Organic Chemistry III - Chapter 8: Reactions of Alkenes

• Alkenes undergo addition reactions, where reagents add across the double bond, resulting in saturated compounds.

These reactions can involve various types of reagents, including halogens, hydrogen halides, and water, thereby enabling the synthesis of alcohols, alkyl halides, and other functional groups.

Chapter 8: Reactions of Alkenes

Reactivity of the Carbon–Carbon Double Bond

• Most common reactions of double bonds involve breaking the pi ($\pi$) bond, leaving the sigma ($\sigma$) bond intact.

Types of Alkene Reactions

• Addition: A molecule X-Y adds across the double bond to form a single bond with two new groups attached: $\text{C=C} + \text{X-Y} \rightarrow \text{-C(X)-C(Y)-}$.

• Elimination: Opposite of addition; typically forms an alkene from a saturated compound.

• Substitution: One atom or group is replaced by another.

Bonding in Alkenes and Electrophilic Addition

• Pi ($\pi$) electrons: These electrons in pi bonds are loosely held.

• Nucleophilic Nature: The double bond acts as a nucleophile, attacking electrophilic species ($\text{E}^+$).

• Carbocation Intermediates: Carbocations ($\text{C}^+$) are formed as intermediates in some of these reactions.

  • They feature an empty p orbital on the positively charged carbon.

• Reaction Type: These reactions are called electrophilic additions.

Mechanism of Electrophilic Addition

• Step 1: Attack of the pi bond on the electrophile ($\text{E}^+$) forms a carbocation ($\text{C}^+$).

  • $\text{C=C} + \text{E}^+ \rightarrow \text{-C(E)-C}^+$ (The positive charge is on the more substituted carbon, if applicable).

• Step 2: Attack by a nucleophile ($\text{Nuc}:$) on the carbocation gives the addition product.

  • $\text{-C(E)-C}^+ + \text{Nuc}: \rightarrow \text{-C(E)-C(Nuc)-}$

Types of Additions to Alkenes

Addition of HX to Alkenes (Hydrohalogenation)

• $\text{HBr}$, $\text{HCl}$, and $\text{HI}$ can be added via this reaction.

Mechanism

1. Step 1 (Protonation): The double bond is protonated by HX, forming the most stable carbocation possible.

   • This is the rate-determining step.

2. Step 2 (Nucleophilic Attack): The halide nucleophile ($\text{X}^-$) attacks the carbocation, forming an alkyl halide.

Regioselectivity: Markovnikov's Rule

• Original Rule: The addition of a proton to the double bond of an alkene results in a product with the acidic proton bonded to the carbon atom that already holds the greater number of hydrogens.

• Extended Rule: In an electrophilic addition to an alkene, the electrophile adds in such a way that it generates the most stable intermediate (carbocation).

  • For example, in $\text{CH}<em>3\text{-C(CH}</em>3\text{)=CH-CH}_3$, the acid proton will bond to carbon #3 (least substituted) to produce the more stable tertiary carbocation at carbon #2.

  • The bromide anion then adds to this carbocation.

Reaction-Energy Diagram

• Step 1 (formation of carbocation) is the rate-determining step.

• Formation of a more stable secondary ($2^o$) carbocation (lower energy transition state) leads to the major (Markovnikov) product.

• Formation of a less stable primary ($1^o$) carbocation (higher energy transition state) leads to a minor product.

Examples

• $\text{CH}<em>3\text{-CH=CH}</em>2 + \text{HBr} \rightarrow \text{CH}<em>3\text{-CH(Br)-CH}</em>3$ (Markovnikov product).

• $\text{CH}<em>3\text{-C(CH}</em>3\text{)=CH-CH}<em>2\text{CH}</em>3 + \text{HCl} \rightarrow \text{CH}<em>3\text{-C(CH}</em>3\text{)(Cl)-CH}<em>2\text{CH}</em>2\text{CH}_3$ (Markovnikov product).

Carbocation Rearrangements

• Free-Radical Mechanism

1. Initiation:

   • The peroxide bond breaks homolytically to form two alkoxyl radicals: $\text{RO-OR} \rightarrow 2\text{RO}$•

   • A hydrogen atom is abstracted from $\text{HBr}$ by the alkoxyl radical to form a bromine radical: $\text{RO}$•$+\text{H-Br} \rightarrow \text{ROH} + \text{Br}$•

2. Propagation Steps:

   • Bromine addition: The bromine radical ($\text{Br}$•) adds to the double bond, forming the most stable alkyl radical possible (e.g., tertiary radical over secondary).

     • The addition of the bromine radical is regioselective, leading to the anti-Markovnikov outcome.

   • Hydrogen abstraction: Hydrogen is abstracted from another molecule of $\text{HBr}$ by the new alkyl radical, forming the final anti-Markovnikov alkyl bromide product and regenerating a bromine radical to continue the chain.

Anti-Markovnikov Regioselectivity

• The intermediate tertiary radical forms faster and is more stable than a secondary radical.

  • Example: $\text{CH}<em>3\text{-C(CH}</em>3\text{)=CH-CH}<em>3 + \text{Br}$• $\rightarrow$ $\text{CH}</em>3\text{-C(CH}<em>3\text{)-CH(Br)-CH}</em>3$ (tertiary radical, more stable).

  • This is in contrast to the electrophilic addition where the carbocation forms on the more substituted carbon.

Hydration of Alkenes (Acid-Catalyzed)

• Reaction: Addition of water to an alkene forms an alcohol.

• Reversibility: This is the reverse of the dehydration of alcohols.

• Conditions: Use very dilute solutions of $\text{H}<em>2\text{SO}</em>4$ or $\text{H}<em>3\text{PO}</em>4$ to drive the equilibrium toward hydration (alcohol formation).

Mechanism of Hydration

1. Step 1 (Protonation): Protonation of the double bond (by $\text{H}_3\text{O}^+$) forms a carbocation. This step follows Markovnikov's rule – the proton adds to the less substituted carbon, placing the positive charge on the more substituted (and thus more stable) carbon.

2. Step 2 (Nucleophilic Attack): Water (nucleophile) attacks the carbocation.

3. Step 3 (Deprotonation): Deprotonation of the oxygen atom (by another water molecule) yields the final alcohol product and regenerates $H_3O^+$ catalyst.

Orientation of Hydration

• The protonation follows Markovnikov’s rule.

• The proton adds to the less substituted end of the double bond, so the positive charge appears at the more substituted end (generating the most stable carbocation).

Rearrangements

• Carbocation rearrangements (e.g., methyl shifts or hydride shifts) are possible in acid-catalyzed hydration, similar to HX addition, leading to rearranged products.

  • Example: Hydration of 3,3-dimethylbut-1-ene can lead to a methyl shift from a $2^o$ carbocation to a $3^o$ carbocation, forming 2,3-dimethylbutan-2-ol as the major product.

Indirect Hydration Methods

1. Oxymercuration-Demercuration

• Overall: Markovnikov addition of water ($\text{H-OH}$) to the double bond.

• Conditions: Milder than direct acid-catalyzed hydration.

• Key Features:

  • Markovnikov product formed.

  • Anti addition of H and OH (meaning H and OH add to opposite faces of the double bond).

  • No rearrangements or polymerization.

Oxymercuration Step

1. Electrophile Formation: Mercury(II) acetate ($\text{Hg(OAc)}_2$) dissociates slightly to form the electrophile $\,^+ \text{Hg(OAc)}$.

2. Attack and Cyclic Ion Formation: $\,^+ \text{Hg(OAc)}$ attacks the pi bond, forming a cyclic mercurinium ion (a three-membered ring system with a positive charge, analogous to a halonium ion).

3. Nucleophilic Attack: Water approaches the mercurinium ion from the side opposite the ring (anti addition).

4. Regioselectivity: Water adds to the more substituted carbon of the mercurinium ion, leading to the Markovnikov orientation.

   • This forms an organomercurial alcohol intermediate.

Demercuration Step

• Reagent: Sodium borohydride ($\text{NaBH}_4$), a reducing agent, furnishes a hydride ion ($\text{H}^-$).

• Reaction: The hydride ion replaces the mercuric acetate ($\text{-HgOAc}$) group.

• Overall Product: The overall reaction gives the Markovnikov product with the hydroxy group on the most substituted carbon.

  • $\text{C-C(OH)-C(HgOAc)-} + \text{NaBH}<em>4 \rightarrow \text{C-C(OH)-C(H)-} + \text{Hg} + \text{NaB(OH)}</em>4 + \text{OAc}^-$

Alkoxymercuration-Demercuration

• If an alcohol ($\text{ROH}$) is used as the nucleophile instead of water ($\text{HOH}$), the product is an ether ($\text{R-O-C-C-H}$).

2. Hydroboration-Oxidation

• Overall: Anti-Markovnikov addition of water ($\text{H-OH}$) to the double bond.

• Key Features:

  • Anti-Markovnikov product formed.

  • Syn addition of H and OH (meaning H and OH add to the same face of the double bond).

• Borane Reagent: Borane ($\text{BH}<em>3$) is typically used in a complex with tetrahydrofuran (THF) to stabilize it (e.g., $ext{BH}</em>3$\text{•}\text{THF}). Borane exists as a dimer, $ext{B}<em>2 ext{H}</em>6$.

Hydroboration Step (Addition of Borane)

1. Reaction: The electron-deficient borane adds across the double bond.

2. Regioselectivity: Borane adds its hydrogen to the more substituted carbon, and the boron atom adds to the least-substituted carbon ($\text{C}^+$ character on adjacent carbon).

3. Stereochemistry: The hydrogen and the boron add to the same side of the double bond (syn addition).

4. Stoichiometry: Three moles of alkene can react with each mole of $\text{BH}<em>3$, forming a trialkylborane ($\text{(R}</em>3\text{B)}$).

   • $\text{3 R-CH=CH}<em>2 + \text{BH}</em>3 \rightarrow \text{(R-CH}<em>2\text{-CH}</em>2\text{)}_3\text{B}$

Oxidation Step

1. Reagents: Oxidation of the alkylborane with basic hydrogen peroxide ($\text{H}<em>2\text{O}</em>2\text{, OH}^-$).

2. Product: This produces the alcohol with anti-Markovnikov orientation.

3. Stereochemistry: The $\text{OH}$ group replaces the boron atom, maintaining the same stereochemical orientation (syn addition is preserved).

   • Mechanism: Involves the formation of a hydroperoxide ion ($\text{HOO}^-$), followed by attack on boron, migration of the alkyl group, and finally hydrolysis of the borate ester to release the alcohol and borate ions.

Addition of Halogens to Alkenes (Halogenation)

• Reagents: $\text{Cl}<em>2$, $\text{Br}</em>2$, and sometimes $\text{I}_2$.

• Products: Add to a double bond to form a vicinal dihalide (halogens on adjacent carbons).

• Conditions: Solvent like $\text{CCl}_4$ (non-polar).

• Stereospecificity: Anti addition is observed, meaning the two halogen atoms add to opposite faces of the double bond.

Mechanism

1. Step 1 (Halonium Ion Formation): The alkene attacks the halogen molecule, forming a cyclic halonium ion ($\text{X}^+$ bridged-ring structure, e.g., bromonium ion).

   • A halide ion ($\text{X}^-$) is also released.

2. Step 2 (Opening of Halonium Ion): The halide ion ($\text{X}^-$) attacks the halonium ion from the back side (SN2-like attack), opening the ring and resulting in anti addition.

   • This attack is regioselective; if the halonium ion is unsymmetrical, the halide attacks the more substituted carbon.

Stereospecific Reactions

• A reaction is stereospecific when a specific stereoisomer of the reactant reacts to give a specific stereoisomeric form of the product.

  • Example: cis-2-Butene + $\text{Br}_2 \rightarrow$ Enantiomeric pair (racemate of anti-dibromobutane).

  • Example: trans-2-Butene + $\text{Br}_2 \rightarrow$ Meso stereoisomer (anti-dibromobutane with a plane of symmetry).

Bromine Test for Unsaturation

• An alkene rapidly decolorizes a dark, red-brown solution of $\text{Br}<em>2$ in $\text{CCl}</em>4$. The color disappears as bromine adds across the double bond.

• This is a chemical test for the presence of carbon-carbon double (or triple) bonds.

Formation of Halohydrins

• Conditions: If a halogen is added to an alkene in the presence of water.

• Product: A halohydrin is formed (an alcohol with a halogen on an adjacent carbon).

• Nucleophile: Water acts as the nucleophile, instead of the halide ion.

• Orientation: Product is Markovnikov (OH on the more substituted carbon, X on the less substituted carbon).

• Stereochemistry: Anti addition is observed.

Mechanism of Halohydrin Formation

1. Halonium Ion Formation: Similar to halogenation, the alkene attacks the halogen, forming a cyclic halonium ion and releasing a halide ion.

2. Nucleophilic Attack by Water: Water (a stronger nucleophile and present in high concentration) attacks the halonium ion from the back side.

   • Regiospecificity: Water preferentially attacks the most highly substituted carbon of the halonium ion because that carbon carries more partial positive charge.

3. Deprotonation: A water molecule deprotonates the oxygen, yielding the halohydrin and regenerating $H_3O^+$ .

Stereochemistry and Regiospecificity

• Anti stereochemistry: Due to the backside attack on the halonium ion.

• Markovnikov orientation: The nucleophile (water) adds to the more substituted carbon with the greater positive charge, and the halogen adds to the less substituted carbon.

Catalytic Hydrogenation of Alkenes

• Reaction: Hydrogen ($\text{H}_2$) is added across the double bond, converting an alkene to an alkane.

• Catalyst Requirement: The reaction only occurs in the presence of a catalyst (e.g., Pt, Pd, Ni, Rh).

• Wilkinson’s Catalyst: A soluble homogeneous catalyst ($\text{RhCl(PPh}<em>3\text{)}</em>3$) that catalyzes the hydrogenation of carbon-carbon double bonds.

Mechanism of Heterogeneous Catalytic Hydrogenation

1. Adsorption: Both the hydrogen gas and the alkene are adsorbed onto the metal surface of the catalyst.

2. Insertion/Addition: Once adsorbed, the hydrogen atoms insert (add) across the same face of the double bond.

3. Release: The reduced product (alkane) is then released from the metal surface.

Syn Stereochemistry

• Due to the simultaneous addition of both hydrogen atoms to the same side of the double bond on the catalyst surface, the reaction has syn stereochemistry.

Need for Chiral Catalysts

• In some cases, specific enantiomers are required for biological activity (e.g., only the ($-$)-enantiomer of DOPA can cross the blood-brain barrier and be transformed into dopamine; the other enantiomer is toxic).

• Chiral catalysts are developed to produce a single enantiomer selectively.

Epoxidation

• Reaction: Alkenes react with a peroxyacid ($\text{RCO}_3\text{H}$) to form an epoxide (also called an oxirane, which is a three-membered cyclic ether).

• Common Reagent: m-chloroperoxybenzoic acid (MCPBA) is a usual reagent.

• General Reaction:
  $\text{C=C} + \text{R-C(=O)-O-OH} \rightarrow \text{C(O)C} + \text{R-C(=O)-OH}$

Mechanism

• The reaction takes place in a single, concerted step.

• Bond cleavage and bond formation occur simultaneously in a cyclic transition state.

Stereochemistry of Epoxidation

• Epoxidation is stereospecific.

• The cis or trans stereochemistry of the alkene is maintained in the epoxide product.

  • A cis-alkene yields a cis-epoxide.

  • A trans-alkene yields a trans-epoxide.

Opening the Epoxide Ring (Acid-Catalyzed Hydrolysis)

• Reactivity: The highly strained three-membered ring of epoxides makes them much more reactive than other ethers.

• Acid-Catalyzed (with water):

  1. The epoxide oxygen is protonated by an acid ($\text{H}_3\text{O}^+$).

  2. Water acts as a nucleophile and attacks the protonated epoxide from the back side (anti-attack) at the more substituted carbon.

  3. Deprotonation yields a trans-diol (glycol).

One-Step Synthesis of Diols

• To synthesize the glycol without isolating the epoxide, aqueous peroxyacetic acid or peroxyformic acid can be used.

• The reaction remains stereospecific, yielding anti-diols.

Syn Hydroxylation of Alkenes

• Reaction: Converts an alkene to a syn-1,2-diol (both hydroxyl groups add to the same face of the original double bond).

• Reagents:

  1. Osmium tetroxide ($\text{OsO}<em>4$) followed by hydrogen peroxide ($\text{H}</em>2\text{O}<em>2$) or sodium bisulfite ($\text{NaHSO}</em>3$).

  2. Cold, dilute solution of potassium permanganate ($\text{KMnO}_4$) in base.

Mechanism with OsO4

1. $\text{OsO}_4$ adds to the double bond of an alkene in a concerted mechanism, forming a cyclic osmate ester.

2. The osmate ester is then hydrolyzed (cleaved) to produce a cis-glycol and regenerate the $\text{OsO}_4$ catalyst.

Permanganate Dihydroxylation

• A cold, dilute, basic solution of $\text{KMnO}_4$ also hydroxylates alkenes with syn stereochemistry.

• Mechanism: $\text{KMnO}_4$ forms a cyclic manganate ester, which is then hydrolyzed by the basic solution.

• Products: This liberates the glycol and produces a brown precipitate of manganese dioxide ($\text{MnO}_2$), which is an indicator for the reaction.

Stereospecificity of Syn Hydroxylation

• If a chiral carbon is formed, only one stereoisomer (or a pair of enantiomers) will be produced, depending on the starting alkene.

  • Example: cis-3-Hexene + $\text{OsO}<em>4$ then $\text{H}</em>2\text{O}_2 \rightarrow$ meso-3,4-hexanediol.

  • Example: cis-2-Butene + $\text{KMnO}_4$ (cold, dilute, basic) $\rightarrow$ Enantiomeric pair of 2,3-butanediol.

  • Example: trans-2-Butene + $\text{KMnO}_4$ (cold, dilute, basic) $\rightarrow$ meso-2,3-butanediol.

Oxidative Cleavage

• Reaction: Both the pi ($\pi$) and sigma ($\sigma$) bonds of the double bond break.

• Outcome: The carbon-carbon double bond ($\text{C=C}$) becomes two carbon-oxygen double bonds ($\text{C=O}$).

• Products: Ketones, carboxylic acids, or even carbon dioxide ($\text{CO}_2$) may be obtained, depending on the method and substitution pattern of the alkene.

• Application: Used to determine the position of a double bond in an unknown alkene.

1. Cleavage with Warm or Concentrated or Acidic Potassium Permanganate ($\text{KMnO}_4$)

• Reagent: Permanganate is a strong oxidizing agent.

• Mechanism: The glycol initially formed is further oxidized.

• Product Determination:

  • Disubstituted carbons (attached to two other carbons) become ketones.

  • Monosubstituted carbons (attached to one other carbon and a hydrogen) become carboxylic acids.

  • Terminal =$\text{CH}<em>2$ groups become carbon dioxide ($\text{CO}</em>2$).

2. Ozonolysis

• Reagent: Ozone ($\text{O}_3$).

• Outcome: Ozone will oxidatively cleave (break) the double bond to produce aldehydes and ketones.

• Mildness: Ozonolysis is milder than $ext{KMnO}_4$ and will not oxidize aldehydes further to carboxylic acids.

• Two-Step Process:

  1. Reaction with Ozone: The alkene reacts with ozone to form an unstable molozonide, which quickly rearranges to form a more stable cyclic ozonide intermediate.

  2. Reduction of Ozonide: The ozonide is not isolated but is treated with a mild reducing agent.

     • Common Reducing Agents: Zinc ($\text{Zn}$) in water or acetic acid, or dimethyl sulfide ($\text{Me}_2\text{S}$).

     • Products: Yields aldehydes and/or ketones.

     • When dimethyl sulfide is used, the sulfur atom is oxidized, forming dimethyl sulfoxide ($\text{DMSO}$).

Comparison: Permanganate Cleavage vs. Ozonolysis

Determining Alkene Structure via Oxidative Cleavage

• By identifying the carbonyl products (ketones and aldehydes) from ozonolysis, the original structure of the alkene can be deduced by effectively