Overview
This lecture introduces paracyclic reactions, focusing on the Diels-Alder cycloaddition, molecular orbital interactions, and the effects of UV light on DNA and biological processes.
DNA Damage and Paracyclic Reactions
- UV light can induce reactions between adjacent pyrimidines (thymine and cytosine) in DNA, forming pyrimidine dimers.
- Pyrimidine dimers can disrupt DNA replication and cause mutations or cancer.
- The body repairs this damage and sunscreens help prevent it.
Paracyclic Reactions: General Features
- Paracyclic reactions have cyclic transition states and occur via concerted mechanisms (no intermediates).
- Bonds break and form simultaneously in one step.
The Diels-Alder Reaction
- The Diels-Alder reaction joins a conjugated diene and a dienophile (alkene or alkyne) to form two new carbon-carbon bonds.
- This reaction is highly stereoselective and regioselective.
- The mechanism is concerted and can be visualized via arrow-pushing and molecular orbitals.
Molecular Orbitals in Cycloaddition
- The diene's highest occupied molecular orbital (HOMO) interacts with the dienophile's lowest unoccupied molecular orbital (LUMO).
- Efficient reactions require the reactant orbitals to be similar in energy and in phase (superfacial).
Reactivity Factors
- Electron-donating groups on the diene raise its HOMO energy, promoting reactivity.
- Electron-withdrawing groups on the dienophile lower its LUMO energy, making reactions easier.
- The diene must adopt the S-cis conformation to react; S-trans is unreactive.
Stereochemistry and Regiochemistry
- Z (cis) dienophiles produce cis products; E (trans) produce trans.
- Product orientation (endo vs. exo) is influenced by orbital interactions, with endo favored.
- Group placement on diene/dienophile dictates product regiochemistry, similar to ortho/para on benzene.
Other Paracyclic Reactions and Photochemistry
- Cycloadditions are classified by the number of carbons in the reacting pi systems, e.g., 4+2 (Diels-Alder), 2+2 (pyrimidine dimer formation).
- 2+2 cycloadditions need UV light (photochemical, allowed); thermal conditions are forbidden.
- Sunlight drives other biological paracyclic reactions, such as vitamin D3 synthesis (electrocyclic ring opening, sigmatropic rearrangement).
Key Terms & Definitions
- Paracyclic reaction — concerted, cyclic transition-state reaction with simultaneous bond breaking/forming.
- Diene — compound with two adjacent double bonds.
- Dienophile — compound (alkene or alkyne) that reacts with a diene in a Diels-Alder reaction.
- HOMO — highest occupied molecular orbital.
- LUMO — lowest unoccupied molecular orbital.
- Superfacial — orbital overlap occurs on the same face.
- Endo product — stereoisomer where substituents point toward the more crowded side of a bicyclic system.
- Sigmatropic rearrangement — a paracyclic reaction where sigma and pi bonds are reorganized.
Action Items / Next Steps
- Review episode 38 for electron-donating/withdrawing group identification.
- Watch episode 41 for more on UV-Vis and HOMO/LUMO concepts.
- Prepare for the next lecture on nucleophilic carbon chemistry (enols and enolates).