Chapter 10. Conjugation Chemistry

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3. 4+2 Cycloaddition Reaction (Diels-Alder Reaction)

1. Conjugation

⑴ State where p orbitals overlap continuously with three or more orbitals

Figure 1. Example of Conjugation: C₃H₅

⑵ Conjugated molecules have electrons located in p orbitals on each atom, delocalizing electrons and leading to greater stability compared to unconjugated molecules.

① According to Particle in a Box in quantum mechanics, delocalization (conjugation) lowers the energy of particles.

⑶ Conjugated compounds can interact with low-energy light, absorbing light in the ultraviolet or visible range

① Principle of UV-Vis spectrum

⑷ Structure and Stability (e.g., Diene)

① Bond lengths of conjugated dienes

○ C₂H₄ double bond length: 134 pm

○ CH₃-CH₃ single bond length: 153 pm

○ CH₂CHCHCH₂ double bond length: 134 pm

○ CH₂CHCHCH₂ single bond length: 148 pm < 153 pm

② Stability through hybridization

○ CH₃-CH₃: Each carbon has 25% s-character from sp3 hybridization, leading to larger bond distance → less stable

○ CH₂CHCHCH₂: Middle carbons have 33% s-character from sp2 hybridization, leading to shorter bond distance → more stable

③ Stability through resonance stabilization

Figure 2. Resonance Stabilization of Diene

④ Stability confirmation through molecular orbital functions: All electron pairs are in bonding orbitals

Figure 3. Molecular Orbital Functions of Diene

⑸ Stability Confirmation: Hydrogenation enthalpy, heat of reaction per carbon

⑹ Chemistry of Allylic Positions

⑺ Electrophilic Addition Reactions of Conjugated Alkenes

2. 2+2 Cycloaddition Reaction

⑴ hν Condition

Figure 4. 2+2 Cycloaddition Reaction

3. 4+2 Cycloaddition Reaction (Diels-Alder Reaction)

⑴ Definition: Ring-forming addition reaction between nucleophilic dienes and electrophilic dienophiles

Figure 5. Overview of Diels-Alder Reaction

① Favorable enthalpy-wise but unfavorable entropy-wise, allowing the reaction to occur

② Conditions: Δ, BF₃ (Lewis acid catalyst)

○ Lewis Acid Catalyst: Increases electrophilic strength of the dienophile, enhancing reaction rate

⑵ Characteristics

① Woodward-Hoffmann rule: Occurs only under thermal conditions and does not react under photochemical conditions.

② Frontier molecular orbital theory: The electrons from the HOMO of the diene move to the LUMO of the dienophile, resulting in a reaction.

③ However, cyclization can also occur between the LUMO of the diene and the HOMO of the dienophile.

④ The reaction is highly reactive, proceeding easily even at temperatures as low as 40°C.

⑤ At very high temperatures, the reverse reaction may also occur.

⑶ Diene: Corresponds to the HOMO in the Diels-Alder reaction

① Factor 1. The reaction is faster with a higher proportion of the s-cis isomer.

○ Reason: The s-trans isomer does not undergo the reaction due to the increased ring strain in the final product, a six-membered ring.

○ However, it is important to consider that the s-cis form is 2-3 kcal/mol less stable than the s-trans form.

○ Example: Cyclopentadiene is fixed in the s-cis form and is therefore very reactive.

② Factor 2. Diels-Alder reactions are also difficult in structures with diynes.

○ Reason: Because the four-membered ring products are unstable.

③ Factor 3. As a nucleophile, the reaction rate is faster when there are more electron-donating groups (EDGs) and fewer electron-withdrawing groups (EWGs) because the electron density is higher.

④ Factor 4. In the s-_cis_ conformation, a diene without steric hindrance reacts faster than a diene with steric hindrance.

○ For this reason, five-membered rings are highly reactive, whereas six-membered rings react more slowly and reactions in seven-membered rings are almost non-existent.

Figure 6. Comparison of the reaction rates of 2,4-hexadiene in the Diels-Alder reaction

⑷ Dienophile: Corresponds to LUMO in Diels-Alder Reaction

① Factor 1. As an electrophile, greater electron-withdrawing groups (EWG) and fewer electron-donating groups (EDG) lead to lower electron density and faster reaction rate

⑸ Stereoselective Reaction: Comparison of endo and exo

Figure 7. Stereoselective Reaction in Diels-Alder Reaction

① endo and exo products are partial diastereomers

○ endo arrangement: Substituents are oriented toward the larger ring direction based on the bridgehead carbon

○ exo arrangement: Substituents are oriented toward the smaller ring direction based on the bridgehead carbon

○ In the above diagram, the endo arrangement is closer to the five-membered ring, and the exo arrangement is closer to the six-membered ring.

○ Memorization tip: Place the diene above and the dienophile below. The pathway that results in the intermediate with the maximum overlap between the two leads to the endo product, while the pathway with the minimum overlap leads to the exo product.

○ When endo Diels-Alder reaction goes, strongest EDG on diene at the top flips up.

○ When endo Diels-Alder reaction goes, strongest EWG on dienophile at the bottom flips down.

② Reaction rate-wise, endo product is dominant due to the stability difference of the transition state

Figure 8. Difference in the number of orbital interaction between exo and endo

○ At low temperatures (25 ℃), endo product is the major product

○ exo transition state: Only primary interactions exist

○ endo transition state: Both primary and secondary interactions exist

○ Even in non-bicyclic compounds, endo product is predominant

③ Thermodynamically, exo product is predominant

○ Reason: Less steric hindrance with substituents in the smaller ring direction

○ At high temperatures (90 ℃), exo product is the major product

○ Reason: Because the kinetically controlled product can revert back to the reactants through a reverse reaction.

④ Exception

○ When the dienophile is an alkyne, the substituent orientation of the product conforms to the general alkene bonding positions, not endo or exo

⑹ Position-Selective Reaction (ortho-para rule)

① Definition: A rule stating that the EDG of the diene and the EWG of the dienophile in the final product should be oriented in the ortho or para direction

② ortho orientation reaction

Figure 9. Reaction with ortho Orientation

Figure 10. Understanding of diene and dienophile in ortho orientation

③ para orientation reaction

Figure 11. Reaction with para Orientation

Figure 12. Understanding of diene and dienophile in para orientation

④ Reason: Favorable overlap of p orbitals between carbon with partial negative charge due to EDG and carbon with partial positive charge due to EWG

⑺ Application 1. 1,3-dipolar cycloaddition

① Reaction similar to Diels-Alder reaction

② Common when N₂O-R, N₃-R, etc., are reactants

Figure 13. 1,3-dipolar cycloaddition

4. Other Cycloaddition Reactions

⑴ Woodward-Hoffmann Rule

① (Formula) When the number of π electrons is 4n: under Δ conditions, conrotatory; under hν conditions, disrotatory.

② (Formula) When the number of π electrons is 4n + 2: under Δ conditions, disrotatory; under hν conditions, conrotatory.

Figure 14. Woodward-Hoffmann rule when the number of π electrons is 6

③ Memorization tip: The Woodward-Hoffmann rule also applies to Diels-Alder reactions with the condition that the number of π electrons is 4n + 2 under Δ conditions.