Pericyclic reactions Cope rearrangement

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. 

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 ... 

As expected, some sequences also occur where a domino anionic/pericyclic process is followed by another bond-forming reaction. An example of this is an anionic/per-icyclic/anionic sequence such as the domino iminium ion formation/aza-Cope/ imino aldol (Mannich) process, which has often been used in organic synthesis, especially to construct the pyrrolidine framework. The group of Brummond [450] has recently used this approach to synthesize the core structure 2-885 of the immunosuppressant FR 901483 (2-886) [451] (Scheme 2.197). The process is most likely initiated by the acid-catalyzed formation of the iminium ion 2-882. There follows an aza-Cope rearrangement to produce 2-883, which cyclizes under formation of the aldehyde 2-884. As this compound is rather unstable, it was transformed into the stable acetal 2-885. The proposed intermediate 2-880 is quite unusual as it does not obey Bredf s rule. Recently, this approach was used successfully for a formal total synthesis of FR 901483 2-886 [452]. 

The second largest group of pericyclic domino reactions starts with a sigmatropic rearrangement, which is most often a Claisen or an oxa- and aza-Cope rearrangement however, some processes also exist with a 2,3-sigmatropic rearrangement as the second step. 

Isopolar activated complexes differ very little or not at all in charge separation or charge distribution from the corresponding initial reactants. These complexes are formed in pericyclic reactions such as Diels-Alder cydoadditions and the Cope rearrangement. 

In addition to the numerous pericyclic aromatic TSs, other reactions deserve attention. These include the Cope and Claisen rearrangements, the pericyclic reactions with Mobius TSs, the Bergman cyclizations [77,116], and the TSs for 1,5-H shifts [100,117],... 

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... 

It has been established that the course of the sequential pericyclic reaction of cyclopentadienones with acyclic conjugated alkadienes depends on the reaction temperature, thermal treatment at low temperatures affording 3a,4,7,7a-tetrahydroinden-l-one derivatives by way of a Cope rearrangement (see Scheme 38). Roman et al have developed an efficient stereoselective synthesis of enantiomerically pure i-nitrotricyclo[5.2.2.0 ]undeca-3,8-dienes via a tandem consecutive asymmetric Diels-Alder-Cope rearrangement (see Scheme 39). Adducts... 

Boland, W., Pohnert, G., and Maier, I., Pericyclic reactions in nature spontaneous Cope rearrangement inactivates algal pheremones, Angew. Chem. Int. Ed., 34, 1602, 1995. 

Pohnert, G. and Boland, W., Pericyclic reactions in nature synthesis and Cope rearrangement of thermolabile bis-alkenylcyclopropanes from female gametes of marine brown algae (Phaeophyceae), Tetrahedron, 53, 13681, 1997. 

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. 

The ability of the PC double bond within tetraphosphahexadienes to participate in pericyclic reactions initiated interest in the synthesis of additional phosphahexadienes and studies of their properties. Attempts to synthesize 1,6-diphosphahexadiene a via a [1,1 ] Cope rearrangement out of 3,4-diphosphahexa-l,5-diene, derived from l,2-dipotassium-l,2-diphenyl diphosphide and vinylbromide, were not successful when carried out up to the temperature of decomposition (above 120°C). 

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