Hydroboration-oxidation is a big deal in organic chemistry. It’s a way to add water to alkenes and alkynes in a specific way (called anti-Markovnikov addition). Herbert Charles Brown discovered this reaction, and it even won him the Nobel Prize in 1979.
Let’s break down the mechanism of hydroboration-oxidation, looking at how it works with both alkenes and alkynes. We’ll pay special attention to regioselectivity (where things attach) and stereochemistry (the 3D arrangement of atoms).
This reaction happens in two main steps: first, hydroboration, then oxidation.
Hydroboration-Oxidation of Alkenes: The Hydroboration Step
The first step in hydroboration-oxidation is hydroboration, in which borane (BH3) reacts with an alkene.
Borane as a Lewis Acid
Borane acts as a Lewis acid by accepting electrons from the alkene pi bond. It’s often used as a complex with tetrahydrofuran (THF).
Borane adds to the alkene in a concerted, one-step fashion, which means there’s no carbocation intermediate formed. That’s good news because it prevents molecular rearrangements.
Regioselectivity
The hydroboration step demonstrates anti-Markovnikov regioselectivity. In other words, the boron atom adds to the less substituted carbon atom. Steric hindrance, or the physical bulk of the substituents, is what dictates where the boron goes. Electronic factors play a role as well, but steric factors are usually more influential.
Stereochemistry
The addition of boron and hydrogen happens in a syn fashion: both add to the same face of the alkene. This is a stereospecific process. The reaction happens via a four-center transition state.
Oxidation: The Second Step of Hydroboration-Oxidation
The oxidation stage of hydroboration-oxidation converts the trialkylborane intermediate into an alcohol. This reaction typically uses hydrogen peroxide (H2O2) in a basic solution.
Here’s how it works:
- The base removes a proton from hydrogen peroxide, creating a hydroperoxide ion.
- This hydroperoxide ion, acting as a nucleophile, attacks the boron atom of the trialkylborane. The oxygen atom of the hydroperoxide bonds to the boron.
- Next, one of the alkyl groups attached to the boron migrates to the oxygen atom.
- Finally, the borate ester undergoes hydrolysis, which cleaves it apart. This yields an alcohol molecule and sodium borate.
Importantly, all three alkyl groups initially attached to the boron atom are converted into alcohol molecules during this process.
Hydroboration-Oxidation of Alkynes
Alkynes can also be converted to useful organic molecules via hydroboration-oxidation. The reaction proceeds in a manner similar to that of alkenes.
Hydroboration of Alkynes
Borane will add across the triple bond of an alkyne in much the same way it adds across the double bond of an alkene. The regioselectivity is also anti-Markovnikov, meaning that the boron atom bonds to the carbon with fewer substituents.
Using Bulky Borane Reagents to Control the Reaction
It can be tricky to halt the hydroboration of alkynes at the alkenylborane stage. To avoid over-hydroboration, chemists often use bulky borane reagents like disiamylborane (Sia2BH) or 9-borabicyclo[3.3.1]nonane (9-BBN).
Oxidation of Alkenylboranes
Oxidation with hydrogen peroxide converts alkenylboranes to enols, which then tautomerize to form aldehydes or ketones. The final product will depend on the substitution pattern of the starting alkyne.
Example
A terminal alkyne that undergoes hydroboration-oxidation will yield an aldehyde as the final product.
Putting It All Together
Hydroboration-oxidation is a highly versatile reaction that allows chemists to synthesize alcohols and aldehydes with anti-Markovnikov regioselectivity. In the case of alkenes, the reaction also offers excellent stereocontrol via syn addition.
The mechanism involves a hydroboration step followed by an oxidation step.
To get the best yields, it’s important to carefully select the reagents and control the reaction conditions. For example, bulky boranes are often used with alkynes.