Cope rearrangements, solvent effects

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]. 

Oxy-Cope rearrangement. Fujita et al. have examined the effect of various solvents on the course of the oxy-Cope rearrangement of 2-propynols such as 2. N-Methylpsrrrolidone markedly favors formation of 4. HMPT also has the same effect, but in this case it is a result in part of isomerization of 3 to 4. This solvent effect was useful in a synthesis of polyprenyl ketones via an oxy-Cope rearrangement. e -Caprolactam shows a similar solvent effect. 

The Cope rearrangement, like the Claisen rearrangement, is a no mechanism reaction and thus does not involve ionic or radical intermediates. For practical purposes the result is that Cope rearrangements are independent of catalysts and of the nature of the solvent, and that substituent effects are slight. Steric influences, however, are considerable cw-1,2-divinylcyclobutane rearranges to 1,5-cyclooctadiene within a few minutes at 120° ... 

The Claisen rearrangement is generally considered a concerted process. Although a typical pericycHc reaction, such as the Cope rearrangement, is usually insensitive to solvent and polarity of the medium, the rate of the Claisen rearrangement is clearly influenced by these factors. In this section, the effects of these factors are discussed. 

Results using enantiomerically pure substrates demonstrate that a neutral 2-aza-Cope rearrangement occurs with complete transfer of chirality. The effects of solvent and acid catalysis, which convert the process into a cationic rearrangement, have also been studied and DFT calculations predict acceleration of the process under acid catalysis (Scheme 8). 

NMR measurements indicate that the equilibrium constant varies with the polarity of the solvent and temperature. The more polar the solvent, the greater the fraction of sulfoxide at equilibrium which is consistent with the greater dipole moment of the sulfoxide as compared with the sulfenate. Increasing temperature results in a reverse effect, due to the steric hindrance in the sulfoxide which becomes more marked at higher temperatures. These results are the first published evidence for the reversibility of the sulfenate-sulfoxide rearrangement and illustrate the occurrence of the rearrangement unsuccessfully attempted by Cope . 

Explain why the four compounds below rearrange at very different rates and predict the effects of the solvent and the cation. Bear in mind that the oxy-Cope transformation of D is performed in the presence of crown ethers.62... 

QM/MM applications with Cope elimination reactions [663], numerous Diels-Alder cycloadditions and dimerizations, Claisen rearrangements and electro-cyclic ring openings [664-668] indicate that effects coimected with the molecular nature of the solvent influence their reaction rates as well. At first glance this is astmiishing since these reactions are assumed to be rather nonpolar. Again, only the... 

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