Rate acceleration Cope rearrangement

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... 

Cope rearrangement of arylazo-t-allylmalononitriles [236] shows rate acceleration by acceptor substituents in the phenyl ring. Again, a more polar transition state favor the reorganization. 

A kinetic study of the Cope rearrangement of 2-(trifluoromethyl)oeta-l.5-diene [(Z)-7] showed no rate acceleration in comparison with the rearrangement of unsubsliluled hexa-1,5-diene. Equilibrium was reached after 7 days at 207 C (K = 3.46 favoring the is-isomer). at which stage no intermediate 4-ethylhcxa-l,5-diene 8 was observed.6 In contrast, a trifluoromethyl group at position 2 does accelerate the Claisen rearrangement (sec Section 5.1.5.2.). 

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. 

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

Substituent effects provide other insights into the nature of the TS for the Cope rearrangement. Conjugated substituents at C(2), C(3), C(4), or C(5) accelerate the reaction. Donor substituents at C(2) and C(3) have an accelerating effect. The net effect on the reaction rate of any substituent is determined by the relative stabilization of the TS and ground state. The effect of substituents on the stabilization of the TS can be analyzed by considering their effect on two interacting allyl systems. We consider the case of phenyl substituents in detail. 

Aza-Cope rearrangement of Enammonium cations to give y, (5-unsaturated aldehyde products, via formation of imminium cations first and subsequent hydrolysis (Scheme 5.16), and acid hydrolysis of orthoformates in basic solution (Scheme 5.17). It is worth noting that in both reactions the catalytic rate is enhanced up to 1000-fold for the former and up to 890-fold for the latter. It is believed that due to reaction space restriction inside the capsule 5.32, as well as preorganization of the substrates into reactive conformations, the catalytic reactions described above are accelerated. 

If a significant fraction of this kind of stabilization of a radical is felt in the transition state of the oxy-Cope rearrangement, the rate acceleration is understandable. 

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]. 

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