Overview
Hydroboration-oxidation is a two-step sequential reaction that converts alkenes to alcohols with opposite regioselectivity compared to acid-catalyzed water addition. This method avoids carbocation formation and allows placement of the hydroxyl group on the less substituted carbon.
Comparison of Alkene-to-Alcohol Conversions
| Method | Electrophile | Nucleophile | Product Regioselectivity | Carbocation Formed? |
|---|
| Acid-Catalyzed Water Addition | H⁺ (hydrogen ion) | H₂O (water) | OH on more substituted carbon (e.g., 2-propanol) | Yes (rearrangements possible) |
| Hydroboration-Oxidation | BH₃ (borane) | H⁻ (hydride ion, then OH⁻) | OH on less substituted carbon (e.g., 1-propanol) | No (no rearrangements) |
Hydroboration (Step 1)
- Reagent: Borane (BH₃) in tetrahydrofuran (THF).
- THF role: Stabilizes borane; without it, diborane (B₂H₆) forms—a dangerous, explosive, flammable, toxic gas.
- Borane structure: SP² hybridized with three σ bonds to hydrogen and an empty p orbital.
- Empty p orbital accepts electron pairs, making borane an electrophile despite lacking positive charge.
- Mechanism: Concerted reaction where all bond-making and bond-breaking occur simultaneously.
- π electrons attack boron while a hydride ion (H⁻) transfers to the other SP² carbon.
- Produces alkylborane (R–BH₂), which can react further to form dialkylborane (R₂BH) and trialkylborane (R₃B).
Regioselectivity and Transition State Stability
- Electrophile adds to the SP² carbon with the most hydrogens (least substituted carbon).
- Reason: Transition state is carbocation-like with partial positive charge on other carbon.
- More substituted carbons stabilize partial positive charges better than less substituted carbons.
- Same rule applies to both acid-catalyzed addition (H⁺) and hydroboration (BH₃).
- Result: Hydroxyl group ultimately attaches to least substituted carbon after oxidation.
Using 9-BBN (9-Borabicyclo[3.3.1]nonane)
- Structure: Borane with two bulky alkyl groups and one hydride ion.
- Advantages: Only one hydride available, so only one alkyl group adds to alkene.
- Prevents formation of dialkyl and trialkyl substituted boranes (unwanted byproducts).
- Bulky R groups increase selectivity for less substituted SP² carbon.
- Preferred when single, specific product is desired.
Oxidation (Step 2)
- Reagents: Aqueous sodium hydroxide (NaOH) and hydrogen peroxide (H₂O₂).
- Replaces boron with hydroxyl (–OH) group to form alcohol.
- Mechanism steps:
- Hydroperoxide ion (OOH⁻) attacks boron (nucleophile attacks electrophile).
- 1,2-alkyl shift displaces hydroxide ion; relieves negative charge on boron.
- Hydroxide ion attacks boron again.
- Alkoxide ion (RO⁻) leaves.
- Alkoxide ion is protonated by water to form alcohol.
- All steps are reversible; reaction proceeds toward stable products.
Key Terms & Definitions
- Concerted Reaction: All bond-making and bond-breaking occur in a single step.
- Oxidation: Reaction increasing carbon–oxygen bonds or decreasing carbon–hydrogen bonds.
- Hydride Ion (H⁻): Hydrogen atom with two electrons; negatively charged nucleophile.
- Alkoxide Ion (RO⁻): Deprotonated alcohol; oxygen with negative charge bonded to alkyl group.
- 1,2-Alkyl Shift: Migration of alkyl group with its bonding electrons to adjacent atom.
Advantages of Hydroboration-Oxidation
- No carbocation intermediates form, so no carbocation rearrangements occur.
- Allows synthesis of alcohols with hydroxyl on less substituted carbon.
- Predictable product formation when carbocation rearrangements would complicate acid-catalyzed methods.
- Complements acid-catalyzed addition by providing opposite regioselectivity.
Action Items / Next Steps
- Practice two homework problems provided for this section.
- Review end-of-chapter problems for additional practice.
- Reach out with questions or clarification requests on complex mechanisms.