Rearrangements, Cope acceleration

In the presence of a base, the alcohol is converted into the corresponding alkoxide and the rate of rearrangement is accelerated and occurs at room temperature or lower temperature. Thus, the anionic oxy-Cope rearrangement is often performed at or near room temperature and exhibits a considerable tolerance towards functional groups present in the original reactant. 

A <5, -unsaturated carbonyl compound is often the product of an oxy-Cope rearrangement. Oxy-Cope rearrangements are accelerated under strongly basic conditions (KH with or without 18-crown-6). 

Similarly, in the alkoxide variant of the Cope rearrangement, rate accelerations of 10IO-1017 have been observed ... 

The reaction rate of an anionic oxy-Cope rearrangement is accelerated by the presence of an additional unsaturation function on the terminal position. This additional unsaturation function probably stabilizes the transition state and helps the reaction to occur at ease. For example, bicyclic allyl alcohol 74 on rearrangement gives bicyclo-[5.3.1]-undecenone 75 in 88 % yield, while under the same conditions, isomeric alcohol 76 gives 77 in 25 % yield [56]. 

This reaction, called the oxy-Cope rearrangement has proved highly useful in synthesis." The oxy-Cope rearrangement is greatly accelerated (by factors of 10 -10 ) if the alkoxide is used rather than the alcohol.In this case the direct product is the enolate ion, which is hydrolyzed to the ketone. 

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 2-azonia analog of the Cope rearrangement is estimated to be accelerated by 106, relative to the unsubstituted system.270 The product of the rearrangement is an isomeric iminium ion, which is a mild electrophile. In synthetic applications, the reaction is often designed to generate this electrophilic site in a position that can lead to a cyclization by reaction with a nucleophilic site. For example, the presence of a 4-hydroxy substituent generates an enol that can react with the iminiun ion intermediate to form a five-membered ring.271... 

In this domino process, the 1,2-addition is followed by an anion-accelerated oxy-Cope rearrangement and a transannular Dieckmann-type cydization. 

In the synthesis of ( )-palominol and ( )-dolabellatrienone from famesol, Corey and Kania84 employed a dianion accelerated oxy-Cope rearrangement to form the 11,5-trans-fused ring system of the dolabellanes. Diol 112 was treated with potassium hydride in THF to afford a 1 1 mixture of products with iraws-ll,5-fused ring systems, 113 and... 

It was found that Cope rearrangement of the structurally rigid tetracyclic molecule 506 is remarkably accelerated by creating a remote (i.e. non-conjugated) carbenium ion center by an ionization of a ketal group (equation 191)249. The possibility of both classical and non-classical ion participation in this Cope rearrangement was revealed by using MNDO calculations. 

Keywords Aza-Claisen rearrangement 3-Aza-Cope rearrangement Chirality transfer Asymmetric induction Charge acceleration... 

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