organic reaction mechanisms: cope reaction

Theory and Defination :

The Cope rearrangement is an organic reaction where a 1,5-diene, under thermal conditions, is converted to another 1,5-diene structural isomer. This reaction belongs to a class of reactions termed "sigma tropic rearrangements" and it is a concerted process where bonds are forming and breaking at the same time. When substituents are present in the initial diene starting material, the stereochemistry of this reaction can be predicted by drawing the molecule in a chair-like conformation. Placing the substituents in the equatorial position minimizes the steric interactions and leads to the major product. The Cope rearrangement is an equilibrium reaction and the equilibrium position is determined by the overall stability of the starting material and product.

General Reaction :

The Cope rearrangement is an extensively studied organic reaction involving the [3,3]-sigmatropic rearrangement of 1,5-dienes.It was developed by Arthur C. Cope. For example 3-methyl-1,5-hexadiene heated to 300°C yields 1,5-heptadiene.

Mechanism:

The Cope rearrangement is a pericyclic reaction, as shown below

Transition state is formed when heat is applied.

The Oxy-Cope Rearrangement Mechanism is shown below

Examples and Application :

The rearrangement is widely used in organic synthesis. It is symmetry-allowed when it is suprafacial on all components. The transition state of the molecule passes through a boat or chair like transition state. An example of the Cope rearrangement is the expansion of a cyclobutane ring to a 1,5-cyclooctadiene ring:
In this case, the reaction must pass through the boat transition state to produce the two cis double bonds. A trans double bond in the ring would be too strained. The reaction occurs under thermal conditions. The driving force of the reaction is the loss of strain from the cyclobutane ring.

Oxy-Cope rearrangement:

In the Oxy-Cope rearrangement a hydroxyl group is added at C3 forming an enol or enone after Keto-enol tautomerism of the intermediate enol.

for instance in this reaction:

In 1975, Evans and Golob showed that deprotonation of oxy-Cope substrates to form the corresponding alkali metal alkoxides resulted in rate accelerations of 10¹⁰ to 10¹⁷ for the oxy-Cope rearrangement. Typically potassium hydride and 18-crown-6 are employed in order to generate a fully dissociated potassium alkoxid.

It is noteworthy that the anion-accelerated oxy-Cope reaction can proceed with high efficiency even in systems that do not permit good orbital overlap, as seen in this example from Schreiber's synthesis periplanone B

Cope Elimination reaction

Theory and Defination :

This reaction is developed by Arthur C. Cope.
The cope elimination is a one-step process of oxidation of tertiary amine with a peroxide forms an N-oxide that undergoes an intramolecular deprotonation with syn stereoselectivity upon heating. This reaction is known as cope elimination. Because the cope elimination involves a cyclic transition state, it occurs with stereo chemistry.
Cope elimination generally gives the same orientation as Hoffman elimination resulting in less substituted alkene. This elimination reaction is also called cope reaction.

General Reaction :

Mechanism :

Cope reaction is believed to take place through a cyclic transition state as depicted below.

The formed transition state behaves as :

The direction of the cope elimination is governed almost entirely by the number of hydrogen atoms at the various beta position. Therefore, there is no preference for the formation of the least substituted alkenes unlike in the Hoffman elimination reaction.It is to be noted that cope elimination is cis and needs lower temperatures than the pyrolysis of quatenary ammonium hydroxides.

Examples and Application :

The synthetic utility of the cope elimination is comparable to the Hofmann elimination of quatenary ammonium hydroxides, but takes place at lower temperatures.
The Cope elimination is almost free of side reactions due to the intramolecular nature of the elimination. However, in certain cases, the product alkene may isomerize to the more stable conjugated system, and allyl-or benzyl migration is sometimes observed to give O-allyl or benzyl substituted hydroxyamines. Cyclic amine oxides can also be pyrolysed but with 6-membered rings the reaction is usually low-yielding or does not occur.

1) The amine is oxidized with hydrogen peroxide to give oxide which on Heating gives methylenecyclohexane and N,N-dimethylhydroxylamine through an intramolecular elimination reaction.