Valence isomerization of cyclohepta-1,3,5-triene and its heteroelement analogues

The valence isomerization of the all-carbon and heteroelement analogues of cyclohepta-1,3,5-triene into the corresponding bicyclo[4.1.0]hepta-2,4-dienes is reviewed to show the impact of the heteroatom on the stability of both valence isomers. The focus is on the parent systems and their synthetic applications.

Reviewing the influence of the heteroatom on the cycloheptatriene-norcaradiene valence isomerization necessitates a brief overview of the parent all-carbon system. This section is followed by one in which experimental data on the oxepine, thiepine, 1H-azepine, and 1H-phosphepine valence isomerizations are compared with those obtained by theoretical calculations. Computational methods have the advantage that they

Review Cycloheptatriene valence isomerization
Cyclohepta-1,3,5-triene (1), first isolated in 1883 [10], has a boat-shaped conformation as determined by electron diffraction [11] and microwave studies of the parent [12] and by an X-ray structure analysis of the derivative thujic acid [13,14]. These methods gave inconsistent α and β tilt angles (see Scheme 2 for a description of the bow (α) and stern (β) tilt angles) with those determined by electron diffraction standing out. Theoretical calculations at the B3LYP/6-311+G(d,p) level gave α and β angles of 52.9° and 25.4°, respectively [15][16][17], which are in reasonable harmony with those of the microwave and X-ray studies. Low temperature 1 H NMR measurements showed that the slightly homoaromatic boat conformation is prone to undergo a degenerate ring flip via an antiaromatic C 2v transition with a free energy barrier of 5.7 kcal·mol −1 in CBrF 3 [18] and 6.3 kcal·mol −1 in CF 2 Cl 2 [19][20][21].

Valence isomerization of heteropines
Determining the conformations of the heteropines has been more of a challenge. Only the parent oxepine (3) is isolable at room temperature. NMR spectroscopy indicated a boat-shape structure with alternating C=C bonds for 3 [39,40], which was supported by single-crystal X-ray structure analyses of simple derivatives [41]. Table 1 also summarizes the relative energies obtained by high-level theoretical calculations for the parent heteropines and the corresponding bicyclic norcaradienes, and the barriers for their interconversion and ring inversion.
Although the boat form prevails for the monocyclic heteropines 1, 3 and 5, Cremer et al. showed that this represents an incomplete picture [43,44]. In fact, they are "perturbed" boats with at least 22% chair character, leading to an almost similar boat   a Gibbs free energies for the experimental data (first two entries) and enthalpies for the computational data. b Equilibrium from CHT to NCD. c Equilibrium from NCD to CHT. puckering for all. From the racemization of substituted benzene oxides (Scheme 2), the oxepine ring inversion barrier was estimated at 6.5 kcal·mol −1 at 135 K [45,46], which is similar to the 3.5 kcal·mol −1 calculated for the parent oxepine (3) at the QCISD(T)/6-31G(d) level [40]. The calculated barrier of 8.3 kcal·mol −1 for thiepine (5) is nearly twice as large, possibly due to the higher antiaromatic destabilization of the flattened thiepine ring [40], but the interconversion of the boat forms of azepine and phosphepine are about equally favourable, requiring 3.0 [41] and 5.2 kcal·mol −1 [7,47], respectively.

Thiepine -benzene sulfide
The parent thiepine (5) is 7.0 kcal·mol −1 less stable than benzene sulfide (6). This energy difference is much larger than for the oxygen homologues, because three-membered rings accommodate sulfur better than oxygen [40]. Nonetheless, bicyclic 6 has never been isolated, probably due to the low activation barrier for sulfur extrusion [40,48,70], which occurs through a sequence of low-energy processes involving several sulfur-containing intermediates [71,72].
Also for the phosphepine system [108], benzannulation leads to interesting targets. Namely, the thermal lability of the transition-metal-complexed 3H-benzophosphepine 33 was explored by Lammertsma et al. for the synthesis of a variety of organophosphorus compounds by means of [1 + 2] cycloadditions of the in situ generated singlet phosphinidene 35 with olefins or acetylenes (Scheme 7) [5][6][7][8][9]. This approach has even lead to the detection of the transient phosphinidene species by employing electrospray ionization tandem mass spectrometry (ESIMS/MS); its gas-phase reactivity perfectly matches the well-established solution-phase chemistry [109]. Using these phosphinidenes [110,111] led to the synthesis of unique P-ligands for catalysis [112,113] as well as to attractive building blocks for the creation of P-functionalized polymers [114,115].

Conclusion
The valence isomerization of cyclohepta-1,3,5-triene into the parent norcaradiene, and of their corresponding heteroelement analogues, has been reviewed with a focus on the chemical and physical properties of these fascinating species. The presence of a heteroatom has an impact on the stability of the heteropines, of which to date only the parent oxepine has been isolated. The generation of these (transient) heterocycles allowed the development of a rich chemistry, which has been extensively explored using the full toolbox of physical organic chemistry.