Chapter 16 — Key Takeaways

What you should leave Chapter 16 with

  1. Alkene addition reactions install various functional groups across a C=C with predictable regio- and stereochemistry. The "toolbox" enables transformation of an alkene into many different products.

  2. Acid-catalyzed hydration (H₂O/H₂SO₄): Markovnikov alcohol. Mechanism: cation; rearrangements possible.

  3. Oxymercuration-demercuration (Hg(OAc)₂/H₂O, NaBH₄): Markovnikov alcohol with no rearrangement. The mercurinium ion intermediate prevents 1,2-shifts.

  4. Hydroboration-oxidation (BH₃, then H₂O₂/NaOH): anti-Markovnikov alcohol with syn stereochemistry. Boron adds to less-substituted C; oxidation converts B-C to OH-C with retention.

  5. Halogenation (Br₂/CCl₄): vicinal dibromide with anti stereochemistry (bromonium ion, backside attack).

  6. Halohydrin formation (Br₂/H₂O): bromohydrin with -OH at more-substituted C, -Br at less-substituted C, anti stereochemistry.

  7. Epoxidation (mCPBA): epoxide with syn stereochemistry (peroxyacid butterfly TS). Stereospecific: cis-alkene → cis-epoxide; trans → trans.

  8. Asymmetric epoxidation: - Sharpless AE: allylic alcohol + Ti(OiPr)₄ + chiral DET + TBHP → chiral epoxide. - Jacobsen: Mn-salen catalyst for non-functionalized alkenes.

  9. Dihydroxylation (OsO₄/NMO): syn 1,2-diol (cis). Catalytic Os with NMO recycling.

  10. Asymmetric dihydroxylation (Sharpless AD): chiral cinchona ligand on OsO₄ gives chiral cis-diol with high ee.

  11. Anti-1,2-diol (mCPBA + acid hydrolysis): epoxide formed, then opened with acid + water to give trans-diol.

  12. Ozonolysis (O₃, then workup): C=C cleavage. Reductive workup (Zn/HOAc, Me₂S) gives carbonyls. Oxidative workup (H₂O₂) gives COOHs.

  13. Catalytic hydrogenation (H₂/Pd, Pt, Ni): alkane with syn addition. Used for complete reduction.

  14. Lindlar Pd: selectively reduces alkynes to cis-alkenes (Ch 17). Doesn't reduce alkenes further to alkanes.

  15. Asymmetric hydrogenation (Knowles, Noyori 2001 Nobel): Rh-(R,R)-DiPAMP for α,β-unsaturated acids; Ru-BINAP for ketones. Gives chiral products from prochiral substrates.

  16. The reagent toolbox table: | Product | Reagent | Regio | Stereo | Rearrangement? | |---|---|---|---|---| | Markov alcohol | H₂O/H₂SO₄ | Markov | mixed | possible | | Markov alcohol (clean) | Hg(OAc)₂ + NaBH₄ | Markov | anti | none | | Anti-Markov alcohol | BH₃, H₂O₂ | anti-Markov | syn | none | | Vic-dibromide | Br₂ | n/a | anti | none | | Halohydrin | Br₂/H₂O | Markov-like | anti | none | | Epoxide | mCPBA | n/a | syn | none | | Syn-diol | OsO₄/NMO | n/a | syn | none | | Anti-diol | mCPBA + H₂O/H⁺ | n/a | anti | none | | Carbonyls | O₃ + Zn | n/a | n/a | none | | COOHs | O₃ + H₂O₂ | n/a | n/a | none | | Alkane | H₂/Pd | n/a | syn | none |

  17. Carbocation rearrangements are a concern only for cation-mediated reactions (acid-catalyzed hydration). Concerted reactions (BH₃, mCPBA, OsO₄, hydrogenation) don't have this issue.

  18. Industrial alkene chemistry:

    • Hydrogenation of vegetable oils → margarines (with trans-fat history).
    • Epoxidation of ethylene → ethylene oxide (precursor to glycol).
    • Hydroboration in pharma syntheses.
    • Sharpless AD in chiral pharma.

  19. Total synthesis applications: many alkene additions are used in natural product synthesis (e.g., Taxol used hydroboration, Sharpless AD, mCPBA, hydrogenation).

  20. Connection to other chapters:

    • Ch 15 introduced electrophilic addition basics.
    • Ch 17 will extend to alkynes.
    • Ch 18 covers radical addition (anti-Markovnikov HBr).
    • Ch 19 covers Diels-Alder (alkene as dienophile).
    • Ch 36-37 cover modern asymmetric versions.

Cross-references

  • Chapter 15 — Alkene structure and electrophilic addition (foundation).
  • Chapter 17 — Alkynes (similar chemistry on triple bonds).
  • Chapter 18 — Radical addition (anti-Markovnikov HBr).
  • Chapter 19 — Diels-Alder cycloaddition.
  • Chapter 25 — Nucleophilic addition to carbonyls (different reactivity).
  • Chapter 36 — Modern oxidation (Sharpless, Jacobsen).
  • Chapter 37 — Asymmetric hydrogenation.
  • Chapter 38 — Total synthesis applications (Taxol).
  • Appendix C — Reaction summary.
  • Appendix F — Named reactions.

Study tip

For each alkene reaction, ask: 1. What's the regiochemistry? Markovnikov, anti-Markovnikov, or n/a. 2. What's the stereochemistry? Syn, anti, or mixed. 3. What's the mechanism? Cation (rearrangement risk), concerted (no rearrangement), or radical. 4. What's the byproduct? Important for atom economy.

If you can answer these for any of the 11 reactions in the toolbox, you've internalized Chapter 16. Then synthesis design (Ch 31) becomes a matter of choosing the right tool for the job.