The Regiochemistry of Hydroboration-Oxidation
In the previous post, we mentioned that Hydroboration-oxidation places the OH group on the less substituted carbon of an alkene. Overall, it is an anti-Markovnikov hydration of the alkene, which is the regioselectivity of this reaction.
A quick reminder of why we call it an anti-Markovnikov addition is that, in hydroboration–oxidation, the OH group ends up on the less substituted carbon of the alkene, which is opposite to Markovnikov hydration. In Markovnikov hydration, the OH group is installed on the more substituted carbon because the reaction proceeds through a carbocation intermediate that is stabilized at the more substituted position.
So, let’s see why the regiochemistry of the hydroboration oxidation follows the anti-Markovnikov path.
The Steric Effect on the Hydroboration-Oxidation of Alkenes
There are two reasons for this: steric and electronic. Both arise from the preferred orientation of BH₃ as it approaches the alkene in the concerted hydroboration step.
Sterically, boron is larger than hydrogen, so it prefers to bond to the less substituted carbon, where there is less crowding. At the same time, the hydrogen is transferred to the more substituted carbon.
Once again, notice that the first alignment minimizes the steric strain between the boron and the carbon since it is next to a secondary carbon, while the second possibility puts it next to a tertiary carbon.
To increase the steric factor and improve the regioselectivity of the hydroboration, dialkyl boranes are used instead of BH3. The most common one is 9-Borabicyclo[3.3.1]nonane or 9-BBN:
As an example, it increases the regioselectivity of the Hydration-oxidation of Ethylene Derivatives to almost 100 : 0.
The use of bulky alkylboranes for hydroboration-oxidation reactions is especially important when the substrate is an alkyne because their linear geometry makes the regioselectivity more challenging.
Both ends of the alkyne are more exposed and accessible to the reagent, and bulky alkylboranes are much more selective to add the boron atom to the less substituted carbon than BH3.
Notice that the product of the hydroboration-oxidation of terminal alkynes is an aldehyde, and we will discuss this in detail in the next post.
The Electronic Effect on the Hydroboration-Oxidation of Alkenes
Let’s also discuss the electronic effect on the regioselectivity of the hydroboration step of the alkene.
Because the alkene is the nucleophile and donates electron density to the electron-deficient boron as the new C-B bond forms, the transition state is polarized, with a partial negative charge developing on boron and a partial positive charge on the carbon. This partial positive charge is better stabilized by the more substituted carbon due to the electron-donating nature of the adjacent alkyl groups, making this transition state lower in energy.
These alkylboranes are later oxidized to boronic esters, which are eventually hydrolyzed to the corresponding alcohols. As a result, the OH group preferentially ends up on the less substituted carbon, while hydrogen is delivered to the more substituted carbon.
The Stereochemistry of Hydroboration-Oxidation
The overall conversion in hydroboration-oxidation of alkenes is the addition of H and OH groups across the double bond, forming anti-Markovnikov alcohols when an asymmetric alkene is used. The stereochemistry of this transformation is that the H and OH groups end up on the same side of the product. To understand why this is the case, first remember that hydroboration is a concerted process, and the BH₂ and H species add to the double bond simultaneously. As a result, they both add to the same face of the alkene, giving a syn addition.
Remember also that the double bond is planar, and that hydroboration can occur from either face of the alkene.
Regardless of the face of the double bond, the H and BH₂ groups are added to the same side of the double bond (syn addition). So, regiochemically, there is no difference where the addition occurs, but the two products formed are enantiomers because they are nonsuperimposable mirror images.
During the oxidation of the alkylboranes in the subsequent step, the C–B bond is replaced by a C–OH bond with retention of configuration at the carbon bearing boron, so the overall stereochemical relationship established in the hydroboration step is preserved in the final alcohol product.
Let’s show the overall conversion of asymmetric alkenes, where hydroboration-oxidation leads to a pair of enantiomeric alcohols in which the H and OH groups are on the same side of the molecule.
Although this is going to be the main outcome of the reaction you will see in your class, do not automatically assume that the alcohols are enantiomers because this depends on the structure of the alkene.
If the alkene is symmetrical, then the resulting alcohol is going to be achiral. On the other hand, if the starting alkene already contains a chiral center, then a pair of diastereomeric alcohols will be formed.
Summarizing the Regio and Stereochemistry of the Hydroboration-OXidation of Alkenes
Overall, hydroboration-oxidation is both regioselective and stereospecific. The OH group is delivered to the less substituted carbon of the alkene (anti-Markovnikov selectivity), while hydrogen is added to the more substituted carbon, a result controlled by steric and electronic effects in the concerted transition state.
The reaction proceeds through syn addition, meaning both H and BH₂ add to the same face of the double bond. Since the alkene is planar, addition can occur from either face, leading to a pair of enantiomeric alcohols. If there were a chiral center in the substrate, then the product would be a pair of diastereomers.
If no stereogenic center is present in the product, meaning the alkene was symmetric, then the two pathways give identical achiral products rather than enantiomers.
