Name: hydroboration reaction paths and product control
Uploaded: 2023-04-30T18:28:37.000Z
Duration: 2 min 36 s
Channel: JoVE

Hydroboration&#8211;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&#8211;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.

regioselectivity and stereochemistry of hydroboration

Regioselectivity and Stereochemistry of Hydroboration

A significant aspect of hydroboration&#8211;oxidation is the regio- and stereochemical outcome of the reaction.
Hydroboration proceeds in a concerted fashion with the attack of borane on the &#960; bond, giving a cyclic four-centered transition state. The &#8211;BH2 group is bonded to the less substituted carbon and &#8211;H to the more substituted carbon. The concerted nature requires the simultaneous addition of &#8211;H and &#8211;BH2 across the same face of the alkene giving syn stereochemistry.
<img alt="Hydroboration mechanism diagram, showing molecular steps and transition state equations in process." src="/files/ftp_upload/11780/11780_PT_Figure_1.svg" style="text-align: center; height: 225px;" data-altupdatedat="1761830439000" data-alt="Figure1" />
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 (&#8211;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.
<img alt="Organic chemistry diagram, borane molecule structure with methyl groups, illustrating bonding." src="/files/ftp_upload/11780/11780_PT_Figure_2.svg" style="text-align: center; height: 100px;" data-altupdatedat="1761830439000" data-alt="Figure2" />
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, &#8211;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.
<img alt="Organic reaction mechanism diagram showing chemical transformations and intermediates." src="/files/ftp_upload/11780/11780_PT_Figure_3.svg" style="text-align: center; height: 300px;" data-altupdatedat="1761830439000" data-alt="Figure3" />
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.
<img alt="Hydroboration-oxidation of alkenes; BH3, H2O2, NaOH; reaction mechanism diagram." src="/files/ftp_upload/11780/11780_PT_Figure_4.svg" style="text-align: center; height: 70px;" data-altupdatedat="1761830439000" data-alt="Figure4" />

A significant aspect of hydroboration&#8211;oxidation is the regio- and stereochemical outcome of the reaction.
Hydroboration proceeds in a concerted ...

regioselectivity-and-stereochemistry-of-hydroboration

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JoVE Core

Organic Chemistry

Unit 1

Reactions of Alkenes

KEY TERMS AND CONCEPTS

hydroboration reaction paths and product control

Hydroboration shows how alkene reactions control both where atoms add and how the product is shaped. In hydroboration–oxidation, borane attacks the alkene π bond in a concerted way, which means the bond changes happen together. This forms a cyclic, four-centered transition state.

In this transition state, the BH2 group attaches to the less substituted carbon, while H attaches to the more substituted carbon. The addition happens across the same face of the alkene, so the reaction gives syn stereochemistry. Syn addition means both new groups enter from the same side.

The regioselectivity of hydroboration can be explained by steric and electronic factors. The larger BH2 group on the less substituted carbon creates less steric tension, so the transition state is less crowded and lower in energy. Electronic effects also matter because a partial positive charge on the more substituted carbon is more favorable and gives a more stable transition state, which supports the anti-Markovnikov orientation.

The oxidation step changes the hydroboration product, and the alkyl group migrates with retention of configuration. Retention of configuration means the migrating group moves with its electron pairs without changing the tetrahedral shape of the carbon. Because the reaction is stereospecific, the number of chiral centers formed must be tracked. If one chiral center forms, both enantiomers can appear because syn addition can happen from either face of the alkene with equal probability. If two chiral centers form, the syn addition determines which pair of enantiomers is formed most often.

Hydroboration Reaction Paths and Product Control

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Hydrogen bromide can add to an alkene in a way that goes against Markovnikov’s rule when organic peroxides are present. For example, 2-methylpropene reacts with HBr and peroxide to give 1-bromo-2-methylpropane. This change in product comes from a free radical mechanism, which reverses the usual regioselectivity. The reaction has three stages: initiation, propagation, and termination. In initiation, an oxygen-oxygen bond in the radical initiator breaks by homolytic cleavage, meaning each atom...

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Carbocation Stability in Alkene Hydration

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Anti-Markovnikov Alcohols from Alkenes

Hydroboration-oxidation turns alkenes into alcohols with anti-Markovnikov orientation. It is a complementary route to oxymercuration-demercuration, which gives Markovnikov products. In this reaction, borane adds across the alkene first, and basic hydrogen peroxide finishes the conversion to an alcohol. Borane is very reactive because the boron atom has only six electrons in its valence shell. It also has an empty 2p orbital that sits perpendicular to the plane formed by boron and its three...

Hydroboration shows how alkene reactions control both where atoms add and how the product is shaped. In hydroboration–oxidation, borane attacks the alkene π bond in a concerted way, which means the bond changes happen together. This forms a cyclic, four-centered transition state. In this transition state, the BH2 group attaches to the less substituted carbon, while H attaches to the more substituted carbon. The addition happens across the same face of the alkene, so the reaction gives syn...

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Chiral Alkene Hydrogenation for Drug Synthesis

Catalytic hydrogenation adds molecular hydrogen to an alkene double bond and turns it into an alkane. A transition-metal catalyst drives the reaction, and the hydrogen atoms add in syn stereochemistry, meaning they enter from the same side. The catalyst can be heterogeneous or homogeneous. When hydrogenation creates a chiral center, the products are usually a pair of enantiomers, which are mirror-image molecules. An enantiomeric excess of one product can be obtained with an enantioselective...

key terms and concepts

Learn how hydroboration–oxidation controls regioselectivity, syn addition, anti-Markovnikov orientation, and retention of configuration in alkene reactions.

Hydroboration Reaction Paths and Product Control | JoVE K12

organic chemistry

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Hydroboration Reaction Paths and Product Control

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