Cope rearrangements synthetic utility

Aliphatic 3-aza-4-oxa-Cope rearrangement of ester-amide dienolates increases the synthetic utility of anionic [3,3]-sigmatropic rearrangement initiated by N—O bond cleavage. Treatment of the enehydroxylamine 94 with KHMDS in the presence of TMSCl at —80°C provided a mixture of iV,0-disilylated 95 and 0,0-disilylated 96 derivatives (equation 30). Both of these would, on [3,3]-sigmatropic rearrangement, provide the corresponding silyl ethers 97 and 98, from which 99 and 100 are obtained on workup. 

Although the anionic oxy-Cope rearrangement of 47 served admirably as a means for accessing 50 and 52, the utility of the major tetracyclic product was not viewed with optimism. We identified a variety of options for central bond cleavage therein, but the steps needed to accomplish this chemistry were certain to result in appreciable lengthening of the synthetic undertaking. For these reasons, we turned our attention instead to the deployment of 45 as the precursor to the nucleophile of choice. 

The synthetic utility of this process can be seen by evaluating the examples in Table 2. For example, because the cyclopropane serves as a pseudo alkene and because the [1.5] shift requires a six-memb ed transition state, it relates conceptually to the Cope and Claisen rearrangements. The 7,8-unsaturated carbonyl compounds in Table 2 are those that would otherwise be obtained via Claisen or orthoester Claisen rearrangements, which are normally effected under strongly acidic or strongly basic conditions (Scheme 3). 

A detailed reexamination of the thermal rearrangement of 1-methyl-imidazole originally reported by Wallach has been extended to encompass a wide range of 1-substituted imidazoles. The reaction appears to be of potential synthetic utility since it leads easily to 2-alkyl- and 2-arylimidazoles. It is an irreversible reaction, uncatalyzed, intramolecular, and does not involve radicals [l,5]-sigmatropic shifts, as shown in Scheme 40, are probably implicated. The major product is the 2-substituted imidazole (134), but small amounts of the 4- (or 5-) isomer (135) are also formed. A 1-allyl substituent migrates with equal facility to both 2- and 4(or 5)-positions, suggesting that a Cope-type rearrangement may also be involved for this substituent. ... 

An interesting synthetic target related to triptindane is the tris(naph-tho)[3.3.3]propellane 86 (Schemes 16 and 17). Alder et al. [84] reported on first attempts to construct this two-fold triptindane bearing a highly strained C - C bond. Cyclodehydration of acenaphthenediol 85, prepared previously from acenaphthene quinone (84) [85], or the corresponding pinacolone formed as an intermediate in the acidic medium, did not occur in the desired way (Scheme 16). Attempts to utilize the corresponding bis(dihydro) derivative (i.e. the diol derived from 87) resulted in the formation of the C2-symmetrical polycycle 88, possibly by di-oxy Cope rearrangement followed by a criss-cross [2 + 2] cycloaddition [84]. 

The K-alkoxide of the startg. m. prepared with KH in anhydrous tetrahydrofuran heated several min. at 66° product. Y 98%. - Both the increased yield and lower reaction temp, in this anionic oxy-Cope process should improve the synthetic utility of these and related rearrangements. F. e. s. D. A. Evans and A. M. Golob, Am. Soc. 97, 4765 (1975). 

As a reversible process, the synthetic utility of the 2-aza-Cope rearrangement is limited by the fact that, with rare exception, neither side of the equilibrium is favored by a si ficant amount. In spite of this, it has become a valuable S5mthetic tool. Many of the methods developed drive the equilibrium by either trapping " or cleaving one isomer preferentially., 260-26 recent report utilizes the trapping of a more... 

In recent years, the synthetic utility of the cyclopropyl-Cope rearrangement has expanded exponentially as a result of new chiral organometallic catalysts which allow for the efficient, stereoselective formation of the required cw-divinylcyclopropanes. " One of the leaders in this area is Davies, who has repeatedly demonstrated the successful tandem cyclopropanation/Cope rearrangement between vinyldiazoacetates and dienes for the synthesis of functionalized seven-membered rings. 

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