Synchronous 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). 

Cope himself formulated this transformation as what would now be called a synchronous pericyclic reaction . This interpretation was supported by Woodward-Hoffmann s analysis of pericyclic processes. The Cope rearrangement of 1,5-hexadiene derivatives was regarded therefore for a long time as a classical example of an allowed pericyclic reaction... 

The unhomogeneous composition of the products generated by the photochemical reaction is due to another mechanism. While the thermal isomerization of 1,5-dienes proceeds via a cyclic transition state in a synchronous sense, the photochemically induced transformation causes a reorientation of the allyl radicals generated from the educts. Warming up the reaction mixture to 100°C activates a complete transfer from 4c to 5c) of all isomers. This step may be explained by a radical CC bond split of the 1,2-diphenylethylene unit. Since the isomerization of the diastereomeric compound 4c to 5c is activated at much lower temperatures than for the Cope rearrangement (from 3c to 4c), it is clear that the thermal transfer exclusively forms the twofold changed product. 

On the basis of MlNDO/3 calculations, Dewar argued for a non-concerted mechanism for the parent Cope rearrangement, involving formation of cyclohexane-1,4-diyl (A) as an intermediate [12]. Several years later, Dewar published another paper in which he boldly claimed that multi-bond reactions, such as the Cope rearrangement, cannot, in general, involve synchronous bond making and bond breaking [13]. 

The simulated (6/6)CASSCF calculations were performed at several partially optimized Ciu geometries. The calculations found that the Cope TS has an interallylic separation of / = 2.062 A, which is close to that of / = 2.023 A for the fully optimized RHF/3-21G TS. Thus, the simulated (6/6)CASSCF/3-21G calculations found that bond making and bond breaking occur synchronously in the Cope rearrangement via an aromatic TS (B). 

Cope rearrangements of 2,6-disubstituted bicyclo[5,l,0]octa-2,5-dienes have been studied to determine the extent of bond making and bond breaking at the transition state. The interpretation of the results was complicated by the enforced boat-transition state, but comparison with polycyclic systems supports the hypothesis that, unlike Cope rearrangements in acyclic dienes, bond cleavage is at least synchronous with bond formation. ... 

There has been a controversy concerning the mechanism of the chair Cope rearrangement for many years (see ref. 7 and papers cited therein) Conflicting experimental and theoretical studies provide evidence to support both a synchronous mechanism with an "aromatic transition state... 

From a theoretical point of view, in multi-bond reactions it is essential to use a wavefunction where the possibility of biradical and aromatic transition states can be treated with a balanced level of accuracy. Thus the MC-SCF results of Morokuma et al [21] on the Cope rearrangement of the "model" reaction of 1,5 hexadiene are very convincing and provide reliable evidence that the lowest energy pathway for the "model" reaction is the synchronous one with the biradical intermediate lying 22 Kcal mole higher in energy than the synchronous transition state. 

Interest in the mechanism and stereochemistry of the Cope rearrangement, which attracted considerable attention twenty-odd years ago [13], has recently been rekindled after several years of comparative neglect, and is presently the subject of a considerable amount of critical discussion, with particular emphasis on the synchronicity of the bond-breaking and bond-forming processes [17]. 

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