Aromatic systems cycloheptatriene

The reaction of carbenoids with aromatic systems was first reported by Buchner and coworkers in the 1890s.6 The reaction offers a direct entry to cycloheptatrienes and has been used to synthesize tropones, tropolones and azulenes.6 Neither the thermal nor copper-catalyzed reactions, however, proceed in good yield. The problems associated with these transformations were clearly demonstrated in a recent reexamination of die thermal decomposition of ethyl diazoacetate in excess anisole (137).129 A careful analysis of the reaction mixture revealed the presence of seven components (138-144) in 34% overall yield (Scheme 29). The cycloheptatrienes (138M142) were considered to be formed by cyclopropanation followed by electrocyclic ring opening of the resulting norcaradienes. A mixture of products arose because the cyclopropanation was not regioselective and, also, the initially formed cycloheptatrienes were labile under the reaction conditions. 

The products formed in these reactions are very sensitive to the functionality on the carbenoid. A study of Schechter and coworkers132 using 2-diazo-1,3-indandione (152) nicely illustrates this point. The resulting carbenoid would be expected to be more electrophilic than the one generated from alkyl diazoacetate and consequently ihodium(II) acetate could be used as catalyst. The alkylation products (153) were formed in high yields without any evidence of cycloheptatrienes (Scheme 33). As can be seen in the case for anisole, the reaction was much more selective than the rhodium(II)-catalyzed decomposition of ethyl diazoacetate (Scheme 31), resulting in the exclusive formation of the para product. Application of this alkylation process to the synthesis of a novel p-quinodimethane has been reported.133 Similar alkylation products were formed when dimethyl diazomalonate was decomposed in the presence of aromatic systems, but as these earlier studies134 were carried out either photochemically or by copper catalysis, side reactions also occurred, as can be seen in the reaction with toluene (equation 36). 

In the cycloheptatriene molecule there are three double bonds and hence six p orbitals if a hydride anion is removed from the only methylene unit and that carbon is re-hybridised from sp to sp so as to create an empty p orbital, this completes the circuit of p orbitals around the cycloheptane ring. Then there is a continuous series of p orbitals that contain six n electrons, which gives rise to an aromatic system. 

Unlike cyclopentadiene, cycloheptatriene is not an acidic hydrocarbon its pK is about 36. If a proton could be abstracted from cycloheptatriene, the resulting anion would have eight it-electrons and would be an unstable, anti-aromatic system. 

Addition of carbenes to aromatic systems leads to ring-expanded products. Methylene itself, formed by photolysis of diazomethane, adds to benzene to form cycloheptatriene in 32% yield a small amount of toluene is also formed by an insertion reaction. The cycloheptatriene is formed by a Cope rearrangement of the intermediate cyclopropane (a norcaradiene). More satisfactory is the reaction of benzene with diazomethane in the presence of copper salts, such as copper(I) chloride, which gives cycloheptatriene in 85% yield (4.87). The reaction is general for aromatic systems, substituted benzenes giving mixtures of the corresponding substituted cycloheptatrienes. 

Quinones, as oxidation products of aromatic systems, are capable of being reduced back to aromatic systems and some quinones are used particularly for this purpose. For example, as shown in Scheme 6.79, 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ) can be used to oxidize 1,2,3,4-tetrahydronaphthalene (tetraUn, CioFli2) to naphthalene (CioHg) while it is reduced to the corresponding phenol, 2,3-dichloro-5,6-dicyanohydroquinone (DDQ H2). Further, while reduced to the same product, DDQ is also capable of oxidizing 1,3,5-cycloheptatriene to the corresponding, aromatic cycloheptatrienyl cation and, if the oxidation is carried out in perchloric acid, the perchlorate of the cation is an isolable salt (Scheme 6.79). 

In some cases, a resonance structure is required to see an aromatic system. The increased stability associated with an aromatic system is found for the structure, although the compounds do not appear aromatic unless the resonance structure is considered. Azulene, which can be drawn as a cyclopentadienyl anion fused to a cycloheptatriene cation, and cyclopropenone, which can be written as possessing a cyclopropenyl cation, are two examples (see margin). 

When 1,3,5-cycloheptatriene is heated with bromine, a stable salt is formed, cycloheptatrienyl bromide. In this molecule, the organic cation contains six delocalized tt electrons, and the positive charge is equally distributed over seven carbons (as shown in the electrostatic potential map in the margin). Even though it is a carbocation, the system is remarkably unreactive, as is expected for an aromatic system. In contrast, the cycloheptatrienyl anion is antiaromatic, as indicated by the much lower acidity of cycloheptatriene (pA"a = 39) compared with that of cyclopentadiene. 

The carbocation is aromatic the hydrocarbon is not Although cycloheptatriene has six TT electrons m a conjugated system the ends of the triene system are separated by an sp hybridized carbon which prevents continuous tt electron delocalization... 

Oxepin and its derivatives have attracted attention for several reasons. Oxepin is closely related to cycloheptatriene and its aza analog azepine and it is a potential antiaromatic system with 871-elcctrons. Oxepin can undergo valence isomerization to benzene oxide, and the isomeric benzene oxide is the first step in the metabolic oxidation of aromatic compounds by the enzyme monooxygenase. 

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.). 

SAMPLE SOLUTION (a) Cycloheptatriene (compound A) is not aromatic because, although it does contain six it electrons, its conjugated system of three double bonds does not close on itself—it lacks cyclic conjugation. The CH2 group prevents cyclic delocalization of the tt electrons. ... 

Decomposition of l-diazo-4-arylbutan-2-ones offers a direct entry to bicyclo[5.3.0]decatrienones and the approach has been extensively used by Scott and coworkers to synthesize substituted azulenes.137 Respectable yields were obtained with copper catalysis,137 but a more recent study24 showed that rho-dium(ll) acetate was much more effective, generating bicyclo[5.3.0]decatrienones (154) under mild conditions in excess of 90% yield (Scheme 34). The cycloheptatrienes (154) were acid labile and on treatment with TFA rearranged cleanly to 2-tetralones (155), presumably via norcaradiene intermediates (156). Substituents on the aromatic ring exerted considerable effect on the course of the reaction. With m-methoxy-substituted systems the 2-tetralone was directly formed. Thus, it appeared that rearrangement of (156) to (154) was kinetically favored, but under acidic conditions or with appropriate functionality, equilibration to the 2-tetralone (155) occurred. 

However, homoaromatic stabilisation appears to be absent in neutral systems. Homobenzene (cycloheptatriene) 1.23 and trishomobenzene (triquinacene) 1.26, even though transannular overlap looks feasible, show no aromatic properties. In both cases, the conventional structures 1.23 and 1.24, and 1.26 and 1.27 are lower in energy than the homoaromatic structures 1.25 and 1.28, which appear to be close to the transition structures for the interconversion. 

Photolysis of a-diazo esters in the presence of benzene or benzene derivatives often results in [2-1-1] cycloaddition of the intermediate acylcarbene to the aromatic ring, thus providing access to the norcaradiene (bicyclo[4.1.0]hepta-2,5-diene)/cyclohepta-l,3,5-triene valence equilibrium. The diverse effects that influence this equilibrium have been discussed (see Houben-Weyl, Vol. 4/3, p509). To summarize, the 7-monosubstituted systems obtained from a-diazoacetic esters exist completely in the cycloheptatriene form, whereas a number of 7,7-disubstituted compounds maintain a rapid valence equilibrium in solution. On the other hand, several stable 7-cyanonor-caradienes are known which have a second 7t-acceptor substituent at C7 (see Section 1.2.1.2.4.3). Subsequent photochemical isomerization reactions of the cycloheptatriene form may destroy the norcaradiene/cycloheptatriene valence equilibrium. Cyclopropanation of the aromatic ring often must compete with other reactions of the acylcarbene, such as insertion into an aromatic C H bond or in the benzylic C H bond of alkylbenzenes (Table 7). 

An ingenious synthesis of steroidal annulenes has appeared. The close relationship of annulenes to the classical aromatic substance naphthalene stimulated the synthesis of l,6-methano-[10]annuleno-steroids, which are analogues of equilenin (97). The y,5-cyclopropyl-a -unsaturated ketone (98) was the initial target. Treatment of the cyclopropyl ketone (98) with acetic anhydride and methyl orthoformate in the presence of an acid catalyst then gave (99). Conversion of the cycloheptatriene (99) into the requisite 10 c-electron system (100) was then accomplished by dehydrogenation. ... 

By analogy with azepines and 1,2-diazepines <8iH(i5)i569>, the fully unsaturated 1,4-diazepines with their 8ti electron system should not be aromatic but should behave as cyclic polyenes and, hke cycloheptatriene should have a chair or boat conformation. If the ring system were able to become planar, one would expect the fully unsaturated 1,4-diazepines to be anti-aromatic. Additional evidence for the nonaromatic nature of the 1,4-diazepines is provided by the NMR spectra, where the ring protons are found in the typical range for alkenic protons, i.e. 5 5.0-7.0. 

Two possible pathways were envisioned for the reaction (a) cyclopropane to propylene-like rearrangement followed by 1,5-hydrogen shifts, that can equilibrate C4 and C6 as well as C3 and Cl with a slower 1,5-deuterium shift (due to the primary isotope effect) and (b) the second pathway would involve a retro-electrocyclization to a cycloheptatriene destroying the aromatic it system in the process, and this undergoes a 1,5-deuterium shift to the 1,2-benzocycloheptatriene which subsequently undergoes a 1,5-hydrogen shift to equilibrate C4 and C6 but also must equilibrate C3 with Cl. Further, a 1,5-deuterium shift in the 7-deuterio material gives the isomer from path (a) (Scheme 12.8). 

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