22 2 Hydroboration Oxidation Anti Markovnikov addition
Hydroboration-Oxidation Reaction
The hydroboration-oxidation reaction is a method for synthesizing alcohols from alkenes that provides strict control over the regioselectivity of the product, resulting in anti-Markovnikov addition.
Key Properties
Complementary to Oxymercuration-Demercuration: Produces anti-Markovnikov addition to double bonds.
Goal: Generate less substituted alcohols.
Mechanism Overview
Starting Materials: Alkene and hydroboration catalyst (borane).
Borane exists primarily as a dimer and is typically dissolved in solvents like THF or DMSO.
Initial Reaction: Addition of BH3 to double bond.
Example: Methylcyclopentene undergoes hydration to yield a regio-specific product with the OH group on the less substituted carbon.
Orientation: The H and OH groups are positioned in a syn configuration relative to each other.
Detailed Mechanism Steps
Step 1: Overlap of pi bond from alkene with the empty p orbital of boron.
Alkene donates electron density, leading to a partial positive charge developing on the more substituted carbon.
Step 2: Boron shifts, interacting with hydrogen orbital to form a transition state.
This designates the position of the boron on the less substituted carbon causing anti-Markovnikov selectivity.
Example Reaction
99:1 ratio favoring anti-Markovnikov addition.
Transition state facilitates the product with boron on the less substituted carbon and hydrogen on the more substituted carbon.
Final Step
Oxidation of Trialkylborane:
Treatment with hydrogen peroxide results in an oxygen insertion to convert boron compound into an alcohol.
Hydrolysis generates the final alcohol with anti-Markovnikov configuration.
Recognition of Reaction Conditions
Recognize hydroboration-oxidation conditions when given: alkene, borane, hydrogen peroxide.
Understand they lead to less substituted alcohol formation via anti-Markovnikov addition.
Summary
Hydroboration-oxidation is a controlled method for synthesizing alcohols from alkenes, allowing for tailored regio- and stereochemistry, especially to produce less substituted alcohols with defined configurations.
Hydroboration-Oxidation Reaction
The hydroboration-oxidation reaction is a method integral to organic chemistry for synthesizing alcohols from alkenes, characterized by its strict control over regioselectivity, resulting in an anti-Markovnikov addition process. This reaction is particularly valuable in the field of organic synthesis owing to its ability to produce less substituted alcohols, which are often more desirable in various chemical applications.
Key Properties
Anti-Markovnikov Addition: This reaction stands in stark contrast to other hydration methods, such as oxymercuration-demercuration, by favoring the addition of the hydroxyl group to the less substituted carbon of the alkene. This selectivity is crucial for synthesizing specific structural isomers that may have varied biological or chemical properties.
Goal: The primary aim is to generate less substituted alcohols, which can be useful in the development of pharmaceuticals and agrochemicals, where specific functional groups contribute to activity.
Mechanism Overview
Starting Materials: The reaction begins with an alkene and a hydroboration catalyst, most commonly borane (BH3). It is noteworthy that borane often exists primarily as a dimer (B2H6) and is usually solvated in non-polar solvents such as tetrahydrofuran (THF) or dimethyl sulfoxide (DMSO).
Initial Reaction: The process initiates with the addition of BH3 across the double bond of the alkene, leading to the formation of an organoborane intermediate.
Example: For instance, when methylcyclopentene undergoes hydroboration, the resulting organoborane structure will have the hydroxyl group strategically positioned on the less substituted carbon.
Orientation: The resulting addition presents a syn configuration, where H and OH addition occurs on the same side of the double bond.
Detailed Mechanism Steps
Step 1: The reaction starts with the overlap of the pi bond from the alkene with the empty p orbital of boron, which allows for electron density donation. This interaction creates a partial positive charge on the more substituted carbon atom, leading to the instability of the double bond.
Step 2: Subsequently, boron shifts to interact with the hydrogen from a hydrogen source (often part of a solvent) resulting in a transition state. In this transition state, the boron atom is selectively positioned on the less substituted carbon, confirming the anti-Markovnikov outcome.
Example Reaction
In a typical reaction scenario, a 99:1 ratio may favor anti-Markovnikov addition, ensuring the product configuration with boron bonded to the less substituted carbon and hydrogen attached to the more substituted carbon. This selectivity is pivotal, as it determines the functionality of the resultant alcohol.
Final Step: Oxidation of Trialkylborane
The final step entails the oxidation of trialkylborane through treatment with hydrogen peroxide (H2O2) in a basic medium (often using sodium hydroxide). This step results in the formation of an alcohol, with OH fully replacing the boron in the molecule. Hydrolysis further resolves the remaining organoborane to generate the final alcohol product, manifesting the anti-Markovnikov configuration.
Recognition of Reaction Conditions
It is essential to recognize hydroboration-oxidation conditions, which are typically characterized by the presence of an alkene, borane, and hydrogen peroxide. Understanding these conditions allows chemists to predict and manipulate the formation of less substituted alcohols through the anti-Markovnikov addition pathway effectively.
Summary
In summary, the hydroboration-oxidation reaction is a highly controlled method for synthesizing alcohols from alkenes, allowing for tailored regio- and stereochemistry outcomes. It excels at producing less substituted alcohols with defined configurations, making it an indispensable tool in both synthetic organic chemistry and industrial applications.