Pericyclic Reactions: Cycloadditions and More

• Pericyclic reactions are concerted reactions that proceed through a cyclic transition state
• They involve the reorganization of sigma and pi bonds
• No intermediates are formed

Key Features

• Concerted: All bond-making and bond-breaking occur in a single step
• Cyclic Transition State: The transition state involves a closed loop of interacting orbitals
• Stereospecific: The stereochemistry of the reactants dictates the stereochemistry of the products
• No Intermediates: Unlike stepwise reactions, pericyclic reactions do not involve the formation of carbocations, carbanions, or radicals

Types of Pericyclic Reactions

• Cycloadditions: Two or more unsaturated molecules combine to form a cyclic adduct
• Electrocyclic Reactions: A single unsaturated molecule forms a cyclic product with a new sigma bond
• Sigmatropic Rearrangements: A sigma bond migrates within a molecule
• Group Transfer Reactions: Involve the transfer of an atom or group from one molecule to another

Cycloadditions

• Two unsaturated molecules combine to form a cyclic product
• Classified by the number of pi electrons in each component (e.g., [4+2], [2+2])
• Diels-Alder reaction is a classic example ([4+2] cycloaddition)

Diels-Alder Reaction

• A [4+2] cycloaddition between a conjugated diene and a dienophile
• Forms a cyclohexene derivative
• Highly stereospecific - syn addition
• The diene must be in the s-cis conformation to react

Stereochemistry of Diels-Alder

• Endo Rule: In the Diels-Alder reaction, the substituent on the dienophile prefers to be oriented endo (towards the diene) in the transition state, maximizing overlap of pi systems
• Retention of Configuration: The stereochemistry of substituents on both the diene and dienophile is retained in the product

Electrocyclic Reactions

• Intramolecular reaction involving the formation of a sigma bond between the ends of a conjugated pi system
• Results in a cyclic product

Conrotatory and Disrotatory

• Conrotatory: The terminal p orbitals rotate in the same direction (both clockwise or both counterclockwise)
• Disrotatory: The terminal p orbitals rotate in opposite directions (one clockwise, one counterclockwise)
• The stereochemical outcome depends on the number of pi electrons in the reactant and whether the reaction is thermally or photochemically driven

Woodward-Hoffmann Rules

• Predict the stereochemical outcome of pericyclic reactions
• Based on the symmetry of the highest occupied molecular orbital (HOMO) of the pi system

Selection Rules for Electrocyclic Reactions

• Thermal:
  • 4n pi electrons: conrotatory
  • 4n+2 pi electrons: disrotatory
• Photochemical:
  • 4n pi electrons: disrotatory
  • 4n+2 pi electrons: conrotatory

Sigmatropic Rearrangements

• Involve the migration of a sigma bond within a molecule
• Classified by the number of atoms over which the sigma bond migrates (e.g., [1,5], [3,3])

Cope Rearrangement

• A [3,3]-sigmatropic rearrangement of a 1,5-diene
• Involves the breaking and forming of sigma bonds at the 1 and 5 positions
• Proceeds through a chair-like transition state

Claisen Rearrangement

• A [3,3]-sigmatropic rearrangement of an allyl vinyl ether
• Involves the migration of an allyl group to the ortho position of a phenol

Selection Rules for Sigmatropic Rearrangements

• Suprafacial: The migrating group remains on the same face of the pi system
• Antarafacial: The migrating group transfers to the opposite face of the pi system
• Thermal:
  • [1,n]-sigmatropic shift, n = 4q+2 (suprafacial) allowed
  • [1,n]-sigmatropic shift, n = 4q (antarafacial) allowed
• Generally, suprafacial migrations are more common due to steric accessibility

Frontier Molecular Orbital (FMO) Theory

• Explains the stereochemical outcomes of pericyclic reactions
• Focuses on the interaction between the HOMO of one component and the LUMO of the other component
• The symmetry of the frontier orbitals dictates whether the reaction is allowed or forbidden

HOMO and LUMO

• HOMO: Highest Occupied Molecular Orbital
• LUMO: Lowest Unoccupied Molecular Orbital
• For a reaction to occur, the HOMO of one component must have the same symmetry as the LUMO of the other component at the reaction site

Thermal vs. Photochemical Conditions

• Thermal conditions: The ground state electronic configuration is involved
• Photochemical conditions: One molecule absorbs light and is promoted to an excited state, changing the symmetry of the frontier orbitals
• Reactions that are thermally forbidden may be photochemically allowed, and vice versa

Symmetry Allowed and Forbidden Reactions

• Symmetry Allowed: The interaction between the HOMO and LUMO is constructive, leading to a stable transition state
• Symmetry Forbidden: The interaction between the HOMO and LUMO is destructive, leading to an unstable transition state
• Symmetry forbidden reactions typically do not occur under normal conditions

Applications of Pericyclic Reactions

• Synthesis of complex molecules
• Polymer chemistry
• Material science
• Total synthesis of natural products

Examples in Synthesis

• Diels-Alder reactions are widely used to create cyclic frameworks
• Electrocyclic reactions are used to control stereochemistry
• Sigmatropic rearrangements are used to introduce new functional groups

Factors Affecting Pericyclic Reactions

• Temperature: Higher temperatures generally favor pericyclic reactions
• Solvent: Nonpolar solvents are often preferred for cycloadditions
• Catalysis: Lewis acids can catalyze Diels-Alder reactions
• Steric Effects: Bulky substituents can influence the stereochemical outcome

Summary of Key Concepts

• Pericyclic reactions are concerted, stereospecific reactions that proceed through cyclic transition states
• The Woodward-Hoffmann rules and FMO theory predict the stereochemical outcomes
• The reactions are classified into cycloadditions, electrocyclic reactions, and sigmatropic rearrangements
• Pericyclic reactions are widely used in organic synthesis for their high degree of control and predictable outcomes

Pericyclic reactions are concerted reactions proceeding via cyclic transition states, involving sigma and pi bond reorganization without intermediates. Key features include being concerted, having cyclic transition states, stereospecificity, and no intermediates. Main types are cycloadditions, electrocyclic reactions, sigmatropic rearrangements, and group transfer reactions.