b) (30b) (30b) (30b) (30b)

computational method (strain energy equation)

Eloc zpe

Edeloc zpe

Hloc

Hdeloc

Gloc

Gdeloc

ΔH‡

ΔG‡

B3LYP(7) B3LYP(8) B3LYP(9) HF (7) HF (8) HF (9) B3LYP//HF (7) B3LYP//HF (8) B3LYP//HF (9)

16.51 −3.80 14.34 19.93 −1.47 18.23 24.14 −5.26 14.57

9.16 −11.12 6.99 8.71 −12.70 7.01 12.21 −12.80 7.03

17.57 −3.98 14.28 20.68 −1.39 18.07

10.21 −11.05 7.22 9.37 −12.70 6.76

9.58 −3.98 14.81 13.00 −2.32 19.67

2.23 −11.33 7.46 2.22 −13.10 8.89

1.07 1.07 1.07 9.23 9.23 9.23 1.20 1.20 1.20

0.33 0.33 0.33 9.17 9.17 9.17

a Strain energies are reported as total electronic plus zero-point energy Ezpe (except for the single-point B3LYP//HF calculations), enthalpy H, and free energy G. bE = enthalpy (H) or Gibbs free energy (G) kcal/mol.

state (12deloc) and that, with correlated methods (except for MNDO 2 × 2 CI), the localized forms (12loc) are not at stationary points.21 In this study, using correlated methods we were also unable to find stationary points corresponding with the 1,5-dimethyl derivative (12aloc, Scheme 15). Thus, we only report SEs for the localized species using HF and single point B3LYP//HF computations. Comparing the data in Tables 4 and 5, it is apparent that, in accord with intuition, the bisannelated semibullvalenes 12a are

more strained than their monoannelated counterparts 13a. In fact, where direct comparison is most meaningful (the same computational method and equivalent SE eqs 7 and 10), the bisannelated system is about twice as strained as the monoannelated. This increased strain in 12a over 13a correlates with the lack, except at the HF level, of a localized form of 12a and our assertion that strain is the causative factor in the homoaromatization of the semibullvalene nucleus of 12a. Again, the choice of isodesmic reaction has a profound 4141

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Scheme 15

Table 5. Calculated Strain Energies for the Bisethanosemibullvalene 12a and the Enthalpies and Free Energies of Activation for Its Cope Rearrangementsa ΔEc=Edeloc−Eloc loc

strain energy (SE) kcal/mol strained Cope system (unstrained model) 12a 12a 12a 12a 12a 12a 12a 12a 12a 12a 12a 12a

(23) (23) (23) (23) (23) (23) (23) (23) (23) (23) (23) (23)

computational method (strain energy equation) B3LYP (10) B3LYP (11) B3LYP (12) B3PW91 (10) B3PW91 (11) B3PW91 (12) HF (10) HF (11) HF (12) B3LYP//HF (10) B3LYP//HF (11) B3LYP//HF (12)

Eloc zpe

Edeloc zpe

35.86 32.46 12.71 35.51 25.16 5.34

19.58 15.23 −2.84 16.01 13.90 −5.13 17.12 13.72 −6.00 24.69 14.35 −5.47

Hloc

Hdeloc

37.59 32.37 12.91

20.80 14.82 −3.40 17.68 13.96 −4.92 18.46 13.24 −6.23

Gloc

Gdeloc

21.65 34.99 12.96

6.60 17.07 −1.66 2.56 15.15 −5.24 4.13 17.46 −4.56

ΔH‡

ΔG‡

1.45 1.45 1.45 −4.82 −4.82 −4.82

2.00 2.00 2.00

a

Strain energies are reported as total electronic plus zero-point energy Ezpe (except for the single-point B3LYP//HF calculations), enthalpy H, and free energy G. bSE from total electronic energy without zero-point correction (E). cE = enthalpy (H) or Gibbs free energy (G) kcal/mol. dDifference in total electronic energy without zero-point correction ΔE = Edeloc − Eloc kcal/mol.

2,8:4,6-Bis(trismethano)semibullvalene 15a. Increasing the annelating ring size from the bis(ethano)-12a to the bis(trismethano)-semibullvalene 15a (Scheme 16) results in dramatic changes. Localized and delocalized minima for 15a were found using all three of our standard computational methods. In each case the delocalized form is less strained than the localized form, but the release in SE for 15adeloc is small in comparison with the corresponding releases in SEs for 12adeloc (Table 6). Using the B3LYP, B3PW91, and B3LYP//HF methods 15aloc/15adeloc are essentially degenerate, while at the

influence on the magnitude (and sign) of the SEs. The balanced isodesmic reaction (eq 12) shows that the delocalized homoaromatic 12adeloc is less strained than its constituents (23deloc, 31, and 32) while the other two isodesmics put 12adeloc to be more strained than its corresponding constituents (19 or 32). This, of course, is a consequence of including the strained cyclobutane as a reference in the balanced equation. No matter which isodesmic reaction is used, 12adeloc is calculated to be considerably less strained than 12loc. 4142

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The Journal of Organic Chemistry Scheme 16

Table 6. Calculated Strain Energies for the Bis(trismethano)semibullvalene 15a and the Enthalpies and Free Energies of Activation for Its Cope Rearrangementsa ΔEc = Edeloc − Eloc loc

strain energy (SE) kcal/mol strained Cope system (unstrained model) 15a 15a 15a 15a

(23) (23) (23) (23)

computational method (strain energy equation)

Eloc zpe

Edeloc zpe

Hloc

Hdeloc

Gloc

Gdeloc

ΔH‡

ΔG‡

B3LYP (13) B3PW91 (13) HF (13) B3LYP//HF (13)

0.89 0.49 4.74 1.96b

−3.60 −5.12 −6.39 −4.83b

1.25 0.82 5.02

−3.98 −5.04 −6.53

0.62 0.24 5.31

−2.52 −4.59 −4.42

−0.16 0.38 9.02 −0.79d

0.72 1.15 9.79

a

Strain energies are reported as total electronic plus zero-point energy Ezpe (except for the single-point B3LYP//HF calculations), enthalpy H, and free energy G. bSE from total electronic energy without zero-point correction (E). cE = enthalpy (H) or Gibbs free energy (G) kcal/mol. dDifference in total electronic energy without zero-point correction ΔE = Edeloc − Eloc kcal/mol.

Table 7. Calculated Strain Energies for the Bisether 35 and the Enthalpies and Free Energies of Activation for Its Cope Rearrangementsa ΔEc = Edeloc − Eloc loc

strain energy (SE) kcal/mol strained Cope system (unstrained Model) 35 35 35 35

(23) (23) (23) (23)

computational method (strain energy equation)

Eloc zpe

Edeloc zpe

Hloc

Hdeloc

Gloc

Gdeloc

ΔH‡

ΔG‡

B3LYP (14) B3PW91 (14) HF (14) B3LYP//HF (14)

−0.23 −0.69 3.31 0.97b

−4.95 −6.54 −9.43 −5.64b

−0.05 −0.59 3.47

−4.99 −6.68 −9.64

0.85 0.53 4.04

−3.30 −4.59 −7.43

0.13 0.15 7.46 −0.61d

−0.29 0.86 8.06

a Strain energies are reported as total electronic plus zero-point energy Ezpe (except for the single-point B3LYP//HF calculations), enthalpy H, and free energy G. bSE from total electronic energy without zero-point correction (E). cE = enthalpy (H) or Gibbs free energy (G) kcal/mol. dDifference in total electronic energy without zero-point correction ΔE = Edeloc − Eloc kcal/mol.

Scheme 17

HF level, the localized form is appreciable more stable than the

to be homoaromatic in the gas phase, support the notion that

delocalized. Similar comparisons between 15a and the

15a is unlikely to exist as a homoaromatic species. 2,8:4,6-Bis(ether) 35. The bis(ether) 35 offers an interesting

bisanhydride 16, which we have experimentally demonstrated

bridge between bisanhydride 16 and the bis(trismethano) 15a. 4143

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bisanhydride 16 is a ground state homoaromatic in the gasphase.25 We speculate that top- and side-annelations of semibullvalene are likely to be synergistic and that combining these annelations in a single molecule will provide the best chance of achieving a homoaromatic ground state in the condensed phase. The synthesis of 2,8:4,6-bis(ethano)semibullvalenes is a daunting task and consequently we have focused our efforts on top-annelation of the bisanhydride 16. 1,5-(Bismethano)semibullvalene bisanhydride 46, 1,5(Trismethano)semibullvalene bisanhydride 47, and 1,5(Tetramethano)semibullvalene bisanhydride 42. For consistency, we used the balanced isodesmic reactions 27/28/29 with the hexamethyl semibullvalene 23 as the unstrained reference (Scheme 20). It is noteworthy that for the bismethano- and trismethano-bisanhydrides 46 and 47 no localized form was found with either the B3LYP or B3PW91 methods while a localized structure was located for the tetramethano-bisanhydride 42 at the B3PW91 level. At the HF level, the localized forms are more stable than the delocalized forms of 46, 47, and 42 while single point B3LYP//HF calculations show the delocalized forms are favored with the bismethano 46 showing the greatest relative stabilization compared to the localized form (Table 9). All measures of SE for 46, 47, and 42 show the same trends. In every case the SE of the delocalized forms is much less than that of the localized forms and, with increasing size of the top annelating ring, the SE decreases (Table 9). Considering all of these factors together, we predict that 46 and 47 are most likely to be homoaromatic ground state species and, in agreement with experiment,44 42 is predicted not to be homoaromatic in the condensed phase.

The calculated SEs and differences in enthalpy and free energy are almost the same for 15a (Table 6) and 35 (Table 7) suggesting that, like 15a, 35 will not have a homoaromatic ground state (Scheme 17). SemibullvalenesTop-Annelated. Top-annelation refers to annelation across the 1,5-positions of the semibullvalene nucleus. Dannenberg et al. predicted, from semiempirical calculations, that the cyclopropyl annelated 38 should be homoaromatic.38 More recent, higher level, calculations by Brown et al. led them to predict that 38 is not homoaromatic despite a C2v geometry that is lower in energy than the localized Cs structure and suggest that the C2v form is favored by the extreme level of strain in the Cs species.39 They concluded that the interallylic interaction in C2v 38 is so small that it would exist as a triplet diradical and caution that semibullvalenes with a C2v geometry are not necessarily homoaromatic. Of the 1,5annelated semibullvalenes, only those with a 5- to 8-membered annelation have been prepared.40,41 Quast and Jackman et al. experimentally verified that medium ring 1,5-annelation significantly lowers the activation barrier for the Cope rearrangement. In fact, they comment that “the tetramethylene bridge as in [40] and, in particular, the trimethylene bridge as in [39] lower the [Cope activation] barrier more than any of the substituents on the allylic moiety that have been investigated so far!”40 They found that the shorter methylene bridge (39) resulted in the lower barrier than with the longer bridge (40). Grohmann prepared the top-annelated tetraesters 41, and again the more strained 5- and 6-membered ring annelated species show a significantly decreased activation barrier to the Cope rearrangement, but are not homoaromatic.41 We prepared the 1,5-tetramethano-bisanhydrides 42/ 42a, which undergo such rapid Cope rearrangement that activation parameters could not be determined by 500 MHz NMR spectroscopy. Using a modified Saunders’ isotopic perturbation procedure with 42a,42,43 we determined that 42a and hence 42 are not homoaromatic in the condensed phase (Scheme 18).44



CONCLUSIONS Despite its long history, aromaticity remains a controversial area of study.45 Even the classification of a compound as aromatic can lead to heated debate, while any attempt at constructing a scale of aromaticity is fraught with difficulties and disbelief.46 These issues are probably more pronounced when discussing homoaromaticity.7,8 However, for the bridged homotropilidenes, it is widely accepted that the more symmetrical “delocalized” forms are homoaromatic and, as a natural extension, the difference in energy between the localized and delocalized (homoaromatic) semibullvalenes can be related to the degree of homoaromaticity. In this article, several highly strained semibullvalenes are predicted to be neutral homoaromatic ground state species. Some of these delocalized semibullvalenes are calculated to coexist with the corresponding localized forms while others are the only stationary points located using correlated methods. As we were unable to locate localized forms, using correlated methods, for most of the semibullvalenes we predict to be homoaromatic, we used the difference in single point energy (B3LYP/6-31G*//HF/6-31G*) between the delocalized and localized forms (ΔE = Edeloc − Eloc) as a measure of their homoaromaticity. Considering the scatter plot of strain energy (SE) against ΔE, Figure 1, derived from all isodesmic reactions using hexamethyl semibullvalene (23) as the unstrained reference compound, it is immediately apparent that there is a strong correlation between SE and ΔE and hence between SE and the degree of homoaromaticity. We have already noted, as pointed out by Herndon et al.36 the impact of the exact nature of the isodesmic reaction on the parameter this reaction is designed to probe. Despite limiting the unstrained reference to

Scheme 18

Top-Annelated Semibullvalenes: 1,5-Bismethanosemibullvalene 43, 1,5-Trismethanosemibullvalene 44, and 1,5Tetramethanosemibullvalene 45. Top annelation certainly decreases the difference in energy between the localized and delocalized forms compared with the parent semibullvalene nucleus, but 43loc, 44loc, and 45loc (Scheme 19) are all predicted to be lower in energy than their corresponding delocalized species (Table 8). Their SEs vary according to expectations with 4-ring annelation exhibiting the greatest degree of strain and the largest release in SE in the delocalized forms (Table 8). SemibullvalenesTop- and Side-Annelated. Our calculations indicate that side-annelation is more effective in reducing the Cope activation barriers in semibullvalene nuclei than top-annelation and we have shown experimentally that 4144

DOI: 10.1021/acs.joc.7b00043 J. Org. Chem. 2017, 82, 4136−4147

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The Journal of Organic Chemistry Scheme 19

Table 8. Calculated Strain Energies for the Top-Annelated Semibullvalenes 43, 44, and 45 and the Enthalpies and Free Energies of Activation for Their Cope Rearrangementsa ΔEc = Edeloc − Eloc loc

strain energy (SE) kcal/mol strained Cope system (unstrained Model) 43 44 45 43 44 45 43 44 45 43 44 45

(23) (23) (23) (23) (23) (23) (23) (23) (23) (23) (23) (23

computational method (strain energy equation)

Eloc zpe

Edeloc zpe

Hloc

Hdeloc

Gloc

Gdeloc

ΔH‡

ΔG‡

B3LYP (15) B3LYP (16) B3LYP (17) B3PW91 (15) B3PW91 (16) B3PW91 (17) HF (15) HF (16) HF (17) B3LYP//HF (15) B3LYP//HF (16) B3LYP//HF (17)

5.98 −2.15 2.66 5.41 −2.07 2.75 6.58 −2.06 3.40 5.62b −1.77b 2.99b

2.74 −3.46 3.09 2.52 −3.57 2.92 4.31 −3.50 3.50 2.38b −3.17b 3.76b

6.27 −1.98 3.03 6.06 −1.90 3.11 7.22 −1.97 3.78

2.82 −3.57 3.52 3.56 −2.96 3.34 4.93 −3.52 3.84

4.81 −1.82 1.77 3.56 −1.78 1.91 4.74 −0.69 2.55

2.16 −2.70 1.71 0.14 −4.37 1.99 2.64 −1.94 3.01

1.63 3.49 5.56 3.74 5.18 6.47 18.29 19.03 20.63 2.76d 4.59d 6.76d

1.20 2.98 3.79 2.56 3.39 6.07 17.43 18.28 19.98

a

Strain energies are reported as total electronic plus zero-point energy Ezpe (except for the single-point B3LYP//HF calculations), enthalpy H, and free energy G. bSE from total electronic energy without zero-point correction (E). cE = enthalpy (H) or Gibbs free energy (G) kcal/mol. dDifference in total electronic energy without zero-point correction ΔE = Edeloc − Eloc kcal/mol.

Scheme 20

4145

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Table 9. Calculated Strain Energies for the Top-Annelated Semibullvalene Bisanhydrides 46, 47, and 42 the Enthalpies and Free Energies of Activation for Their Cope Rearrangementsa ΔEc = Edeloc − Eloc

strain energy (SE) kcal/mol strained Cope system (unstrained model) 46 47 42 46 47 42 46 47 42 46 47 42

(23) (23) (23) (23) (23) (23) (23) (23) (23) (23) (23) (23)

computational method (SE e) B3LYP(27) B3LYP(28) B3LYP(29) B3PW91 (27) B3PW91 (28) B3PW91(29) HF (27) HF (28) HF(29) B3LYP//HF (27) B3LYP//HF (28) B3LYP//HF(29)

Eloc zpe

Edeloc zpe

3.28 16.63 5.50 9.28 10.02b 0.73b 4.42b

1.33 −7.54 −3.00 1.31 −7.34 −3.07 2.31 −8.18 −3.56 −0.01b −8.14b −3.37b

loc

H

4.00 17.41 5.78 9.97

deloc

H

1.37 −7.55 −2.63 2.18 −6.86 −2.17 2.71 −8.27 −3.23

G

loc

4.21 16.83 8.85 10.21

G

deloc

3.22 −4.56 −1.17 2.01 −4.94 −1.92 3.67 −4.06 −1.47

ΔH‡

ΔG‡

0.07 5.88 6.52 7.38 −4.04d −2.87d −1.79d

−0.15 6.37 6.62 7.85

a Strain energies are reported as total electronic plus zero-point energy Ezpe (except for the single-point B3LYP//HF calculations), enthalpy H, and free energy G. bSE from total electronic energy without zero-point correction (E). cE = enthalpy (H) or Gibbs free energy (G) kcal/mol. dDifference in total electronic energy without zero-point correction ΔE = Edeloc − Eloc kcal/mol.



ASSOCIATED CONTENT

* Supporting Information S

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b00043. Cartesian coordinates and energies for key compounds calculated (PDF)



AUTHOR INFORMATION

Corresponding Author

*[email protected] ORCID

Richard Vaughan Williams: 0000-0001-5935-3618 Present Address

Figure 1. Plot of strain energy (SE, kcal/mol) against the difference in the B3LYP/6-31G*//HF/6-31G* energies of the localized and delocalized (homoaromatic) forms (ΔE, kcal/mol) of each semibullvalene using hexamethyl semibullvalene 23 as the unstrained reference.



Sabbatical visitor from Department of Chemistry, Faculty of Science, King Khalid University, Abha 61413, P.O. Box 9004, Saudi Arabia. Notes

The authors declare no competing financial interest.

■ ■

ACKNOWLEDGMENTS R.V.W. gratefully acknowledges the National Science Foundation (CHE-0714761) for support of this work.

semibullvalene 23 in Figure 1, there are some obvious outliers in this plot. The points marked 1, 2, and 3 all report the SE (from 3 different isodesmic reactions) and ΔE for the bis(ethano)semibullvalene 12a. However, the outlying points 1 and 2 are the product of unbalanced isodesmic reactions, which do not incorporate the additional strain of a fourmembered ring. Not only does this plot support the notion that strain is a causative factor in the homoaromatization of annelated semibullvalenes, but it also reinforces the need for careful construction of isodesmic reactions. Straining the semibullvalene nucleus, as described in this article, always results in a greater release of strain in the delocalized (as indicated by a smaller, more negative, strain energy) than in the corresponding localized forms. Strain, through top annelation of the semibullvalene nucleus, can result in decreased homoaromaticity, a tendency to increased interallylic separation and ultimately triplet ground states.39 Top and side annelation work synergistically toward favoring ground state homoaromatics.

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DOI: 10.1021/acs.joc.7b00043 J. Org. Chem. 2017, 82, 4136−4147