Using Alkene Reactions In Synthesis

Using Alkene Reactions in Synthesis

Using Alkene Reactions in Synthesis

Alkenes are synthesis hubs: you can add across them to install new functional groups or form them by elimination when you need a handle for the next step.

The Alkene Reaction Map

  • Additions (π → σ): HX (alkyl halide), X₂ (vicinal dihalide), X₂/H₂O (halohydrin), H₂O/H⁺ or Hg(OAc)₂/H₂O/NaBH₄ (Markovnikov alcohol), BH₃·THF then H₂O₂/NaOH (anti-Markovnikov alcohol), ROH/Hg²⁺ (ether), OsO₄ or cold KMnO₄ (syn 1,2-diol), epoxidation then ring-opening (anti diol), H₂/Pd (alkane).
  • Cleavage: O₃ then workup (aldehydes/ketones; oxidative workup → acids where applicable), hot KMnO₄ (cleavage to carbonyls/acids).
  • Forming alkenes (σ → π): E2 of alkyl halides (strong base), acid-catalyzed dehydration of alcohols.

Planning Patterns

  • Regiochemistry: Use Markovnikov paths for substituted alcohols/halides; use anti-Markovnikov (peroxides or hydroboration) when the group must land on the less substituted carbon.
  • Stereochemistry: Pick syn vs anti additions to match the target (e.g., syn diol via OsO₄ vs anti via epoxide opening).
  • Protect/convert: Halohydrin → epoxide (base-induced ring closure); dihalide → elimination to alkyne (later chapters).
  • Retro hints: See an alcohol? Think hydration or hydroboration of an alkene. See a vicinal dihalide? Think X₂ addition. Need to break a chain into carbonyls? Consider ozonolysis.

Worked Examples (Text-Only Planning)

  • 2-Bromopropane: Propene + HBr (Markovnikov) → 2-bromopropane.
  • 1-Propanol: Propene + BH₃·THF then H₂O₂/NaOH (anti-Markovnikov) → 1-propanol.
  • trans-1,2-Dibromocyclohexane: Cyclohexene + Br₂ (anti addition) → trans-1,2-dibromide.
  • Epoxide from cyclohexene: Cyclohexene → (mCPBA) epoxide; or via halohydrin then base.

Multi-Step Strategy Template

  1. Choose/forge the alkene: Eliminate from an alcohol or alkyl halide if needed.
  2. Pick the addition: Match regio- and stereochemistry to the target.
  3. Post-process: Use substitutions/eliminations on the new group (e.g., halide → elimination, halohydrin → epoxide).
  4. Check compatibility: Avoid rearrangements (use oxymercuration or hydroboration); avoid over-reduction if other groups are present.

Summary

  • Alkenes enable predictable functional-group installs; select reagents for the right regio/stereo outcome.
  • Elimination gives you the alkene handle; addition converts it to what you need next.
  • Ozonolysis and dihydroxylation provide powerful disconnects for retrosynthesis.