Norcaradiene, equilibrium with cycloheptatrien

Arenes suffer dearomatization via cyclopropanation upon reaction with a-diazocarbonyl compounds (Btlchner reaction) [76]. Initially formed norcaradiene products are usually present in equilibrium with cycloheptatrienes formed via electrocyclic cyclopropane ring opening. The reaction is dramatically promoted by transition metal catalysts (usually Cu(I) or Rh(II) complexes) that give metal-stabilized carbenoids upon reaction with diazo compounds. Inter- and intramolecular manifolds are known, and asymmetric variants employing substrate control and chiral transition metal catalysts have been developed [77]. Effective chiral catalysts for intramolecular Buchner reactions include Rh Cmandelate), rhodium carboxamidates, and Cu(I)-bis(oxazolines). While enantioselectivities as high as 95% have been reported, more modest levels of asymmetric induction are typically observed. 

The presence of a locked norcaradiene is however not a prerequisite for introduction of the central double bond of a cycloproparene. Exposure of the 1,6-diha-logenated cycloheptatriene 50 to n-BuLi also results in formation of benzocyclopropene (1) via 69, despite of the unfavorable position of the cyclohep-tatriene-norcaradiene equilibrium. The method is, however, of limited interest, since the most convenient access to 1,6-dihalogenocycloheptatrienes starts with benzocyclopropene (1). ... 

The bicyclic 3,4-dihydropyridines (51) and (53) illustrate that the electrocyclic ring opening is sensitive to substituents (80TL599). The 3,4-dihydropyridine (51) has been observed to be in equilibrium with the azepine (50). Consistent with the analogous carbocyclic system, norcaradiene-cycloheptatriene, the monocycle (50) is the predominant species present in this equilibrium. In contrast, the dimethyl derivatives (52) and (53) exist almost exclusively in the 3,4-dihydropyridine form. A greater steric interaction between these methyl substituents in (52) was given in explanation of these observations. 

Further experimental and theoretical studies on the rotational barriers of the metal fragment in (cycloheptatriene)Cr(CO)3 complexes195 suggest that (cycloheptatriene)-Cr(CO)3 complexes in general are in equilibrium with their norcaradiene valence isomers and their ground state conformation is controlled by the same electronic factors which effect the cycloheptatriene-norcaradiene equilibrium195. 

In one famous case, the release of ring strain is almost exactly counterbalanced by the formation of a a bond at the expense of a it bond. Cycloheptatriene exists in equilibrium with a blcyclic isomer known as norcaradiene. Usually cycloheptatriene is the major component of the equilibrium, but the norcaradiene structure is favoured if R is an electron-withdrawing group. 

A wide range of 3,3-disubstituted cyclopropenes, e.g. the dimethyl and diphenyl derivatives, as well as spiro[2.4]hept-l-ene or 6,6-dimethyl-4,8-dioxaspiro[2.5]oct-l-ene, can thus be reacted with a variety of mono- and disubstituted alkynes. Usually, the chemoselectivity of this cy-clocotrimerization reaction is remarkably high. The norcaradiene derivatives initially obtained are in equilibrium with the valence tautomeric cycloheptatrienes. The equilibrium ratio of the valence tautomers is strongly dependent on the position and kind of substituents, especially those in the 7-position of the newly formed norcaradienes and cycloheptatrienes. When one or two phenyl groups are present in this position, only norcaradiene products can be detected by and NMR spectroscopy at room temperature, whereas in the case of methyl substituents, both valence tautomers are formed in almost equal amounts. When cyclic alkynes, such as cyclooctyne, are employed in the reaction, only norcaradienes are formed regardless of the substituents present in the cyclopropene cosubstrate. ... 

The nature of the benzene substituents strongly influences the fate of the reaction, controlling the position and the number of reactive double bonds. Note that at 20 °C, the norcaradienes 2 are not in equilibrium with their cycloheptatriene isomers. 

However, it has been shown that substituents can change the position of the cycloheptatriene/ norcaradiene equilibrium. Thus n-electron-withdrawing substituents in 1 (X = Y = CN X = COjH, Y = H ) are able to stabilize the norcaradiene structure by shortening the distal (C2-C3) bond and lengthening the vicinal (C1-C2, C1-C3) bonds. With 7r-electron-do-nating substituents the situation is more complex. Only strong n-donors (e.g. 0 , CHj) effect stabilization by lengthening the cyclopropane bonds."... 

The Buchner reaction describes cyclopropanation of an aromatic double bond with the a-ketocarbene derived from an a-diazocarbonyl compound 1 to produce an unstable norcaradiene intermediate 2, which is in thermal equilibrium with the more stable cycloheptatriene tautomer 3. This tautomer undergoes thermally or photochemically induced electrocyclic ring opening to give other cycloheptatriene isomers A-6)... 

Substrate-controlled stereoselective dearomatizations provide cycloheptatriene derivatives in high diastereomeric excess, and the reaction has been used to prepare 7-membered ring systems found in several natural products. Scheme 15.27a illustrates the Rh(II)-catalyzed conversion of diazo derivative 72 to polycyclic cycloheptatriene 73, which was subsequently converted to har-ringtonolide [78]. Note that the initial cycloheptatriene product of the Buchner reaction is converted to a more stable isomer by the action of DBU. In some instances, intramolecular Buchner reactions afford norcaradiene products that are not in equilibrium with the corresponding cycloheptatrienes. These examples arise as a consequence of conformational constraints inherent in the substrates. Cu-catalyzed Buchner reactions have been anployed to access derivatives of stable norcaradiene fragments found in several natural products (e.g., gibberellin GA j and (-r)-salvileucalin B, Scheme 15.27b and c, respectively) [79]. 

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). 

Although nonaromatic cyclic alkaoligoenes always react with transient phosphorus-substituted carbenes to give 1 1 adducts, aromatic derivatives sometimes give rise to a mixture of 1 1 and 1 2 adducts. Numerous bicyclo[4.1.0]hepta-2,4-dienes (norcaradienes) have been prepared by reacting transient phosphorus-substituted carbenes with aromatic compounds in order to study the influence of the substituents on the norcaradiene-cycloheptatriene equilibrium. Benzene itself and its functionalized derivatives, in which the three bonds are not equivalent, will be reviewed in separate sections. 

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