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.
8.9:
Regioselectivity and Stereochemistry of Hydroboration
A significant aspect of hydroboration–oxidation is the regio- and stereochemical outcome of the reaction.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
The observed preference in regioselectivity can be explained on the basis of steric and electronic factors.
In the transition state, the larger part of the reagent (–BH2) is bonded to the less substituted carbon, thereby minimizing the steric tension. This results in a less crowded low-energy transition state, which is more stable than Markovnikov's transition state.
Further, the addition of borane can result in a partial positive charge on either of the two carbons. However, a partial positive charge on the more substituted carbon is highly favorable, as it gives a more stable transition state. Hence, in order to achieve this, –BH2 must be placed at the less substituted carbon resulting in an anti-Markovnikov orientation.
The second part of the reaction is the oxidation of the product obtained from hydroboration.
The migration of the alkyl group in this mechanism occurs with retention of configuration as it transfers with the electron pairs without reconstructing the tetrahedral geometry of the migrating carbon.
Since the reaction is stereospecific, it is essential to recognize the number of chiral centers formed. If one chiral center is formed, both enantiomers are obtained, as syn addition can occur from either face of the alkene with equal probability. However, if two chiral centers are formed, the syn addition dictates which pair of enantiomers is predominantly obtained.
