Cope reaction/rearrangement

C4-insertions by means of a sigmatropic rearrangement process have been described using either a thermal Cope reaction, anionic Claisen amide enolate and zwitterionic aza-Claisen rearrangements. 

An important improvement in the oxy-Cope reaction was made when it was found that the reaction is strongly catalyzed by base.212 When the C(3) hydroxy group is converted to its alkoxide, the reaction is accelerated by a factor of 1010-1017. These base-catalyzed reactions are called anionic oxy-Cope rearrangements, and their rates depend on the degree of cation coordination at the oxy anion. The reactivity trend is K+ > Na+ > Li+. Catalytic amounts of tetra-rc-butylammonium salts lead to accelerated rates in some cases. This presumably results from the dissociation of less reactive ion pair species promoted by the tetra-rc-butylammonium ion.213... 

The reaction in Entry 5 is a case in which the thermal conditions were preferable to the basic conditions because of the base sensitivity of the product. Entries 6 to 10 show anionic oxy-Cope reactions. Entries 6 and 7 are early examples of the application of the reaction in synthesis. Entries 8 and 9 involve rearrangements of bicyclo[2.2.1]hept-2-en-2-ol derivatives to give cw-fused bicyclo[4.3.0]non-7-en-3-ones. 

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term aza-Claisen should be reserved only for those processes in which a carbon atom in the allyl vinyl ether system has been replaced by nitrogen357.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. 

Conjugated dienes, 11 Conjugation, 11, 368 Conrotation, 345 Coordination polymerisation, 322 Copolymerisation, 322 Cope reaction, 268 Cope rearrangement, 354 Cracking, 112, 305 Cram s rule, 235 Cross-linking, 323... 

Enol formation provides the necessary 1,5-diene for the Cope-like rearrangement. If one provides an enolate anion, the ionic nature of the reaction provides the expected acceleration of rate. 

Besides intermolecular reactions, curved-arrow notation is also useful in indicating bonding changes in intramolecular reactions and rearrangement. For example, Cope-type rearrangements are seen to involve changes in three pahs of bonded electrons. 

A short review of the first 100 years of ketene chemistry covers haloketenes, Wolff (g) rearrangements, stereoselective nucleophilic attack, dimerization, cycloadditions, ketene-Claisen and -Cope reactions, bisketenes, and free radical processes.12 ... 

Quantum chemical studies of cyclizations of enediynes and enyneallenes have been reviewed.180 The intermediates are computationally tractable as a result of the unrestricted broken spin symmetry (UBS) approach using GGA functionals for the description of open-shell biradicals. The intermediacy of biradicals in Cope-type rearrangements, to which the Bergman and Myers-Saito reactions belong, are shown to be predictable using a very simple rule biradicals are likely to be intermediates if they are stabilized either by allyl resonance or by aromaticity. 

The Cope reaction is reversible, but the introduction of an oxygen atom (the oxy-Cope and anionic oxy-Cope rearrangements) results in the formation of an enolate whose stability drives the reaction to completion.308-309 Because the enolate is formed regioselectively, it can be used for further transformations in situ.310-312... 

A new approach to the abe ring system of the pentacyclic C20 diterpenoid alkaloids has been reported by van der Baan and Bickelhaupt.51 For the model system of major interest, (134) was prepared from (133) by reaction with cyano-acetamide. Treatment of (134) with allyl bromide gave almost exclusively C-alkylation, to afford (135). On heating (135) at 100—110°C, a Cope-type rearrangement to (136) was effected. This compound was then N-alkylated with ethyl iodide-DMF, the product being (137). Treatment of (137) with IV-bromosucc-... 

The palladium-catalyzed decarboxylative coupling of allyl 2-(benzo[c(jthiazol-2-yl)acetates 118 provides a facile approach to 2-(but-3-enyl)benzo[c(jthiazoles 122 <07JA4138>. The reaction is initiated by nucleophilic attack of Pd(0) on the allyl ester to give Pd-7t-allyl complex 119, which undergoes nucleophilic attack at the less substituted allylic carbon from the benzothiazole nitrogen to produce 120. Decarboxylative dearomatization leads to intermediate 121, and a subsequent aza-Cope rearrangement driven by rearomatization affords the final product 122 and accounts for the unusual regioselectivity. This appears to be the first report of a tandem allylation/aza-Cope reaction driven by decarboxylative dearomatization/ rearomatization. 

An intramolecular cascade reaction initiated by the addition of an alkenyl radical to a furan was used to synthesize an indene <1998SL1215>. As illustrated in Scheme 31, radical fragmentation in the spiro-dihydrofuran radical 52 provided the intermediate triene 53, which underwent Cope-type rearrangement to form the product. A related reaction with 1-bromocyclohexene that led to unsaturated ketone product was also developed <2003EJ01729>. 

Racemization of the Mannich ba.se may be caused by intrinsic instability " of the optically active final product, or it may occur during the synthesis or the optical resolution. The former case is fiequently observed in the preparation of cyclic derivatives of natural products and concerns Mannich reactions of different types, including the tandem aza-Cope-Mannich rearrangement, which affords more or less extensively ra-cemized products starting from optically active materials. -" -" - This finding is explained on the basis of the equilibrium involved in the 3,3-reanangement leading to ketones 201 (Fig. 72), key intermediates for the synthesis of alkaloids. 

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