This article explores hydroboration oxidation, a useful reaction in synthetic organic chemistry to add a single alcohol to an alkene.
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Reactants for Hydroboration Oxidation
Diborane is a boron hydride that dimerizes at STP to form a molecule with the formula B2H6. This unconventional bonding combined with boron’s unusual metalloid behavior creates a potent electrophile, which is especially important for hydroboration.
Hydrogen peroxide is a strong oxidizer in aqueous solution, and eventually produces the hydroperoxide anion in this reaction, which is the active oxidizing species. Additionally, hydrogen peroxide is a good source of hydroxide anions, which are also useful to this reaction.
Not always used in hydroboration oxidation, the addition of an Arrhenius base improves the yield for regiospecific hydroboration oxidation by exploiting Le Chatelier’s principle. Arrhenius bases contain a positive alkali cation (i.e. Na+, K+, Mg2+, etc.) and the negative hydroxide anion (OH–).
Tetrahydrofuran (THF) is the most common solvent for this reaction. THF is a Lewis base, and thus is used to stabilize the diborane in solution and prevents it from splitting into the borane monomers. Also used for this purpose is diglyme, also a Lewis acid. THF does not react during the main mechanism, and is effective at solvating both hydrocarbons and hydrocarbon-alcohols.
Mechanism of Hydroboration Oxidation
1. Diborane disassociates into two BH3, later, the pi electron pair from the alkene attacks the boron atom.
2. An intermediate forms where the boron bonds to the more accessible carbon. Electrons flow from the B-H bond to a H atom in borane, conferring a negative charge which then donates the pair to the carbocation. Note that the carbocation cannot migrate due to the filled octet of the adjacent carbon. This differs from traditional electrophilic substitution, and hence explains why the major product does NOT obey Markovnikov’s rule.
3. The alkene is successfully underwent hydroboration so that a boron and hydrogen atoms added to different carbons with syn stereochemistry.
4. This reaction repeats similarly two more times with the remaining two hydrogen atoms on the borane, to yield the tri-substituted product.
5. Hydrogen peroxide intermittently disassociates into the hydroperoxide anion, which then attacks the substituted boron center.
6. An electron pair from the boron-carbon bond travels to the proximal oxygen atom, and the peroxide electron pair travels to the further oxygen, and eventually to one of the hydrocarbon groups, creating an ether-like intermediate:
7. (Not Shown) A hydroxide anion is also a product, making a basic solution. This is an important consideration if other parts of your reactant are base-sensitive.
8/9. This oxidation step continues two more times, inserting oxygen atoms between the boron and they hydroborated reactant.
10. Water hydrolyzes this structure at all three oxygen atoms to create boric acid, and the alcohol.
Stereochemistry of Hydroboration Oxidation Reactions
Hydroboration creates the anti-Markovnikov product. This means that the alcohol will end up on the less substituted carbon, while the hydrogen adds to the more substituted carbon.
Hydroboration/oxidation proceeds with syn stereochemistry, where the alcohol and hydrogen add to the same face of the double bond.
With no outstanding steric or electrical factors, the product will be racemic if the most substituted carbon on the alkene in the reactant is secondary.
Other Hydroboration Oxidation Reactions
Hydroboration oxidation can also proceed with other borane derivatives. By replacing some of the hydrogens on borane with engineered carbon groups, hydroboration of certain alkenes (regioselectivity) and in a certain direction (stereoselectivity) is certainly possible. This property makes synthesis of alcohols a very exact process, which is indeed very useful in the synthesis of medicinal molecules.
Additionally, alkynes undergo hydroboration to form an alcohol and an alkene, which undergoes keto-enol tautomerization to form a ketone.