8.9 : Regioselectivity and Stereochemistry of Hydroboration

Hydroboration–oxidation reactions of alkenes exhibit specific regiochemical and stereochemical outcomes.

Recall that the hydroboration mechanism is a concerted process that proceeds via a cyclic four-atom transition state to form the anti-Markovnikov product.

The observed regioselectivity can be explained by a combination of steric and electronic factors.

In the steric framework, the addition of BH₂ at the less substituted carbon and the addition of hydrogen at the more substituted carbon minimizes the steric strain and forms a less-crowded, low-energy transition state; this is more stable than the Markovnikov transition state.

In the electronic context, as the alkene reacts with borane, either of the two carbons across the double bond can acquire a partial positive charge.

However, a positive charge on the more substituted carbon makes the transition state more stable. For this to take effect, BH₂ must add to the less substituted carbon, thereby justifying the observed anti-Markovnikov orientation.

The hydroboration step follows a syn-stereospecific addition where boron and hydrogen add to the alkene from the same face of the double bond. Three successive additions form a trialkylborane.

The oxidation step proceeds with the deprotonation of hydrogen peroxide to hydroperoxide, which attacks the trialkylborane to form an unstable intermediate. Next, an alkyl group migrates from boron to oxygen with the loss of a hydroxide ion.

In this case, the alkyl group migration occurs with the retention of configuration at the migrating carbon.

Repetition of these steps yields a trialkoxylborane, which is attacked by another hydroxide ion. Next, the departure of the alkoxide ion, followed by its protonation, forms an alcohol.

In the oxidation step, the hydroxyl group replaces boron while leaving the stereochemistry intact.

Lastly, since hydroboration–oxidation is stereospecific, it limits the number of stereoisomers that can be obtained. Thus, if the product is an alcohol with two stereocenters, out of the four possible stereoisomers, only those that conform with syn addition are formed.