Cope rearrangement system

Like the Cope rearrangement, the Claisen rearrangement is sensitive to substituents on the reacting system. Cyano groups promote the rearrangement by a factor of 10 at positions 2 and 4 and have smaller effects at the other positions, as shown below. Data are also available for methoxy groups at positions 2, 4, 5, and 6. ... 

The structures in the (1,0) and (0,1) comers are not necessarily stable species, they may correspond to hypothetical structures. In the Cope rearrangement it appears that the reaction only involves a single TS, independently of the number and nature of substituents. The reaction path may change from B A C depending on the system, but there are no intermediates along the reaction coordinate. 

The required temperatures for the Cope rearrangement are generally lower, if the starting material contains a substituent at C-3 or C-4 which can form a conjugated system with one of the new double bonds. 

Based on the successful series of transformations summarized in Scheme 1, Schreiber and Santini developed an efficient and elegant synthesis of periplanone B (1),8 the potent sex pheromone of the American cockroach, Periplaneta americana. This work constitutes the second total synthesis of periplanone B, and it was reported approximately five years after the landmark periplanone B synthesis by W.C. Still9 (see Chapter 13). As in the first synthesis by Still, Schreiber s approach to periplanone B takes full advantage of the facility with which functionalized 5-cyclodecen-l-one systems can be constructed via anionic oxy-Cope rearrangements of readily available divinylcyclohexanols.5 7 In addition, both syntheses of periplanone B masterfully use the conformational preferences of cyclo-decanoid frameworks to control the stereo- and regiochemical course of reactions carried out on the periphery of such ring systems.10... 

Occasionally, addition products of 4//-l,2,4-triazole-3,5-diones or diazenedicarboxylic esters and oxepins have been obtained whose formation can be rationalized by an addition to the 2,4-diene system in the oxepin, e.g. formation of 10.190191 In these cases, the primary adduct usually cannot be isolated, because it undergoes a hetero-Cope rearrangement to a tricyclic or bicyclic structure in which the oxepin oxygen has become part of a carbonyl function.190 191,227... 

The Rh2(DOSP)4 catalysts (6b) of Davies have proven to be remarkably effective for highly enantioselective cydopropanation reactions of aryl- and vinyl-diazoacetates [2]. The discovery that enantiocontrol could be enhanced when reactions were performed in pentane [35] added advantages that could be attributed to the solvent-directed orientation of chiral attachments of the ligand carboxylates [59]. In addition to the synthesis of (+)-sertraline (1) [6], the uses of this methodology have been extended to the construction of cyclopropane amino acids (Eq. 3) [35], the synthesis of tricyclic systems such as 22 (Eq. 4) [60], and, as an example of tandem cyclopropanation-Cope rearrangement, an efficient asymmetric synthesis of epi-tremulane 23 (Eq. 5) [61]. 

When there is a hydroxy substituent at C(3) of the diene system, the Cope rearrangement product is an enol that is subsequently converted to the corresponding... 

The 2-azonia analog of the Cope rearrangement is estimated to be accelerated by 106, relative to the unsubstituted system.270 The product of the rearrangement is an isomeric iminium ion, which is a mild electrophile. In synthetic applications, the reaction is often designed to generate this electrophilic site in a position that can lead to a cyclization by reaction with a nucleophilic site. For example, the presence of a 4-hydroxy substituent generates an enol that can react with the iminiun ion intermediate to form a five-membered ring.271... 

HO of a system consisting of two ethylenes connected by a weak pa bond a) (i) Cope rearrangement... 

SCHEME 20. Activation volumes of Cope rearrangements in unpolar 1,5-hexadiene systems... 

In the reaction of disubstituted alkynes, 1,3-migration of the acetate takes place to give allenyl esters that can be versatile substrates, especially for [3,3]-Cope rearrangements.333 1,5-Enynes have proved to be versatile substrates for the preparation of perfumery agents such as sabinol334 and sabina ketone.335 Transannular systems undergo similar reactions.336... 

The Cope and oxy-Cope rearrangement are very useful in organic synthesis, particularly when the 1,5-diene system is incorporated in a ring, then intringuing cyclic compounds may result. Also, the Cope and oxy-Cope rearrangements are greatly facilitated for a cw-1,2-divinylcyclobutane (Eq. 15)), resulting in the formation... 

There are also instances where a system undergoes Cope rearrangement through different possibilities. This is afforded by the examples of hexadiene. The alternatives are of two types. 

The first step is addition of Cl 1 to C4. We still need to form C10-C1 and break C4-C3. Since we have a 1,5-diene (Cl 1=C10-C4-C3-C2=C1), we can do an oxy-Cope rearrangement. This gives a 5-8 system in which we only have to form the C4-C2 bond. C4 is neither nucleophilic nor electrophilic, while Cl 1 is nucleophilic (conjugation from OSiMe3). Upon quenching with water, however, C4 becomes an electrophilic carbonyl C, whereupon Cl 1 attacks with concomitant desilylation of O to give the product. 

In the synthesis of ( )-palominol and ( )-dolabellatrienone from famesol, Corey and Kania84 employed a dianion accelerated oxy-Cope rearrangement to form the 11,5-trans-fused ring system of the dolabellanes. Diol 112 was treated with potassium hydride in THF to afford a 1 1 mixture of products with iraws-ll,5-fused ring systems, 113 and... 

Fivefold degenerate reversible [3,3]-sigmatropic shifts were first reported in 1988116,117 in the CPD-amidine system 257, where AG g = 117 to 120 kJmol-1 (equation 88) (for aza-Cope rearrangements see Section IV.E.2). In addition, a slow accumulation of a colored by-product was observed at elevated temperatures. This was identified as a product of a novel intramolecular carbon to nitrogen 1,4-shift of the methoxycarbonyl... 

The Cope rearrangement and its variants are described very thoroughly in numerous reviews (see, e.g., References 11, 207 and 208). In general, these reactions can be represented by an extremely laconic scheme (equation 152). This system can also include cumulenes24 25 and acetylene fragments209 as well as various substituents and heteroatoms (see Sections IV.D and E). 

The dissociative mechanism of the Cope rearrangement casually mentioned above222 can be illustrated by two examples of Pd-catalyzed reactions. The migration of an allyl group from carbon to carbon in the pyridine system 466 occurs in the presence of a Pd° catalyst236. Refluxing dilute solutions of precursors 466 (R1, R2 = H, Me) in toluene for 7 h or in n -heptane for 24 h gave derivatives 468. The pyridine allyl ether 469 was also... 

In principle, the divinylcyclopropane structure discussed here is incorporated into very well known systems such as bullvalene 547, barbaralane 548 and semibullvalene 549, which very easily undergo a Cope rearrangement. 

Anionic29,314 and thermal315 oxy-Cope rearrangements were reported as steps in the syntheses of various bicyclic systems 586 from divinylcycloalkanes 585 (see Section IV.C.2) (equation 236). The same anionic scheme was applied to prepare ( )-africanol and ( )-isoafricanol (hydroazulene systems)316 as well as ajmaline-related alkaloids (equation 237)317. 

In principle, Cope-type rearrangements can occur in any 1,5-diene system consisting of six carbon and/or heteroatoms (equation 244). However, despite the apparent variety of potential possibilities, few examples of hetero-Cope rearrangements are known up to now. It should be noted that the structures depicted in equation 244 which can generally contain up to six heteroatoms are no longer real dienes. Nevertheless, we will briefly... 

---