Chapter 39 — Key Takeaways

What you should leave Chapter 39 with

  1. Pericyclic reactions are concerted reactions that proceed through a cyclic transition state with no intermediates, no charges, and no radicals.

  2. Three classes: - Cycloadditions: two π systems combine to form a ring (e.g., Diels-Alder). - Electrocyclic reactions: a conjugated π system closes to a ring (or vice versa). - Sigmatropic rearrangements: a σ bond migrates within a π system.

  3. Woodward-Hoffmann rules: orbital symmetry governs whether a pericyclic reaction is thermally or photochemically allowed.

  4. Aromatic transition state model: a thermally allowed pericyclic reaction has 4n+2 electrons in a closed loop (Hückel-like aromaticity); a forbidden reaction would have 4n electrons (anti-aromatic).

  5. Cycloadditions thermal allowed when total electrons = 4n+2: - [4+2] (Diels-Alder): 4π + 2π = 6 electrons. Allowed. - [2+2]: 4 electrons. Forbidden thermally; allowed photochemically. - [3+2] (1,3-dipolar): 6 electrons. Allowed (e.g., azide + alkyne in click chemistry). - [6+4]: 10 electrons. Allowed thermally.

  6. Electrocyclic reactions: - 4n electrons: thermal conrotatory; photo disrotatory. - 4n+2 electrons: thermal disrotatory; photo conrotatory. - The rotation mode determines stereochemistry.

  7. Specific electrocyclic examples: - Butadiene → cyclobutene (4 π electrons): thermal conrotatory; photo disrotatory. - Hexatriene → cyclohexadiene (6 π electrons): thermal disrotatory; photo conrotatory.

  8. Sigmatropic [m,n] rearrangements: - [3,3] Cope and Claisen: 6 electrons; thermal suprafacial-suprafacial; allowed. - [1,5]-H shift: 6 electrons; thermal suprafacial; allowed. - [1,3]-H shift: 4 electrons; thermal antarafacial; geometrically forbidden. - [1,7]-H shift: 8 electrons; thermal antarafacial; allowed in flexible substrates (e.g., vitamin D).

  9. Cope rearrangement [3,3]: 1,5-hexadiene → 1,5-hexadiene (degenerate but stereospecific). Goes through chair-like TS preferred over boat-like.

  10. Claisen rearrangement [3,3]: allyl vinyl ether → γ,δ-unsaturated carbonyl. Stereospecific; chair-like TS. Many synthesis applications.

  11. Variants of Claisen:

    • Ireland-Claisen: ester enolate version. Stereospecific (Z-enolate → syn; E → anti).
    • Eschenmoser-Claisen: amide variant.
    • Johnson-Claisen: ortho-ester version.
    • Aza-Claisen, thio-Claisen: heteroatom variants.

  12. The Diels-Alder (Ch 19) is the most-used pericyclic reaction in synthesis. Builds 6-member ring + 2 stereocenters in one step. Stereospecific (cis-dienophile → cis-product).

  13. Frontier Molecular Orbital (FMO) theory (Fukui, Nobel 1981): pericyclic reactions are governed by HOMO-LUMO interactions. Soft nucleophiles (high HOMO) + soft electrophiles (low LUMO) favor pericyclic reactions.

  14. Vitamin D photosynthesis: 7-dehydrocholesterol + UVB → previtamin D₃ → vitamin D₃. The photochemical step is a conrotatory electrocyclic ring-opening (6 π electrons); the thermal step is a [1,7]-H sigmatropic shift.

  15. The Nazarov cyclization: 4π electrocyclic closure of a divinyl ketone → cyclopentenone. Lewis acid catalyzed.

  16. The ene reaction: a C-H σ bond + a π bond → new C-C σ bond + new H-X bond. Concerted; pericyclic-like.

  17. Photochemical [2+2]: UV light + two alkenes → cyclobutane. Used in industrial photochemistry (vitamin synthesis).

  18. Pericyclic reactions are stereospecific: the cyclic TS imposes specific geometric constraints; product stereochemistry is determined by reactant geometry + reaction mode.

  19. The 1981 Nobel Prize (Fukui and Hoffmann) recognized the foundational work on pericyclic chemistry. Woodward had passed in 1979.

  20. Pericyclic reactions in synthesis:

    • Diels-Alder: ubiquitous in natural product synthesis.
    • Claisen rearrangement: stereo-controlled C-C bond formation.
    • Cope rearrangement: skeletal rearrangement.
    • Nazarov: cyclopentenone synthesis.
    • Photochemical [2+2]: cyclobutane synthesis (e.g., for vitamin A).
    • Endoperoxide synthesis: artemisinin (Ch 38) uses singlet oxygen [4+2].

Cross-references

  • Chapter 19 — Diels-Alder and conjugated dienes (foundation).
  • Chapter 38 — The art of synthesis (artemisinin endoperoxide via singlet oxygen [4+2]).
  • Chapter 36 — Oxidation/reduction (Sharpless AD/AE; some pericyclic-related).
  • Chapter 40 — Green chemistry and modern catalysis.
  • Appendix C — Reaction summary.
  • Appendix F — Named reactions (Cope, Claisen, Diels-Alder, etc.).

Study tip

For each pericyclic reaction, ask: 1. Class: cycloaddition, electrocyclic, or sigmatropic? 2. Electron count: how many π electrons total? 3. Allowed? Apply 4n+2 rule for thermal; reverse for photo. 4. Stereochemistry: conrotatory or disrotatory? Suprafacial or antarafacial?

If you can answer these for: Diels-Alder, [2+2], Cope, Claisen, electrocyclic of butadiene/hexatriene, [1,5]-H shift, [1,7]-H shift, then you've internalized Chapter 39.

The orbital-symmetry view + the FMO view are complementary. Use whichever makes the problem clearer.