Ch 12 Alkene Concepts and Reactions

12-1 Electrophilic Addition

• Definition: Electrophilic addition involves the attack of an electron-deficient species (electrophile) on the electron-rich pi bond ($\pi$ bond) of an alkene. The double bond acts as a nucleophile, breaking the $\pi$ bond and forming new sigma bonds. This process typically proceeds through the formation of a carbocation or a bridged ion intermediate. Common reactants (electrophiles) include:

  • Hydrogen ($\text{H}-\text{H}$)

  • Water ($\text{H}-\text{OH}$)

  • Hydrogen halides ($\text{H}-\text{X}$ where X = F, Cl, Br, I)

  • Halogens ($\text{X}-\text{X}$ where X = Cl, Br)

A. Regioselective Reactions

• Regioselectivity: Refers to reactions where one of two or more possible constitutional (structural) isomers is predominantly formed. This is frequently governed by Markovnikov's Rule when dealing with unsymmetrical alkenes and unsymmetrical reagents.

  • Markovnikov's Rule: In the addition of H-X to an unsymmetrical alkene, the hydrogen atom of the reagent adds to the carbon atom of the double bond that already has more hydrogen atoms, while the halogen (or other electrophilic part of the reagent) adds to the carbon with fewer hydrogen atoms. This selectivity arises from the formation of the more stable carbocation intermediate (3^ ext{o} > 2^ ext{o} > 1^ ext{o}).

  • Example: When reactant X-Y adds to an unsymmetrical alkene with faces R[A] and R[B], regioselectivity occurs if the formation of X-A and Y-B is significantly favored over X-B and Y-A, or vice versa.

B. Stereoselective Reactions

• Stereoselective reactions: Reactions that preferentially form one stereoisomer over others. The outcome is determined by the reaction mechanism and the geometry of the transition state.

  • Types of Stereochemistry for Addition: When two new bonds are formed to the carbons originally involved in the double bond, the relative orientation can be:

    • Syn addition: Both parts of the adding molecule add to the same face (side) of the original double bond. For instance, in hydroboration-oxidation, both H and OH add syn.

    • Anti addition: The parts of the adding molecule add to opposite faces (sides) of the original double bond. Examples include halogenation and halo hydroxylation, where the halonium ion directs the subsequent attack from the opposite face.

  • Stereospecific reactions: These are a subset of stereoselective reactions where the stereochemistry of the reactant dictates the stereochemistry of the product. For example, a reaction might convert a cis-alkene exclusively into one pair of enantiomers and a trans-alkene into a different pair or a meso compound.

12-3 Hydrohalogenation

• Definition: Hydrohalogenation is the electrophilic addition of a hydrogen halide ($\text{H}-\text{X}$, where X = Cl, Br, I) to a carbon-carbon pi bond, forming an alkyl halide. The reaction typically follows Markovnikov's Rule.

• General Reaction:

  $\text{RCH}=\text{CHR}' + \text{H-X} \rightarrow \text{RCHX-CH}_2\text{R}' \text{ (Markovnikov product)}$

• Mechanism: This is a two-step ionic mechanism:

  1. Protonation: The alkene's $\pi$ electrons attack the electrophilic hydrogen of H-X, forming a $\sigma$ bond between one carbon of the alkene and hydrogen, and creating a carbocation intermediate on the other carbon. The more stable carbocation (3^ ext{o} > 2^ ext{o} > 1^ ext{o}) is preferentially formed. This step is often rate-determining.

  2. Nucleophilic Attack: The halide ion (X⁻), which is a nucleophile, rapidly attacks the carbocation to form the alkyl halide.

  • Rearrangements: Since carbocations are intermediates, rearrangements (e.g., hydride $(\text{H}^-)$ or alkyl $(\text{R}^-)$ shifts) can occur if a more stable carbocation can be formed, leading to a rearranged product.

12-4 Hydration

• Definition: Hydration is the acid-catalyzed addition of water ($\text{H}-\text{OH}$) to an alkene's pi bond, forming an alcohol. This reaction also follows Markovnikov's Rule.

• Conditions: The reaction requires an acid catalyst, typically dilute sulfuric acid ($\text{H}<em>2\text{SO}</em>4$) (e.g., 50% $\text{H}<em>2\text{SO}</em>4$) or concentrated $\text{H}<em>2\text{SO}</em>4$ followed by water. Using concentrated $\text{H}<em>2\text{SO}</em>4$ without sufficient water can lead to polymerization or elimination reactions.

• Mechanism: This mechanism closely parallels hydrohalogenation:

  1. Protonation: The alkene's $\pi$ electrons attack an electrophilic proton ($\text{H}^+$) from the acid catalyst, forming the most stable carbocation intermediate.

  2. Nucleophilic Attack: A water molecule (nucleophile) attacks the carbocation, forming an oxonium ion.

  3. Deprotonation: Another water molecule (or the conjugate base of the acid catalyst) deprotonates the oxonium ion, regenerating the acid catalyst and yielding the alcohol.

• Note on Rearrangement: Similar to hydrohalogenation, carbocation rearrangements (hydride or alkyl shifts) are possible and should be considered, leading to more stable product formation. Follows Markovnikov's Rule to ensure the hydroxyl group is placed on the more substituted carbon.

12-5 Halogenation

• Definition: Halogenation involves the addition of a dihalogen ($\text{X}2$, typically $\text{Br}</em>2$ or $\text{Cl}_2$) to a pi bond, resulting in the formation of a vicinal dihalide (halogens on adjacent carbons). The reaction occurs with anti-stereoselectivity.

• Mechanism: This reaction does not involve a free carbocation due to the formation of a unique bridged intermediate:

  1. Formation of a Bridged Halonium Ion: The alkene's $\pi$ electrons attack one of the halogen atoms, and the other halogen atom then forms a three-membered ring with the two carbons of the alkene, creating a cyclic halonium ion (e.g., bromonium ion or chloronium ion). This intermediate prevents rotation around the original double bond.

  2. Anti-Attack: A halide ion (X⁻) then attacks one of the carbons of the halonium ion from the opposite (anti) face, opening the ring and forming the vicinal dihalide.

• Stereochemistry: The anti-addition mechanism ensures that the two halogen atoms are added to opposite faces of the original double bond, which often leads to the generation of enantiomers or meso compounds depending on the alkene's structure.

12-6 Halo Hydroxylation

• Definition: Halo hydroxylation (or halohydrin formation) involves the addition of both a halogen atom (X) and a hydroxyl group (OH) across a double bond, forming a halohydrin. The reaction uses a halogen ($\text{X}_2$) in the presence of water as the solvent.

• Mechanism: The mechanism is similar to halogenation but water acts as the nucleophile:

  1. Halonium Ion Formation: The alkene reacts with $\text{X}_2$ to form a bridged halonium ion intermediate.

  2. Water Attack: Water (a nucleophile) attacks the more substituted carbon of the halonium ion ring (which carries a greater partial positive charge) from the anti-face. This step determines both the regiochemistry (OH on the more substituted carbon) and stereochemistry (anti-addition).

  3. Deprotonation: A subsequent deprotonation of the resulting oxonium ion by another water molecule yields the halohydrin.

• Stereospecific: This process is stereospecific, resulting in specific stereoisomer production, particularly anti-addition of the halogen and the hydroxyl group, forming a vicinal halohydrin.

12-7 Hydroboration-Oxidation

• Process: A highly regioselective (anti-Markovnikov) and stereoselective (syn-addition) two-step reaction sequence that converts an alkene into an alcohol.

• Mechanism:

  1. Hydroboration (Step 1): Borane ($\text{BH}<em>3$), often provided as a complex with tetrahydrofuran ($\text{BH}</em>3 \cdot \text{THF}$), adds to the alkene. This is a concerted syn-addition where both the hydrogen and the boron atoms add to the same face of the double bond. Boron preferentially adds to the less substituted carbon atom of the alkene ($\text{R} = \text{H}$) due to both steric hindrance (minimizing bulkier groups proximity) and electronic factors (boron acts as an electrophile, H acts as a hydride-like species). This results in the formation of an alkylborane (e.g., trialkylborane).

  2. Oxidation (Step 2): The alkylborane is then oxidized using hydrogen peroxide ($\text{H}2\text{O}2$) in aqueous sodium hydroxide ($\text{NaOH}$) solution. This step replaces the B-C bond with an O-C bond, with retention of configuration at the carbon that was originally bonded to boron. The net result is the anti-Markovnikov addition of water ($\text{H}$ to the more substituted carbon, $\text{OH}$$ to the less substituted carbon) with syn-stereochemistry, yielding an alcohol.

12-8 Radical Mechanisms and Reagents

• Context: While many alkene reactions discussed are ionic (electrophilic additions), some reactions proceed via radical mechanisms, particularly in the presence of peroxides or light (e.g., anti-Markovnikov addition of HBr to alkenes).

• Stages of Radical Reactions:

  • Initiation: Involves the homolytic cleavage of a bond to generate reactive radical species, typically by heat ($\Delta$) or light ($\text{h}\nu$).

  • Propagation: A radical reacts with a stable molecule to form a new stable molecule and a new radical, continuing the reaction chain. These reactions follow through stable radical intermediates.

  • Termination: Two radical species combine to form a stable, non-radical product, ending the propagation chain.

12-10 Epoxide Formation with MCPBA

• Definition: Epoxides (also known as oxiranes, three-membered cyclic ethers) are formed by the oxidation of alkenes using peroxyacids. The most common peroxyacid for this purpose is meta-chloroperoxybenzoic acid (MCPBA).

• Stages of Reaction:

  • Step 1: Epoxidation: The alkene reacts with a peroxyacid (like MCPBA) in a concerted, one-step process. The peroxyacid transfers an oxygen atom to the alkene's double bond to form the epoxide. This reaction is stereospecific; cis-alkenes give cis-epoxides and trans-alkenes give trans-epoxides, meaning the relative stereochemistry of substituents on the alkene is maintained in the epoxide.

  • Step 2: Hydrolysis of Epoxide (Anti-Dihydroxylation): Epoxides can subsequently be hydrolyzed (ring-opened with water) under acidic or basic conditions to yield vicinal diols (1,2-diols).

    • Acid-catalyzed hydrolysis: Protonation of the epoxide makes it more susceptible to nucleophilic attack. Water then attacks the more substituted carbon of the protonated epoxide from the anti-face, leading to a product with anti-stereochemistry.

    • Base-catalyzed hydrolysis: A hydroxide ion ($\text{OH}^-$) attacks the less substituted carbon of the epoxide ring from the anti-face, also leading to a diol with anti-stereochemistry.

    • This hydrolysis can create racemic mixtures of enantiomers or meso compounds, depending on the structure of the epoxide.

12-11 Anti-Dihydroxylation

• Process: This refers specifically to the two-step synthesis of vicinal diols where the two hydroxyl groups are added to opposite faces of the original double bond. The mechanism involves:

  1. Epoxidation: An alkene is first converted to an epoxide (e.g., using MCPBA).

  2. Ring-opening Hydrolysis: The epoxide is then opened by acidic water ($\text{H}_3\text{O}^+$) or basic water ($\text{OH}^-, H₂O). The nucleophilic attack (by water in acidic conditions, or hydroxide in basic conditions) occurs from the anti-face relative to the oxygen bridge of the epoxide. This effectively generates two hydroxyl groups on different sides of the molecule (anti-addition).

12-12 Ozonolysis

• Definition: Ozonolysis is a powerful reaction used to cleave carbon-carbon double bonds ($\text{C}=\text{C}$) or triple bonds by reaction with ozone ($\text{O}_3$), a highly reactive electrophilic allotrope of oxygen. The reaction is valuable for determining the position of double bonds in unknown compounds and for synthesizing aldehydes, ketones, and carboxylic acids.

• Mechanism: This reaction proceeds through several stages:

  1. Initial Cycloaddition: Ozone undergoes a concerted 1,3-dipolar cycloaddition with the alkene to form an unstable intermediate known as a primary ozonide (or molozonide).

  2. Retro-1,3-Dipolar Cycloaddition (Rearrangement): The primary ozonide quickly rearranges by cycloreversion to form a carbonyl compound (aldehyde or ketone) and a carbonyl oxide.

  3. Final Cycloaddition: The carbonyl oxide and the carbonyl compound then recombine in a subsequent 1,3-dipolar cycloaddition to form a more stable, cyclic secondary ozonide.

• Workup: The ozonide intermediate is generally not isolated but is cleaved in a second step, known as the workup:

  • Reductive Workup: Using reducing agents like zinc metal and acetic acid ($\text{Zn}/\text{CH}<em>3\text{COOH}$), dimethyl sulfide ($\text{DMS}$), or triphenylphosphine ($\text{PPh}</em>3$) breaks the ozonide to yield aldehydes and ketones (if hydrogens are present on the double bond carbons) without further oxidation.

  • Oxidative Workup: Using oxidizing agents like hydrogen peroxide ($\text{H}2\text{O}2$) will break the ozonide and further oxidize any aldehydes formed into carboxylic acids, while ketones remain as ketones.

Important Notes

• Consistently apply Markovnikov's Rule during reactions involving unsymmetrical double bonds (e.g., hydrohalogenation, hydration, halohydrin formation). Remember that this rule is fundamentally driven by the stability of carbocation intermediates or partial positive charges developed during the transition state (3^ ext{o} > 2^ ext{o} > 1^ ext{o}).

• Recognize the potential for carbocation rearrangements to occur in reactions that proceed through carbocation intermediates (like hydrohalogenation and hydration). These rearrangements (1,2-hydride or 1,2-alkyl shifts) lead to a more stable carbocation, resulting in different or unexpected product structures.

• Understand the implications of stereochemistry in product formation, especially during syn and anti additions. The specific mechanism of each reaction dictates whether the new groups add to the same face or opposite faces of the original double bond, which is crucial for predicting the stereochemical outcome (enantiomers, diastereomers, or meso compounds).