Chapter 19 — Quiz

Twenty-five questions on conjugated systems and the Diels-Alder reaction. ∗ marks questions answered in the answer key.

Multiple choice

1.∗ A conjugated diene has: (a) two C=C separated by a sp³ C (b) two C=C separated by one single C-C bond (sp²) (c) a triple bond (d) two C=C separated by an O atom

2.∗ s-cis conformation: (a) the diene's C-C central bond is in cis arrangement; required for Diels-Alder (b) only for alkenes (c) only at low T (d) is forbidden

3.∗ The Diels-Alder reaction is a: (a) [4+2] cycloaddition (4 π from diene + 2 π from dienophile = 6-member ring) (b) [2+2] (c) [3+3] (d) [1+1]

4.∗ The Diels-Alder is: (a) concerted (one-step; no intermediate) (b) stepwise via radical intermediate (c) ionic (with cation intermediate) (d) photochemical only

5.∗ A good dienophile has: (a) electron-donating group on the C=C (b) electron-withdrawing group (lowers LUMO; faster reaction) (c) only methyl groups (d) random

6.∗ The endo rule (kinetic): (a) thermodynamic preference; ignore (b) kinetic preference for endo orientation of EWG (secondary orbital interactions stabilize TS) (c) only with bulky groups (d) only at high T

7.∗ Stereochemistry of Diels-Alder: (a) syn-syn, stereospecific (cis dienophile gives cis product; trans gives trans) (b) anti (c) random mixture (d) photochemical-only

8.∗ [2+2] cycloaddition is: (a) thermally allowed (b) thermally forbidden but photochemically allowed (orbital symmetry mismatch thermally; matched photochemically) (c) stepwise only (d) only in flow chemistry

9.∗ HOMO of diene + LUMO of dienophile: (a) orbital symmetry match → bonding overlap → reaction proceeds (b) no overlap; reaction forbidden (c) repulsive (d) only photochemical

10.∗ 1,4-addition of HBr to 1,3-butadiene: (a) thermodynamic product (high T; equilibrium; more-substituted alkene) (b) kinetic product (low T; closer attack) (c) only at high pressure (d) photochemical only

11.∗ Why is cyclopentadiene more reactive than 1,3-butadiene in Diels-Alder? (a) it's locked in s-cis (always ready); aromatic-like character of the cyclopentadienyl system (b) it's bigger (c) it's less stable (d) random

12.∗ Why is the central C-C bond of 1,3-butadiene shorter than expected (1.47 Å vs 1.54 Å for typical single C-C)? (a) partial double-bond character due to conjugation (b) random (c) only because of substituents (d) inductive effect

13.∗ Maleic anhydride is a great dienophile because: (a) two electron-withdrawing C=O groups lower the LUMO substantially (b) it's bulky (c) it has high melting point (d) random

14.∗ Intramolecular Diels-Alder (IMDA): (a) when diene and dienophile are tethered in one molecule; gives bicyclic product (b) only with special catalysts (c) only at high T (d) only in flow

15.∗ Asymmetric Diels-Alder uses: (a) chiral Lewis acid (e.g., Yamamoto CAB) or chiral organocatalyst (MacMillan imidazolidinone) or chiral auxiliary (Evans oxazolidinone) to give enantioselective product (b) only racemic (c) only thermal (d) only photochemical

16.∗ Hetero-Diels-Alder: (a) diene or dienophile contains a heteroatom (N, O, S); gives heterocyclic ring (b) only on aromatics (c) only photochemical (d) random

17.∗ Retro-Diels-Alder: (a) reversible Diels-Alder; at high T, cyclohexene reverts to diene + dienophile (b) impossible (c) only with light (d) only in solution

18.∗ Diels and Alder shared the Nobel Prize for the Diels-Alder in: (a) 1950 (b) 1928 (c) 1965 (d) 1981

19.∗ Why is the Diels-Alder so widely used in natural product synthesis? (a) builds 6-member ring with up to 4 stereocenters in one step; predictable stereochemistry; concerted; no rearrangement (b) it's only one option (c) it's a hard reaction (d) random

20.∗ Why is biology rarely using Diels-Alder? (a) most biological cycle-forming chemistry uses ionic or radical mechanisms; Diels-Alderases are rare (b) biology uses Diels-Alder constantly (c) it requires high T (d) random

Short answer

21. Sketch the Diels-Alder TS for 1,3-butadiene + maleic anhydride. Identify the cyclic 6-electron arrangement.

22. Why is 1,2-addition kinetic but 1,4-addition thermodynamic for HBr + 1,3-butadiene? Sketch the allylic cation intermediate.

23. Apply the endo rule: cyclopentadiene + maleic anhydride → predict the major product. Show the endo orientation.

24. Compare HOMO and LUMO of a typical diene (1,3-butadiene) and dienophile (ethylene + EWG). Why does the HOMO/LUMO interaction lead to a bonding interaction at both ends of the new bonds?

25. Explain why the Diels-Alder reaction is so widely used in synthesis. Connect to: stereoselectivity, atom economy, ring-building.

Answer key

  1. b — Conjugated diene: 2 C=C separated by sp² single bond.
  2. a — s-cis required for Diels-Alder.
  3. a — [4+2].
  4. a — Concerted.
  5. b — Electron-withdrawing dienophile.
  6. b — Endo kinetic preference.
  7. a — Stereospecific syn.
  8. b — [2+2] thermal forbidden, photo allowed.
  9. a — HOMO-LUMO match.
  10. a — 1,4-addition thermodynamic.
  11. a — Cyclopentadiene locked s-cis.
  12. a — Partial double-bond character.
  13. a — Two EWG lower LUMO.
  14. a — IMDA description.
  15. a — Asymmetric methods.
  16. a — Hetero-Diels-Alder.
  17. a — Retro-Diels-Alder.
  18. a — 1950 Nobel.
  19. a — Multiple stereocenters in one step.
  20. a — Biology rarely uses Diels-Alder.

21. Diels-Alder TS for 1,3-butadiene + maleic anhydride: - 6 atoms arranged in a cyclic 6-member ring (4 from diene + 2 from dienophile). - 6 electrons total: 4 from the diene's π system + 2 from the dienophile's π system. - The diene is in s-cis; the dienophile approaches face-on. - Three pairs of electrons flow simultaneously: - C1 of diene → C1 of dienophile (new σ bond). - C2-C3 of diene π bond stays as new π bond in cyclohexene. - C2 of dienophile → C4 of diene (new σ bond). - The aromatic-like 6-electron TS is thermally allowed (4n+2 = 6 electrons in a closed loop). - The two anhydride C=O groups (electron-withdrawing) lower the LUMO of the dienophile. - Result: the cyclohexene with a fused anhydride ring; maleic and fumaric isomers give different stereo (cis vs trans dicarboxyl groups).

22. HBr + 1,3-butadiene mechanism: - Step 1: H⁺ adds to terminal C1 (the more accessible position; the resulting cation at C2 is allylic, resonance-stabilized). - The allylic cation has resonance structures: positive on C2 (with C3=C4 π) and positive on C4 (with C2=C3 π). The cation is delocalized over C2 and C4. - Step 2: Br⁻ attacks at either C2 (1,2-addition) or C4 (1,4-addition). - At low T: Br⁻ attacks the closer position (C2; faster). 1,2-addition product (3-bromo-1-butene). - At high T: thermodynamic equilibrium prevails. 1,4-addition product (1-bromo-2-butene) has an internal alkene (more substituted; more stable). 1,4-product dominates. The two products interconvert via the allylic cation. At equilibrium, the more-stable 1,4-product wins.

23. Cyclopentadiene + maleic anhydride → endo Diels-Alder product: - Cyclopentadiene (5-member s-cis diene) attacks maleic anhydride (the dienophile) face-on. - The anhydride's two C=O groups (electron-withdrawing) point either endo (toward the diene's π system) or exo (away from it). - Endo orientation: the anhydride C=O π system overlaps with the diene's residual π system (secondary orbital interactions). Stabilizes the TS by ~2-3 kcal/mol. - Exo orientation: less stabilization; less preferred. - Kinetic product: endo norbornene-2,3-dicarboxylic anhydride (the bicyclic 5+6 ring system with anhydride fused, anhydride pointing toward the bridge methylene). - Even though exo is slightly more thermodynamically stable (less strain), kinetic conditions favor endo.

24. HOMO-LUMO interaction in Diels-Alder: - Diene HOMO (ψ₂ of 1,3-butadiene): 4 atomic p orbitals → 4 MOs. ψ₁ all in-phase; ψ₂ has 1 node between C2 and C3. The HOMO is ψ₂; phase: + at C1, + at C2 (both above plane); - at C3, - at C4 (both below plane). Or equivalently, in terms of orbital phases at the terminal carbons (C1 and C4), the HOMO has same sign at both (anti-symmetric about the central node). - Dienophile LUMO (π* of CH₂=CH-EWG): 2 MOs (π and π). The LUMO is π; opposite phases at C1 and C2 (one above, one below).

For productive bonding overlap when the diene approaches the dienophile face-on: - C1 of diene (+) interacts with C1 of dienophile (one phase, say +). Bonding. - C4 of diene (- below the plane, but symmetric with C1) interacts with C2 of dienophile (other phase, say -). Bonding.

Both ends form bonding interactions simultaneously. This is the orbital symmetry match — the foundation of the Diels-Alder being thermally allowed.

In contrast, a [2+2] cycloaddition: alkene HOMO has same phase at both ends; alkene LUMO has opposite phases at both ends. They cannot align productively. Thermally forbidden.

25. Why is Diels-Alder so widely used in synthesis: 1. Builds 6-member ring in one step — the most-common ring size in natural products. 2. Sets up to 4 stereocenters — concerted, stereospecific, predictable. 3. High atom economy — no byproducts; everything goes into the product. 4. No rearrangement — concerted; predictable products. 5. Tolerates many functional groups — not too sensitive to other groups. 6. Wide substrate scope — many dienes and dienophiles available; many can be made by simple synthesis. 7. Stereo-defined — endo rule + cis-syn give predictable stereochemistry. 8. Asymmetric variants — chiral catalysts give enantioselective Diels-Alder.

These features combine to make Diels-Alder a workhorse of natural product synthesis. Many major total syntheses (steroids, taxol, etc.) include Diels-Alder at strategic ring-building steps.