Name: anti-markovnikov alcohols from alkenes
Uploaded: 2025-05-22T09:05:34.000Z
Duration: 3 min 8 s
Channel: JoVE

In addition to oxymercuration-reduction, hydroboration-oxidation is another significant reaction that converts an alkene into an alcohol. However, unlike oxymercuration-reduction, hydroboration-oxidation proceeds with anti-Markovnikov&#39;s regioselectivity.
This is a two-step transformation. The first step is hydroboration, in which borane dissolved in tetrahydrofuran adds to an alkene to form an organoborane intermediate, followed by the oxidation of the intermediate using hydrogen peroxide to yield an alcohol.
The boron atom in borane has a vacant 2p orbital and an incomplete octet, thereby making it electron-deficient and electrophilic.
Monomeric borane is unstable and readily dimerizes into diborane. However, it can be stabilized in a solvent, such as tetrahydrofuran, which donates an electron pair into the vacant 2p boron orbital, forming a stable boron-ether complex.
The hydroboration mechanism proceeds with the attack on borane by the alkene &#960; electrons in a concerted manner. This leads to a transition state where boron is partially bonded to the less substituted and less sterically hindered carbon.
The net result is a syn-addition of BH2 and hydrogen across the alkene double bond, forming an alkylborane.
Successive addition of two alkene molecules produces a trialkylborane.
The second part of the reaction is oxidation. Here, a hydroxide ion deprotonates the hydrogen peroxide to form a hydroperoxide, which further acts as a nucleophile and attacks the trialkylborane to yield an unstable intermediate.
Next, the migration of an alkyl group from boron to the adjacent oxygen atom results in the expulsion of a hydroxide ion to form an alkoxyborane. These steps are repeated to convert the trialkylborane into a trialkoxyborane.
The boron atom of the trialkoxyborane further undergoes a nucleophilic attack by another hydroxide ion. Lastly, the departure of the alkoxide ion followed by its protonation produces the target alcohol.
Thus, the hydroboration-oxidation of 2-methyl-2-butene, being syn stereoselective, forms a pair of enantiomeric 3-methyl-2-butanol molecules with anti-Markovnikov&#39;s regioselectivity. In contrast, the lack of stereoselectivity in oxymercuration-reduction yields 2-methyl-2-butanol in syn and anti configuration as per Markovnikov&#39;s regioselectivity.

hydroboration-oxidation of alkenes

Hydroboration-Oxidation of Alkenes

In addition to the oxymercuration&#8211;demercuration method, which converts the alkenes to alcohols with Markovnikov orientation, a complementary hydroboration-oxidation method yields the anti-Markovnikov product. The hydroboration reaction, discovered in 1959 by H.C. Brown, involves the addition of a B&#8211;H bond of borane to an alkene giving an organoborane intermediate. The oxidation of this intermediate with basic hydrogen peroxide forms an alcohol.
<img alt="Organic chemistry reaction diagram showing alkene hydroxylation: oxymercuration and hydroboration." src="/files/ftp_upload/11779/11779_PT_Figure_1.svg" style="text-align: center; height: 140px;" data-altupdatedat="1754904545000" data-alt="Alkene hydration reactions diagram; shows oxymercuration-demercuration and hydroboration-oxidation." />
Borane as a reagent is very reactive, as the boron atom has only six electrons in its valence shell. The unoccupied 2p orbital of the boron is perpendicular to the plane, which is occupied by the boron and the three other hydrogens oriented at an angle of 120&#176;. Thus, borane is electrophilic with its structure resembling a carbocation without any charge.
<img alt="Borane molecular diagram; electron-deficient, electrophilic, 6e- notation; chemistry concept." src="/files/ftp_upload/11779/11779_PT_Figure_2.svg" style="text-align: center; height: 210px;" data-altupdatedat="1754904545000" data-alt="Borane structure diagram showing electron-deficiency, electrophilic properties, and 6 electrons configuration." />
Due to high reactivity, two borane molecules dimerize such that two hydrogen atoms are partially bonded to two boron atoms with a total of two electrons. Hence, they are called three-center, two-electron bonds. Diborane co-exists in equilibrium with a small amount of borane. 
<img alt="Chemical reaction diagram, B2H6 formation from B2H4, illustrating borane bonding process." src="/files/ftp_upload/11779/11779_PT_Figure_3.svg" style="text-align: center; height: 50px;" data-altupdatedat="1754904545000" data-alt="Chemical bonding process diagram, B2H6 formation equation, depicts electron sharing mechanism" />
The electron-deficient borane easily accepts an electron pair from tetrahydrofuran to complete its octet forming a stable borane-ether complex. This is used as a reagent in hydroboration reactions under an inert atmosphere to avoid spontaneous ignition in the air.
<img alt="Lewis acid-base reaction; chemical equation illustrating borane-tetrahydrofuran coordination." src="/files/ftp_upload/11779/11779_PT_Figure_4.svg" style="text-align: center; height: 80px;" data-altupdatedat="1754904545000" data-alt="Lewis structure diagram of borane reacting with tetrahydrofuran showing electron pair donation." />
<h4>Hydroboration Mechanism</h4>
The mechanism starts with a borane attacking the &#960; bond at the less substituted and sterically less hindered site of an alkene forming a cyclic transition state. The overall result is a syn-addition of BH2 and hydrogen across the alkene double bond, producing an alkylborane. The reaction of a second alkene with the alkylborane yields a dialkylborane followed by the addition of a third alkene to produce a trialkylborane.
<img alt="Hydroboration mechanism: Borane addition to alkene, transition state, boron intermediate diagram." src="/files/ftp_upload/11779/11779_PT_Figure_5.svg" style="text-align: center; height: 200px;" data-altupdatedat="1754904545000" data-alt="Hydroboration mechanism diagram; boron addition to alkene, transition state, product formation." />
<h4>Oxidation Mechanism</h4>
The oxidation begins with the deprotonation of hydrogen peroxide by a hydroxide ion forming a hydroperoxide. The hydroperoxide acts as a nucleophile and attacks the trialkylborane, resulting in an unstable intermediate. This is followed by the migration of an alkyl group from boron to the adjacent oxygen atom, releasing a hydroxide ion. This series of three steps is repeated to convert the remaining trialkylborane into a trialkoxyborane.
The boron atom of the trialkoxyborane is attacked by the nucleophilic hydroxide ion with the subsequent departure of the alkoxide ion neutralizing the formal charge on the boron atom. Finally, protonation of the alkoxide ion gives an alcohol as the final product.
<img alt="Chemical reaction mechanism with bond interactions, involves boron; reaction diagram." src="/files/ftp_upload/11779/11779_PT_Figure_6.svg" style="text-align: center; height: 320px;" data-altupdatedat="1754904545000" data-alt="Boron-catalyzed hydroperoxide reaction mechanism; chemical equations; process diagram." />

In addition to the oxymercuration&#8211;demercuration method, which converts the alkenes to alcohols with Markovnikov orientation, a complementary ...

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Organic Chemistry

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Reactions of Alkenes

KEY TERMS AND CONCEPTS

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 hydrogens, which are arranged at about 120 degrees. This makes borane electrophilic, and its shape can resemble a carbocation without a charge. Because of this high reactivity, two borane molecules dimerize. In that form, two hydrogen atoms are shared between two boron atoms in three-center, two-electron bonds. Diborane stays in equilibrium with a small amount of borane, and borane can also accept an electron pair from tetrahydrofuran to form a stable borane-ether complex. That complex is used in hydroboration under an inert atmosphere to help prevent spontaneous ignition in air.

The hydroboration step begins when borane attacks the pi bond of an alkene at the less substituted and less crowded carbon. The reaction goes through a cyclic transition state. The result is syn-addition, so BH2 and hydrogen add to the same side of the double bond. This forms an alkylborane. A second alkene can react with that product to make a dialkylborane, and a third alkene can then form a trialkylborane.

Oxidation begins when hydroxide ion removes a proton from hydrogen peroxide to form a hydroperoxide. The hydroperoxide then acts as a nucleophile and attacks the trialkylborane, giving an unstable intermediate. Next, an alkyl group moves from boron to the nearby oxygen atom, and hydroxide ion is released. This sequence repeats until a trialkoxyborane forms. Finally, hydroxide attacks the boron, the alkoxide leaves, and protonation of the alkoxide gives the alcohol product.

Anti-Markovnikov Alcohols from Alkenes

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key terms and concepts

Learn how hydroboration-oxidation converts alkenes to alcohols with anti-Markovnikov orientation through syn-addition and oxidation with hydrogen peroxide.

Anti-Markovnikov Alcohols from Alkenes | JoVE K12

organic chemistry

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Anti-Markovnikov Alcohols from Alkenes

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