Hexadienes, pericyclic rearrangements

Two other important sigmatropic reactions are the Claisen rearrangement of an allyl aryl ether discussed in Section 18.4 and the Cope rearrangement of a 1,5-hexadiene. These two, along with the Diels-Alder reaction, are the most useful pericyclic reactions for organic synthesis many thousands of examples of all three are known. Note that the Claisen rearrangement occurs with both allylic aryl ethers and allylic vinylic ethers. 

These reactions, called electrocyclic rearrangements, take place by pericyclic mechanisms. The evidence comes from stereochemical studies, which show a remarkable stereospecificity whose direction depends on whether the reaction is induced by heat or light. For example, it was found for the thermal reaction that cis-3,4-dimethylcyclobutene gave only cw,tran5-2,4-hexadiene, while the trans isomer gave only the trans-trans diene... 

As we have indicated with our arrows, the mechanism of the uncatalyzed Cope rearrangement is a simple six-centered pericyclic process. Since the mechanism is so simple, it has been possible to study some rather subtle points, among them the question of whether the six-membered transition state is in the boat or the chair form. ° For the case of 3,4-dimethyl-l,5-hexadiene it was demonstrated conclusively that the transition state is in the chair form. This was shown by the stereospecific nature of the reaction The meso isomer gave the cis-trans product, while the ( ) compound gave the trans-trans diene. If the transition state is in the chair form (e.g., taking the meso isomer), one methyl must be axial and the other equatorial and the product must be the cis-trans alkene ... 

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... 

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... 

The X-ray crystal structure for AZ-28 has a variety of structural features that are consistent with the proposed mechanism operative for the oxy-Cope rearrangement. The antibody binds the transition stage analog in a chair-like conformation, consistent with the preferred chair transition state for this pericyclic reaction (Doering and Roth, 1962). The positions of the C-2 and C-5 atoms are fixed in the antibody-bound hapten molecule in a similar fashion, the C-2 and C-5 positions in the hexadiene substrate should be held in a fixed position by conserved van der Waals interactions locking in the two phenyl substituents in the antibody combining site. This bound conformation of the acyclic (47T + 2er) system of the hexadiene substrate should enforce a molecular conformation close to the transition state for the rearrangement reaction, consistent with the catalysis observed for AZ-28. 

A significant difference between the Claisen and the Cope rearrangement is that both C-3 and C-4 in the pericyclic carbon framework may be stereogenic centers. The stereochemical outcome of such rearrangements has been demonstrated by the classical investigations on the rearrangement of 3,4-dimethyl-l, 5-hexadienes (32)274. For example, the rearrangement of meso-32 results in the nearly exclusive formation of ( ,Z)-2,6-octadiene (33) via a chair transition state conformation, whereas rac-32 affords a 90 f 0 mixture of the ( , )- and (Z.Z)-iso-mers via chair A and chair B. 

On the basis of stereochemical and kinetic investigations and quantum-mechanical calculations, most Cope rearrangements are regarded as being pericyclic processes [25, 102, 103]. The van der Waals volumes calculated for the parent 1,5-hexadiene... 

A volume expansion is expected for homolytic bond dissociations as already pointed out in the Introduction. This expectation has been confirmed for several homolytic bond cleavages showing positive activation volumes near AV - +10 cm mol [123]. The analysis of the pressure effect on the cleavage of azo compounds is however, complicated by the possibility of one- and two-bond scission processes [124]. The benzylic and benzhydrylic 1,4-shifts in the substituted pyr-idiminiumoxides (Scheme 2.29, entry (1)) [125] illustrate the utility of high pressure for the distinction between a pericyclic and dissociative mechanism comparable to the rearrangement of l,3,4,6-tetraphenyl-l,5-hexadiene which has already... 

If the pericyclic ring has an even number of atoms, both the reactants and the transition state will have even conjugated systems. Such reactions are of EE type. Furthermore, the course of the reaction depends on the topology of the overlap of AOs in the transition state and this is unrelated to the structures of the reactants or products. The reactions are of anti-BEP type and are therefore classed as EEj. This is evident from the examples given in equation (5.294) or (5.295). The stereospecificity of the reactions is clearly unrelated to their heats of reaction since both cis- and frans-3,4-dimethylcyclo-butene can rearrange without steric restraints to any of the isomeric 2,4-hexadienes. 

The best way to understand how orbital symmetry affects pericyclic reactions is to look at some examples. Let s look hrst at a group of polyene rearrangements called electrocyclic reactions. An electrocyclic reaction is a pericyclic process that involves the cyclization of a conjugated acyclic polyene. One tt bond is broken, the other tt bonds change position, a new a bond is formed, and a cyclic compound results. For example, a conjugated triene can be converted into a cyclo-hexadiene, and a conjugated diene can be converted into a cyclobutene. 

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