22 1 Oxymercuration Demercuration Markovnikov addition

Oxymercuration-Demercuration Synthesis

• Purpose: Avoid rearrangements during the hydration of alkenes while still achieving a Markovnikov addition.

• Overall Reaction: Generates an alcohol using mercuric acetate, THF, and water without forming a discrete carbocation, thus preventing rearrangement.

Typical Reaction Conditions

• Reagents:

  • Mercuric acetate

  • THF (tetrahydrofuran)

  • Water

• After the reaction:

  • An -OH group is added to a carbon

  • An acetate is added to another carbon

• Reduction: Followed by reducing conditions to replace the mercury-carbon bond with a hydrogen.

Markovnikov Addition with Unsymmetrical Alkenes

• Example with Butene:

  • In oxymercuration step:

    • An -OH and mercury are added across the double bond.

  • Demerucation Step: Removes mercury and replaces it with hydrogen.

  • Resulting product is the more substituted alcohol, adhering to Markovnikov's rule.

Advantages of Oxymercuration-Demercuration

• No rearrangements unlike acid-catalyzed hydration, which often forms carbocations that can rearrange.

• Yields the Markovnikov product without altering the carbon skeleton.

Mechanism of Oxymercuration-Demercuration

1. Oxymercuration Step:

   • Polar mercury-oxygen bond creates electrophilic and nucleophilic sites.

   • Electrons from the double bond attack the electrophile, expelling acetate and forming a bridge with mercury.

   • The electrophile adds to the less substituted carbon, leading to a partial positive charge.

   • Water, acting as a nucleophile, attacks the positively charged carbon without undergoing rearrangement.

   • Final product of oxymercuration step involves an -OH addition formed with anti-configuration.

2. Stereochemistry:

   • The reaction proceeds with the -OH group attacking from the opposite side of the bridging mercury atom, attaining anti-addition.

   • In reduction, the stereochemical control is lost, resulting in both syn and anti addition of -OH and hydrogen.

Salvo Mercuration-Demercuration

• Modification: Replacing water with alcohol in the reaction.

• Product: Results in the formation of an ether, while still achieving Markovnikov addition.

• Final Outcome: Generates an ether instead of an alcohol through similar mechanisms.

Oxymercuration-Demercuration Synthesis

Purpose: This reaction method is designed to effectively add water across the double bonds of alkenes, while specifically avoiding carbocation rearrangements. By ensuring a Markovnikov addition, it produces the more stable and favored alcohol product without yielding rearranged byproducts.

Overall Reaction: The synthesis generates an alcohol through the interaction of mercuric acetate, tetrahydrofuran (THF), and water. This method is particularly advantageous as it circumvents the formation of discrete carbocations, which are often responsible for rearrangements in traditional hydration methods.

Typical Reaction ConditionsReagents:

• Mercuric acetate: Serves as the source of the mercuric cation, crucial for the first step of the reaction.

• THF (tetrahydrofuran): An aprotic solvent that stabilizes the reaction intermediates and enhances the reactivity of alkenes.

• Water: Acts as the nucleophile that will ultimately yield the alcohol product.

After the reaction, the following transformations occur:

• An -OH group is added to one carbon of the original double bond, resulting in the formation of an alcohol.

• An acetate group is introduced to another carbon of the original double bond, influencing the final structure of the product.

Reduction: Following the oxymercuration step, the reaction mixture undergoes reduction conditions to replace the mercury-carbon bond with a hydrogen atom, completing the alcohol formation process. Common reducing agents such as sodium borohydride (NaBH4) or zinc with acid may be used for this purpose.

Markovnikov Addition with Unsymmetrical AlkenesExample with Butene:

• In the oxymercuration step, an -OH group and a mercury group are added across the double bond of butene.

• Upon reaching the demercuration step, mercury is effectively eliminated from the structure, replaced by hydrogen, allowing the formation of the more substituted alcohol (2-butanol), consistent with Markovnikov's rule.

Advantages of Oxymercuration-Demercuration:

• The reaction cleanly avoids rearrangements that occur in acid-catalyzed hydration reactions due to carbocation intermediates.

• It guarantees a high yield of the Markovnikov product without modifying the overall carbon skeleton of the original alkene, which is crucial for synthetic organic chemistry applications.

Mechanism of Oxymercuration-Demercuration

1. Oxymercuration Step:

   • The formation of a polar mercury-oxygen bond creates distinct electrophilic and nucleophilic sites.

   • The alkenic double bond electrons attack the electrophilic mercury center, causing the expulsion of acetate and the formation of a cyclic mercurinium ion (a three-membered ring structure with mercury).

   • The electrophile preferentially adds to the less substituted carbon atom, leading to a partial positive charge on the more substituted carbon.

   • Water, acting as a nucleophile, will then attack the positively charged carbon, completing the addition without rearrangement.

   • The final product of this step features the -OH addition in an anti-configuration due to the sterics of the mercurinium ion.

2. Stereochemistry:

   • The attack of the -OH group occurs from the opposite side (anti-addition) of the bridging mercury atom, establishing stereochemical control during the reaction.

   • However, in the reduction step, this stereochemical control is lost, leading to a mixture of both syn and anti addition products of -OH and hydrogen.

Salvo Mercuration-Demercuration

• Modification: In certain variations of the oxymercuration-demercuration process, water is replaced with an alcohol as the nucleophile.

• Product: This alteration leads to the formation of an ether compound instead of an alcohol, while still adhering to Markovnikov addition.

• Final Outcome: Ultimately, this yields an ether product through mechanisms that parallel those seen in the traditional oxymercuration-demercuration sequence, expanding the utility of this reaction type in synthetic organic chemistry.