Chapter 19 — Exercises

Forty-five problems on conjugated systems and the Diels-Alder reaction. Drawing required wherever a structure or mechanism is asked for. ∗ marks problems with full worked solutions in Appendix Answers to Selected Exercises.

Section A — Conjugated dienes

19.1∗ (routine) Draw 1,3-butadiene. Identify: (a) the conjugated π system. (b) the s-cis vs s-trans conformations. (c) why the central C-C bond is shorter than expected.

19.2 (routine) Compare 1,3-butadiene (conjugated) with 1,4-pentadiene (non-conjugated, isolated). Which is more stable? By how much (rough)?

19.3∗ (routine) Cyclopentadiene is locked in s-cis. Why is this important for Diels-Alder?

19.4 (moderate) 1,3,5-Hexatriene has 6 π electrons in 3 conjugated C=C bonds. Sketch its 6 π MOs and identify HOMO and LUMO.

19.5 (challenge) Why do conjugated dienes show characteristic UV absorption around 215-235 nm? Compare to isolated alkenes (~190 nm).

Section B — 1,2- vs 1,4-addition

19.6∗ (routine) Predict the major product of: (a) 1,3-butadiene + HBr at -80 °C → ? (kinetic) (b) 1,3-butadiene + HBr at 40 °C → ? (thermodynamic)

19.7 (routine) Why does 1,2-addition dominate at low T but 1,4-addition at high T?

19.8 (moderate) Sketch the allylic carbocation intermediate of HBr + 1,3-butadiene. Identify the two resonance structures. Which carbons are positively charged?

19.9 (challenge) Predict the products of: 1,3-cyclohexadiene + HBr. What's special about this substrate vs. 1,3-butadiene?

Section C — Diels-Alder fundamentals

19.10∗ (routine) Predict the product of: 1,3-butadiene + maleic anhydride → ?

19.11 (routine) Why is maleic anhydride an excellent dienophile? Identify two electron-withdrawing groups.

19.12∗ (routine) Sketch the cyclic 6-electron TS of a Diels-Alder. Identify which orbitals interact (diene HOMO + dienophile LUMO).

19.13 (routine) Why must the diene be in s-cis for Diels-Alder?

19.14 (moderate) Predict the product of: 1,3-butadiene + ethyl acrylate (CH₂=CHCO₂Et) → ?

19.15 (moderate) Predict the product of: cyclopentadiene + maleic anhydride → ? (norbornene-like product).

Section D — Stereochemistry

19.16∗ (routine) Predict the stereochemistry of: 1,3-butadiene + (E,E)-2,4-hexadienedicarboxylic acid → ? (the diene with cis-substituents on dienophile gives cis-product; with trans gives trans).

19.17 (routine) Why is the Diels-Alder stereospecific (cis dienophile → cis product)?

19.18 (moderate) Apply the endo rule: cyclopentadiene + maleic anhydride → predict the major product. Is the anhydride endo or exo?

19.19 (moderate) Why does the endo TS give kinetic preference? (Secondary orbital interactions.)

19.20 (challenge) Predict the major Diels-Alder product when both endo and exo are possible. Use the endo rule.

Section E — Frontier molecular orbital (FMO)

19.21∗ (routine) Diene HOMO + dienophile LUMO interaction is bonding. Sketch the orbitals (in-phase at both ends; productive overlap).

19.22 (routine) Why does an electron-withdrawing group on the dienophile increase Diels-Alder rate? Connect to LUMO energy.

19.23 (moderate) Why is cyclopentadiene more reactive than 1,3-butadiene in Diels-Alder? Multiple reasons.

19.24 (challenge) Inverse-electron-demand Diels-Alder: electron-poor diene + electron-rich dienophile. Sketch the FMO interaction.

Section F — [2+2] vs [4+2]

19.25∗ (routine) Why is [2+2] cycloaddition thermally forbidden? Use FMO arguments.

19.26 (routine) Why is [2+2] photochemically allowed?

19.27 (moderate) Calculate the total electron count for various cycloadditions: (a) [4+2] (Diels-Alder) (b) [2+2] (c) [3+2] (1,3-dipolar; dipole has 4 π electrons + dipolarophile has 2) (d) [6+4]

Which are thermally allowed (4n+2 = 6, 10, ...)?

19.28 (challenge) Predict the product of a 1,3-dipolar cycloaddition: nitrone + alkene → isoxazolidine.

Section G — Variants

19.29∗ (routine) Sketch an intramolecular Diels-Alder (IMDA) example. Why is IMDA often preferred over intermolecular?

19.30 (routine) Hetero-Diels-Alder: diene + C=N → ? Identify the heterocyclic product.

19.31 (moderate) Asymmetric Diels-Alder: diene + chiral oxazolidinone-substituted dienophile → ?. Sketch the principle.

19.32 (challenge) Retro-Diels-Alder: at high T, the cyclohexene reverts to diene + dienophile. When is this useful in synthesis?

Section H — Multistep synthesis

19.33∗ (routine) Design a synthesis using a Diels-Alder to build a complex 6-membered ring with 4 stereocenters.

19.34 (moderate) Use Diels-Alder + reduction to make a cis-fused bicyclic system.

19.35 (challenge) Design a synthesis of a steroid intermediate using Diels-Alder to set the C/D ring junction stereochemistry.

19.36 (challenge) Design a synthesis using IMDA: a linear precursor with diene and dienophile tethered together; cycloaddition gives a bicyclic product.

Section I — Industrial / natural product applications

19.37 (routine) Industrial Diels-Alder: 1,3-butadiene + maleic anhydride → cyclohex-4-ene-1,2-dicarboxylic anhydride. What's the use of this product?

19.38 (moderate) Cyclopentadiene + cyclopentadiene → dicyclopentadiene (a Diels-Alder dimer). Why does this dimer form spontaneously?

19.39 (challenge) Total synthesis of taxol uses Diels-Alder at multiple steps. Identify what kinds of bonds are formed.

Section J — Spectroscopy

19.40∗ (routine) Conjugated dienes show UV absorption at higher wavelength than isolated dienes. Why?

19.41 (moderate) Use UV-Vis spectroscopy to distinguish 1,3-butadiene (conjugated) from 1,4-pentadiene (isolated).

19.42 (challenge) A Diels-Alder product shows new ¹H NMR features at δ 5.5-6.0 (alkene) and the carbonyl signals from the dienophile. Identify the diagnostic peaks.

Section K — Open-ended

19.43 (challenge) Compare Diels-Alder with Robinson annulation (Ch 29). Both build 6-membered rings. Why might you use one over the other?

19.44 (challenge) Why is the Diels-Alder so widely used in natural product synthesis? Identify three reasons.

19.45 (challenge) Modern asymmetric Diels-Alder uses chiral catalysts (Lewis acid, organocatalyst, or chiral auxiliary). Sketch the principle.

Notes for instructors: Common stumbling blocks for Chapter 19: (1) Mismatching s-cis/s-trans with cis/trans of alkenes. (2) Forgetting that diene HOMO + dienophile LUMO is the relevant interaction. (3) Confusing endo/exo. (4) Not predicting all 4 stereocenters. Computational exercises: visualize MOs of 1,3-butadiene; identify HOMO and LUMO; predict orbital symmetry in cycloadditions.