8.8:
Hydroboration-Oxidation of Alkenes
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'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 π 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's regioselectivity. In contrast, the lack of stereoselectivity in oxymercuration-reduction yields 2-methyl-2-butanol in syn and anti configuration as per Markovnikov's regioselectivity.
8.8:
Hydroboration-Oxidation of Alkenes
In addition to the oxymercuration–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–H bond of borane to an alkene giving an organoborane intermediate. The oxidation of this intermediate with basic hydrogen peroxide forms an alcohol.
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°. Thus, borane is electrophilic with its structure resembling a carbocation without any charge.
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.
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.
Hydroboration Mechanism
The mechanism starts with a borane attacking the π 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.
Oxidation Mechanism
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.
