Carbon Cope rearrangements

We used the all-carbon Cope rearrangement 29 to introduce this section but now we want to feature the more useful Claisen rearrangements.14 The aliphatic Claisen 54 works for most substituents because an alkene is lost and a much more stable carbonyl group is formed 55. It doesn t matter whether we have an aldehyde (X = H), a ketone, (X = R), an acid (X — OH), an ester (X = OR) or an amide (X = NR2), the reaction works well. The original Claisen rearrangement was the aromatic version 56 that gives an unstable non-aromatic intermediate 57 that quickly loses a proton to restore the aromatic ring and the product is a phenol 58. 

Two common six-membered rearrangements of 1,5-dienes have Y as either oxygen (Claisen rearrangement) or carbon (Cope rearrangement). Both are reversible and favor the more stable product. The preceding example problem demonstrated that they were thermally allowed An+2 suprafacial retention processes. As in the Cope example problem above, the transition state for the reaction commonly resembles the chair conformation of cyclohexane. Figure 12.29 shows a biochemical example of the Claisen rearrangement. 

The most intriguing hydrocarbon of this molecular formula is named buUvalene, which is found in the mixture of products of the reaction given above. G. SchrOder (1963, 1964, 1967) synthesized it by a thermal dimerization presumably via diradicais of cyciooctatetraene and the photolytical cleavage of a benzene molecule from this dimer. The carbon-carbon bonds of buUvalene fluctuate extremely fast by thermal Cope rearrangements. 101/3 = 1,209,6(X) different combinations of the carbon atoms are possible. 

The most important sigmatropic rearrangements from the synthetic point of view are the [3,3] processes involving carbon-carbon bonds. The thermal rearrangement of 1,5-dienes by [3,3] sigmatropy is called the Cope rearrangement. The reaction establishes equilibrium between the two 1,5-dienes and proceeds in the thermodynamically favored direction. The conversion of 24 to 25 provides an example ... 

Migration from nitrogen to carbon is observed also in aza-Cope rearrangement [76] Ring expansion occurs in thermal rearrangement of azindine denvauves [77] (equation 17)... 

Step through the sequence of stmctures depicting Cope rearrangement of 1,5-hexadiene. Plot energy (vertical axis) vs. the length of either the carbon-carbon bond being formed or that being broken (horizontal axis). Locate the transition state. Measure all CC bond distances at the transition state, and draw a structural formula for it... 

Another compound for which degenerate Cope rearrangements result in equivalence for all the carbons is hypostrophene W1). In the case of the compound barbaralane (108) (bullvalene in which one CH=CH has been replaced by a CH2) ... 

Among the best known examples, involving a carbon moiety, is the shift from one carbon atom to another observed in the Cope rearrangement of 1,5-dienes (49— 50 not to be confused with the... 

The use of a carbene as the one-carbon component provides an alternative and efficient entry into the [4 + 2+1]-reaction manifold. Montgomery and Ni have developed a nickel-catalyzed process where the carbene is generated from trimethylsilyldiazomethane (Scheme 45).135 It is not known, however, if the seven-membered ring forms via a Cope rearrangement of a divinylcylopropane or if the metal is intimately involved in the step that leads directly to... 

In response to the prediction by Dewar et al. (1971) that the azasemibull-valenes [100] and [101] should be neutral homoaromatics, the Mullen group prepared the diazasemibullvalene [102]. Although the Cope rearrangement of [102] is more facile than in the all-carbon analogue (replace N with CH in... 

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 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, 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... 

There is no unity of opinion in the literature concerning a classification, i.e, whether to call these transformations aza-Claisen or aza-Cope rearrangements. It is accepted that the term aza-Claisen should be reserved only for those processes in which a carbon atom in the allyl vinyl ether system has been replaced by nitrogen357. Three different types of aliphatic 3-aza-Cope reactions which were studied theoretically are the rearrangements of 3-aza-l,5-hexadienes (610, equation 262), 3-azonia-l,5-hexadienes (611, equation 263) and 3-aza-l,2,5-hexatrienes (612, equation 264) (the latter is a ketenimine rearrangement )357. 

With respect to the above-mentioned unsaturated carbonyl compounds with a double bond and a carbonyl group separated by three carbon atoms (14), it can be stated here that they may be disconnected to an alkyl vinyl ketone and an allylic anion (Scheme 7.5), through an oxy-Cope rearrangement (C/. Scheme 5.22). 

The 3-aza-4-oxa-Cope rearrangement in which the weak N—O bond is cleaved and a new carbon-carbon bond is generated (equation 6) is the most frequently used hydrox-ylamine rearrangement. Low temperature and moderated reaction conditions make this rearrangement an important synthetic tool. 

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