Oxepin calculations

Three decades ago the preparation of oxepin represented a considerable synthetic challenge. The theoretical impetus for these efforts was the consideration that oxepin can be regarded as an analog of cyclooctatetraene in the same sense that furan is an analog of benzene. The possibility of such an electronic relationship was supported by molecular orbital calculations suggesting that oxepin might possess a certain amount of aromatic character, despite the fact that it appears to violate the [4n + 2] requirement for aromaticity. By analogy with the closely related cycloheptatriene/norcaradiene system, it was also postulated that oxepin represents a valence tautomer of benzene oxide. Other isomers of oxepin are 7-oxanorbornadiene and 3-oxaquadricyclane.1 Both have been shown to isomerize to oxepin and benzene oxide, respectively (see Section 1.1.2.1.). 

Accurate molecular dimensions on oxepin have not been obtained experimentally but are available from a range of calculations (Table 2). 

The spontaneous oxepin-benzene oxide isomerization proceeds in accordance with the Woodward-Hoffmann rules of orbital symmetry control and may thus be classified as an allowed thermal disrotatory electrocyclic reaction. A considerable amount of structural information about both oxepin and benzene oxide has been obtained from theoretical calculations using ab initio SCF and semiempirical (MINDO/3) MO calculations (80JA1255). Thus the oxepin ring was predicted to be either a flattened boat structure (MINDO/3) or a planar ring (SCF), indicative of a very low barrier to interconversion between boat conformations. Both methods of calculation indicated that the benzene oxide tautomer... 

The dipole moments of oxepin and benzene oxide have been calculated to be in the range 0.76-1.36 D and >1.5 D respectively using the ab initio SCF and MINDO/3 methods (80JA1255). The lower calculated dipole moment would be in accord with experimental observations where the equilibrium was found to favor oxepin (7) in less polar solvents. Coordination between the oxirane oxygen atom and polar solvent molecules would also strengthen the C—C bond of the epoxide and thus lead to a preference for the benzene oxide isomer <72AG(E)825). Thus the proportion of oxepin (7) was found by UV spectral analysis to be higher in isooctane solvent (70%) than in water-methanol (10%). 

The nature and position of substitution has a profound influence upon the oxepin-arene oxide equilibrium position. The effect of substituents on the relative energies of each valence tautomer has been calculated (80JA1255) and these theoretical results are in accord with the limited experimental data which are available. In general terms, oxepins substituted at the 3-position are less favored than the corresponding arene oxides, while the reverse obtained for 2- and 4-substituted oxepins. This substituent effect has been rationalized in terms of a preference for the maximum number of alternative resonance contributors. The influence of both 7r donating and v withdrawing substituents oh the oxepin contribution is summarized in Scheme 2. This latter effect may be considered as an electronic substituent effect. 

Similarly, the fusion of an aromatic ring to the oxepin-benzene oxide system was found to drive the equilibrium toward extremes in either direction. The calculated resonance energies for oxepins (26), (27) and (28) were 4.81, 78.46 and 81.72 kJ mol-1 respectively (70T4269). These calculated values concur with experimental observations since oxepins (27) and (28) have been synthesized and are relatively stable compounds. The formation of 2-benzoxepin (26) from naphthalene 1,2-oxide would involve a considerable loss in resonance energy to the system and has not been detected spectroscopically (67AG(E)385). 

Using both semi-empirical and ab initio calculations the study of oxepin (6), benzene oxide (7), and their equilibrium (Scheme 2) has been conducted. The fully optimized geometry (90MI902-01) agrees with that experimentally found for several substituted oxepines. The carbon skeleton of benzene oxide is practically planar while the angle between the epoxide ring and the adjacent plane is ca. 106°. The oxepin molecule is boat-shaped with a fold angles between C2—C7 and C3—C6 of ca. 137 and 159°, respectively. 

HMO calculations, based on localized polyenes instead of isolated alkenes, can account for the heats of atomization of furan (41.64 observed, 41.69 eV) and of dibenzofuran (109.09 observed, 108.92 eV). For resonance energies (quoted as resonance energy per electron, REPE) they give furan, 0.007 oxepin, -0.006 benzo[6]furan, 0.036 benzo[c]furan, 0.002 and dibenzofuran, 0.047 /3 (72T3657). That furan emerges as hardly more aromatic than a diene while pyrrole (REPE 0.039/3) is clearly aromatic is in line with other results, including those from MINDO/3 and topological methods (see Section... 

Naphthalene 1,2-oxide (136), a non-K-region epoxide, shows low thermal stability. Anthracene 1,2-oxide, on the other hand, is stable at ambient temperatures for several weeks. Preparation of (+ )-(lR,2S)-anthracene 1,2-oxide (137), using the above method, constitutes the first example of preparation of an optically pure arene oxide. However, the non-K-region oxides of phenanthrene, namely, its 1,2- and 3,4-oxides (47 and 48), obtained from chiral precursors, racemize fast.66 Perturbational molecular orbital calculations indicate that epoxide-oxepin valence tautomerism is possible. However, the oxepin could not be detected by NMR. 

Substitution of methyl groups on the oxirane ring tilts the stability of the tautomers in favor of oxepin. Thus 1-methylbenzene oxide (154) exists as 2-methyloxepin (155), in rapid equilibrium with the benzene oxide tautomer 154.74 The AH has been calculated as 0.4 0.02 kcal/mol, i.e., 1.3 kcal/mol... 

Valence tautomers, benzene oxide 1 and oxepine 2 (Equation 1), as well as relative tautomeric systems, benzene sulfide-thiepine and o-xylene-2,7-dimethyloxepine, have been studied by a post-Hartree-Fock (HF) ab initio QCISD(r)/6-31G //MP2/6-31G method. In particular, the enthalpy calculated for a benzene oxide-oxepine system is 0.59 kj moF1 <1997PCA3371>. The calculated molecular orbital (MO) energies are in linear relationship to those from the photoelectron (PE) spectra <1996JCF1447>. Barrier to tautomerization for a benzene oxide-oxepine system is 29.4 kj mol-1. Protonation stabilizes the oxide form versus the oxepine <1997PCA3371>. 

Thermodynamic parameters for the benzene oxide-oxepine system are calculated at MP4(SDQ)/6-31+G //HF/ 6-31G level of theory. The effect of solvent polarity on the above equilibrium is studied using the isodensity polarized continuum method. Low polar solvents favor the oxepine formation, whereas medium to high polar solvents lead to benzene oxide formation. The transition state for the tautomerization is fully characterized and the activation energies for the forward and reverse reaction are estimated to be ca. 9.5 and 11.0 kcal mol-1, respectively. The solvent polarity exerts a reasonable effect decreasing the activation energies up to 4 kcal mol-1 <2001MI471>. 

The mechanism of the atroposelective ring opening of a lactone-bridged biaryl, dinaphtho[2,l-t l, 2 -< ]oxepin-3(5//)-one, with a chiral oxazaborolidine-BH3 complex (Scheme 2) was studied using semi-empirical AMI calculations <2000JOC2517>. 

Additional evidence for the rapid equilibration in the benzene oxide-oxepin system la-lb has accrued from a range of molecular orbital (MO) calculations. ... 

Preferred geometry of the benzene oxide-oxepin system can be predicted by molecular orbital methods. Thus benzene oxide la is predicted to be markedly non-planar (with the epoxide ring at an angle of 73° to the benzene ring), while the oxepin lb has been predicted to prefer a shallow boat structure (MINDO/3) or a planar structure ab initio) As previously mentioned, the proportion of each tautomer present at equilibrium is both temperature and solvent-dependent. Molecular orbital calculations have been used to rationalize the solvent effects, both in terms of the more polar character of the arene oxide that is favored in polar solvents and the strengthening of the oxirane C-C bond upon coordination of the oxygen atom lone pair in polar solvents. Thus values in the range 1.5-2.0 D and 0.76-1.36 D for the dipole moments of arene oxide la and oxepin lb have been calculated. 

A further factor that has a marked influence upon the arene oxide-oxepin distribution is the effect of substituents. With the numbering system shown below, arene oxides, monosubstituted arene 1,2-, or 3,4-, and 1,2 disubstituted 1,2-oxides prefer their oxepin forms whereas arene 2,3-oxides prefer their oxide tautomers. These observations concur with MINDO/3 calculations and may be rationalized in terms of the maximum number of low-energy valence-bond structures for tt-electron-donating or withdrawing substituents (Figure 1). 

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