Cycloaddition

Definition

Cycloaddition is a fundamental organic chemistry reaction in which two or more unsaturated molecules, or parts of the same molecule, combine to form a cyclic adduct. This process is a powerful tool for the synthesis of a wide range of carbocyclic and heterocyclic compounds, and it is particularly important in the context of alkene oxidation, carbene addition, the Diels-Alder reaction, and various thermal electrocyclic and cycloaddition reactions.

5 Must Know Facts For Your Next Test

1. Cycloadditions are classified based on the number of $\pi$-bonds involved in the reaction, such as [2+2] cycloadditions and [4+2] cycloadditions (the Diels-Alder reaction).
2. The stereochemistry of cycloaddition reactions is typically preserved, with the relative stereochemistry of the reactants being transferred to the cyclic product.
3. Cycloadditions can be thermally induced (thermal cycloadditions) or photochemically induced (photochemical cycloadditions), and the stereochemical outcomes may differ between the two.
4. Benzyne, a highly reactive intermediate in organic synthesis, undergoes cycloaddition reactions with various nucleophiles to form substituted benzene derivatives.
5. The stereochemistry of cycloaddition reactions, including the Diels-Alder reaction, is a key consideration in understanding and predicting the outcomes of these transformations.

Review Questions

• Explain the role of cycloaddition reactions in the oxidation of alkenes to form carbonyl compounds.
  • The oxidation of alkenes to form carbonyl compounds, as described in Section 8.8, can involve a cycloaddition step. Specifically, the reaction of an alkene with an oxidizing agent, such as osmium tetroxide (OsO4) followed by cleavage, proceeds through a cyclic intermediate known as an osmate ester. This cycloaddition step is a crucial part of the mechanism, as it allows for the selective oxidation of the alkene to form the desired carbonyl product.
• Describe how cycloaddition reactions are used in the synthesis of cyclopropanes from alkenes and carbenes, as discussed in Section 8.9.
  • The addition of carbenes to alkenes, as covered in Section 8.9, is a cycloaddition reaction that leads to the formation of cyclopropanes. In this process, the carbene, a highly reactive species, undergoes a [2+1] cycloaddition with the $\pi$-bond of the alkene, resulting in the creation of a new three-membered ring. The stereochemistry of the alkene is typically preserved in the cyclopropane product, making this an important synthetic transformation for the construction of small-ring carbocycles.
• Analyze the role of cycloaddition reactions in the Diels-Alder reaction, as discussed in Sections 14.4 and 14.5, and explain how the stereochemistry of the reactants is reflected in the cyclic adduct.
  • The Diels-Alder reaction, covered in Sections 14.4 and 14.5, is a prototypical example of a [4+2] cycloaddition. In this reaction, a conjugated diene (the 4$\pi$-component) reacts with a dienophile (the 2$\pi$-component) to form a substituted cyclohexene ring. The stereochemistry of the reactants is preserved in the cyclic adduct, with the relative positions of the substituents on the newly formed ring reflecting the initial orientation of the reacting partners. This predictable stereochemical outcome is a key feature of the Diels-Alder reaction and is crucial for its widespread use in organic synthesis.

Related terms

Concerted Reaction: A cycloaddition reaction that proceeds in a single step, without the formation of any discrete intermediates.

Frontier Molecular Orbital Theory: A theoretical framework used to explain and predict the outcomes of cycloaddition reactions based on the interactions between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) of the reactants.

Regiochemistry: The selectivity of a cycloaddition reaction in terms of the relative positions of the atoms in the newly formed ring.