Cyclopropanes with aromatic rings

Hydrogen bromide adds to acetylene to form vinyl bromide or ethyHdene bromide, depending on stoichiometry. The acid cleaves acycHc and cycHc ethers. It adds to the cyclopropane group by ring-opening. Additions to quinones afford bromohydroquinones. Hydrobromic acid and aldehydes can be used to introduce bromoalkyl groups into various molecules. For example, reaction with formaldehyde and an alcohol produces a bromomethyl ether. Bromomethylation of aromatic nuclei can be carried out with formaldehyde and hydrobromic acid (6). 

We have examined the above-described series of trans- and c/s-2-fluoro-2-phenylcyclopropylamine analogues (60a-d, 61a-d) as inhibitors of recombinant human liver MAO A and B [134]. The presence of fluorine attached to a cyclopropane ring, especially for frans-isomer 8a, was found to result in an increase in inhibitory activity toward both MAO A and B (Table 4). In addition, p-substitution of electron-withdrawing groups, such as Cl and F, in the aromatic ring of the frans-isomers (60b-d) increased the inhibition of both enzymes. On the other hand, the introduction of fluorine at 2-position of c/s-isomer 8b resulted in loss of inhibitory activity for both MAO A and B, and no further p-aromatic substitution for c/s-isomer greatly affected on the inhibitory activity with either enzymes. In addition, both MAO A and B were selectively inhibited by the (1S,2S)-enantiomer of 60a, while no inhibition was observed with the (1f ,2f )-enantiomer [134]. As already described in the former section, several questions on the mechanistic pathway for MAO inhibition by cyclopropylamines still remain. However,... 

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. 

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). 

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