Oxymercuration-Reduction

The oxymercuration reaction stands as a pivotal electrophilic addition process that converts alkenes into neutral alcohols. This transformation involves the reaction of an alkene with mercuric acetate in a watery medium, leading to the concurrent addition of acetoxymercury and hydroxy groups across the alkene’s double bond. Notably, this reaction proceeds without the formation of carbocations, thereby eliminating the possibility of rearrangements. Adhering to Markovnikov’s rule, the hydroxy group is consistently added to the carbon with greater substitution, and the addition is of an anti nature, meaning the added groups are positioned trans to each other. The oxymercuration reaction is typically followed by reductive demercuration, collectively known as the oxymercuration–reduction or oxymercuration–demercuration reaction.

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The entire oxymercuration process unfolds in three distinct steps, often referred to as deoxymercuration. Initially, the alkene’s nucleophilic double bond engages with the mercury ion, displacing an acetoxy group and forming a positively charged mercurinium ion. Subsequently, a water molecule, acting as a nucleophile, attacks the more substituted carbon, which results in the neutralization of the mercury ion and imparts a positive charge to the oxygen atom. The final step involves the deprotonation of the alkyloxonium ion by an acetate ion, culminating in the formation of the alcohol product.

Oxymercuration is characterized by its high regioselectivity and serves as a classic example of a Markovnikov reaction. In all but the most exceptional cases, the water nucleophile preferentially targets the more substituted carbon. This selectivity is elucidated by analyzing the resonance structures of the mercuronium ion. Occasionally, the mercury’s positive charge is located on the more substituted carbon, creating a highly reactive temporary tertiary carbocation, which is then attacked by the nucleophile.

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From a stereochemical perspective, oxymercuration is an anti addition. Due to steric hindrance, the nucleophile cannot approach the carbon from the same side as the mercury ion6. Consequently, the hydroxy and acetoxymercury groups are invariably trans to each other when free rotation around the bond is restricted. 

 

In the oxymercuration process, the anti addition mechanism is favored due to the optimal orbital interaction between the water molecule’s lone pair and the vacant orbital of the mercuronium ion, which is situated on the opposite side of the acetoxymercury group. This orientation ensures regioselectivity, with the water molecule preferentially attacking the more substituted carbon atom. However, the water molecule does not add in a syn fashion across the double bond, suggesting that the transition state is structured to facilitate an attack from the side opposite the acetoxymercury group.

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Upon completion of the oxymercuration reaction, the resulting mercury-containing product is typically subjected to a demercuration process using sodium borohydride in an aqueous base. This step involves a reductive elimination reaction that replaces the acetoxymercury group with a hydrogen atom, without regard for stereochemistry. Consequently, the oxymercuration-reduction sequence culminates in the addition of water across the double bond, with the potential for either cis or trans configuration between the hydrogen and hydroxy groups. This method is widely employed in laboratories to hydrate alkenes following Markovnikov’s rule, while simultaneously preventing carbocation rearrangements that could otherwise lead to complex mixtures of products.