Aromatic-Cope rearrangement

Sol 3. (i) l,l-Divinyl-2-phenylcyclopropane derivative (I) on heating undergoes a vinylcyclopropane rearrangement to give vinylcyclopentene derivative (II). In this reaction one of the vinyl groups of I participates in the reaction and the other is a substituent. The major spirolactam (ID) is formed by a reversible aromatic Cope rearrangement followed by an irreversible ene reaction. In this... 

One of the first examples of the use of the aromatic-Cope rearrangement in synthesis was developed in the Jung laboratories toward the synthesis of ( )-coronafacic acid. Featuring the participation of a benzofuran as the aromatic partner in an anionic oxy-Cope rearrangement, the reaction of 249 proceeds to give the tetracyclic product 250 as a single diastereomer. 

Compared to the example above, the participation of benzene in the aromatic-Cope rearrangement has been more difficult to achieve. However, it has recently been utilized for the preparation of helicenes and other polycyclic compounds.One of the first and most impressive demonstrations of this reaction was utilized in the synthesis of tricyclic compounds such as 252. As above, the anionic oxy-aromatic-Cope rearrangement of 251 proceeded in excellent yield to give 252, resulting from rearomatization of the benzene ring. 

A symmetry approach to the effect of temperature and substitution on Cope rearrangements has revealed that with increasing temperature the loss of symmetry can be considered as a collective variable which has a positive linear relationship with temperature. The results of an aromatic Cope rearrangement of a trans-l-aryl-2-ethenylcyclobutanecarbonitrile have been reported for the construction of the fused benzocyclooctene ring. The effects of gem-dimethyl substitution on the cyclopropane, alkene geometry, relative stereochemistry of the cyclopropane, and steric and electronic effects of functional groups on the thermal Cope rearrangement of divinylcyclopropanes have been reported (Scheme 10). " ... 

If both ortho positions bear substituents other than hydrogen, the allyl group will further migrate to the para position. This reaction is called the para-Claisen rearrangement. The formation of the para-substituted phenol can be explained by an initial Claisen rearrangement to an ortho-2l y intermediate which cannot tautomerize to an aromatic o-allylphenol, followed by a Cope rearrangement to the p-allyl intermediate which can tautomerize to the p-allylphenol e.g. 6 ... 

Pd2(dba)3/l,4-bis(diphenylphosphino)butane (DPPB) in the presence of 2-mercaptobenzoic acid <95TL1267>. The Af-allylindolines can be easily oxidized to the corresponding indoles at room temperature with o-chloranil. Additionally, Al-allylanilines were also found to undergo aromatic 3-aza-Cope rearrangements in the presence of Zeolite catalysts to give indoline derivatives as the major product <96TL5281>. 

The reaction with the siloxy derivative 29 is an interesting example because the product 30 is a 1,5-dicarbonyl derivative (Equation (36)).96 1,5-Dicarbonyls are classically prepared by a Michael addition, but the synthesis of 30 by a Michael addition is not possible because it would require addition to the keto form of 1-naphthol. The acetoxy derivative 31 resulted in a different outcome, leading to the direct synthesis of the naphthalene derivative 32 (Equation (37)).96 In this case, the combined C-H activation/Cope rearrangement intermediate was aromatized by elimination of acetic acid before undergoing a reverse Cope rearrangement. 

Along with a very wide synthetic application the Cope rearrangement continues to be a subject of intense debates. The key mechanistic question is whether the rearrangement of 1,5-hexadiene derivatives is concerted and passes via a six-electron aromatic transition state, or whether it involves the formation of a diradical intermediate, i.e. a cyclization-cleavage mechanism. In the former case, bond making and bond breaking occur synchronously (a survey of this question has been published210). 

The Cope rearrangement mechanism can be also strongly affected by other substituents. Thus, the normal electrocyclic process in the thermal isomerization of divinyl aromatics has been suppressed relative to the thermolysis of l,2-bis(trifluorovinyl)naphthalene 438 (in benzene, at 193 °C, 24 h)231. Three major products 440-442 were isolated from the reaction mixture, but none of them was the expected product 439. Also formed in low... 

Apparently, the aromatization of the heterocyclic cation serves as a driving force of the Cope rearrangement in the transformation of the 3-formyl-4-allyl-4//-pyrane (481) into poly-substituted pyrylium salt 483 which presumably proceeds via 482 (equation 183)242. 

The SnCU-catalysed Claisen and Cope rearrangements of A -allylanilines and N-allylenamines, and the effect of meffl-substituents in the aromatic ring on the Claisen aromatic amino rearrangement of a series of fluorinated anilines, have been investigated. 

NMR and kinetic studies have been carried out on the antibody-catalysed oxy-Cope rearrangement of hexadiene (100) to aldehyde (101). An aromatic oxy-Cope rearrangement involving a benzene ring [see (102) (103)] has been observed to... 

Sheradsky has found that the hydroxyl function of a ketoxime such as acetophenone oxime can be made to react with DMAD when the reaction is carried out in methanol with a basic catalyst, to give mixture of the fumarate and maleate isomers (164) in the ratio 2 1. This mixture on heating undergoes a hetero-Cope rearrangement followed by cyclization and dehydration to give dimethyl 5-phenylpyrrole-2,3-dicarboxylate (168) (Scheme 25). Similarly, Heindel and Chun have reported that vinyl ether adducts (171), obtained by the condensation of arylamide oximes with DMAD, get thermally converted into oxa-diazolines (172) or imidazolinones (174), depending on the reaction conditions. A similar reaction occurs with aromatic amidoxime-methyl propiolate adducts to give imidazoles (170) (Scheme 26). 1,2,4-Dioxazoles have been reported to be formed in the reaction of hydrox-amic acids with DMAD. - ... 

There appears to be much interest in the mechanism of various pericyclic transfer-mations, particularly of the Cope rearrangement. A pair of interacting allyl radicals, an aromatic species, or a 1,4-cyclohexanediyl diradical are the possible intermediates and transition states for the rearrangement represented here as resonance hybrids in the transformation of 1,5-hexadiene (Scheme 4.16). Two high-order theoretical studies indicate that the Cope rearrangement is concerted and proceeds via an aromatic chair transition state (33).362,364... 

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