Rearrangements, Cope reverse

BF3 reacts with the carbonyl group to form an ate complex of A, whose powerful acceptor properties promote the Cope rearrangement. The reverse reaction does not occur because the ate complex of B cannot influence the 3 or 4 position. 

The position of the Cope equilibrium in 3,4 rearrangements of 1,2-divinylcycloalkanes largely depends on the ring size. In the case of 1,2-divinylcyclopropanes and cyclobutanes, the equilibrium lies on the side of the enlarged rings. For 1,2-divinylcyclopentanes, cyclohexanes, and cycloheptanes, the equilibrium of the Cope rearrangement is reversed, but use of the irreversible... 

Oxy-Cope rearrangement Cope-rearrangement reaction is reversible and gives equilibrium mixture of two 1, 5-dienes which are richer in thermodynamically more stable isomer. But, reaction of 3-hydroxy-l, 5-diene can not be reversed, because 3-hydroxy-l, 5-diene tautomerises to carbonyl compound as given below. This rearrangement is known as Oxy-cope rearrangement. 

Starting from a 3-hydroxy-1,5-diene 8, the rearrangement is not reversible, because the Cope product 9 tautomerizes to an aldehyde or ketone 10, and is thereby removed from equilibrium ... 

As a continuation to the studies by Darwish and Braverman on the [2,3]-sigmatropic rearrangement of allylic sulfinates to sulfones, and in view of its remarkable facility and stereospecificity (see Chapter 13), Braverman and Stabinsky investigated the predictable analogous rearrangement of allylic sulfenates to sulfoxides, namely the reverse rearrangement of that attempted by Cope and coworkers . These authors initiated their studies by the preparation of the claimed allyl trichloromethanesulfenate using the method of Sosnovsky . This method involves the reaction between trichloro-methanesulfenyl chloride and allyl alcohol in ether at 0 °C, in the presence of pyridine (equation 6). 

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 . 

Entry 2 illustrates the reversibility of the Cope rearrangement. In this case, the equilibrium is closely balanced with the reactant benefiting from a more-substituted double bond, whereas the product is stabilized by conjugation. The reaction in Entry 3 involves a cz s-divinylcyclopropane and proceeds at much lower temperature that the previous examples. The reaction was used in the preparation of an intermediate for the synthesis of pseudoguiane-type natural products. 

Nucleophilic addition of primary o.-R -allylamine to nitrone followed by a reverse Cope cyclization and Meisenheimer rearrangement gives the oxadiazi-nanes (426a-h) (Scheme 2.198). These reactions have found use for the preparation of oxadiazines, vicinal aminohydroxylamines, and diamines the latter are of particular interest as chiral ligands (683, 684). 

Dihydronaphthalenes are remarkable substrates for the combined C-H activation/Cope rearrangement, but under certain circumstances, further cascade reactions can occur. This was seen in the Rh -DOSP -catalyzed reaction of vinyldiazoacetate 26 with dihydronaphthalene 25 (Equation (35)).96 In this case, the isolated product was the formal C-H insertion product. The reaction proceeded through a combined C-H activation/Cope rearrangement to form 27, followed by the reverse Cope rearrangement. As both steps were highly stereoselective, the formal C-H insertion product 28 was produced with very high stereoselectivity (>98% de, 99.6% ee).96... 

The reaction with the siloxy derivative 29 is an interesting example because the product 30 is a 1,5-dicarbonyl derivative (Equation (36)).96 1,5-Dicarbonyls are classically prepared by a Michael addition, but the synthesis of 30 by a Michael addition is not possible because it would require addition to the keto form of 1-naphthol. The acetoxy derivative 31 resulted in a different outcome, leading to the direct synthesis of the naphthalene derivative 32 (Equation (37)).96 In this case, the combined C-H activation/Cope rearrangement intermediate was aromatized by elimination of acetic acid before undergoing a reverse Cope rearrangement. 

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... 

Various mechanisms are discussed for the migration of a benzyl group including, e.g., a two-stage Cope or reverse Claisen rearrangement as well as a preference of direct [l,5]-shift over successive Wagner-Meerwein migrations (equation 115)173. 

Allylthiols376 and unsaturated lithio sulfones377 have been found to react as nucleophiles with nitrones to yield intermediate hydroxylamines which undergo reverse-Cope cyclization to provide 1,3-thiazolidine N-oxides and pyrrolidine A-oxides, respectively. In the case of derivatives of C-phenyl nitrone (321 R2 = Ph), thermolysis was found to result in smooth Meisenheimer rearrangement leading to 1,5,2-oxathiazinane (322) (see Scheme 76). 

The mechanism involves 2-oxonia-Cope rearrangements via (Z)-oxocarbenium ion intermediates, as shown in Scheme 7. It has been shown that racemization can be suppressed by conditions or structural features which slow the Cope rearrangement in either forward or reverse directions, since the [3,3]-sigmatropic rearrangement must occur many times before reaction via the less favoured (Z)-oxocarbenium ion becomes important.20... 

The intramolecular nitrone-alkene cycloaddition reaction of monocyclic 2-azetidinone-tethered alkenyl(alkynyl) aldehydes 211, 214, and 216 with Ar-aIkylhydroxylamincs has been developed as an efficient route to prepare carbacepham derivatives 212, 215, and 217, respectively (Scheme 40). Bridged cycloadducts 212 were further transformed into l-amino-3-hydroxy carbacephams 213 by treatment with Zn in aqueous acetic acid at 75 °C. The aziridine carbaldehyde 217 may arise from thermal sigmatropic rearrangement. However, formation of compound 215 should be explained as the result of a formal reverse-Cope elimination reaction of the intermediate ct-hydroxy-hydroxylamine C1999TL5391, 2000TL1647, 2005EJ01680>. 

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