Chapter 6: Reactions of Alkenes and Stereochemistry of Addition Reactions

Overview of Alkene Addition Reactions

Alkenes undergo a variety of addition reactions, where reagents add across the carbon-carbon double bond. The stereochemistry and regiochemistry of these reactions are central to understanding their mechanisms and outcomes.

• Electrophilic Addition: Most alkene reactions proceed via electrophilic addition mechanisms.

• Key Products: Alcohols, halohydrins, dihalides, diols, epoxides, cyclopropanes, and carbonyl compounds.

• Reagents: HX, X2, H2O/H+, CH3OH/H+, Hg(OAc)2, BH3, peroxyacids, H2 (with catalyst).

Electrophilic Addition Mechanism

Electrophilic addition involves the breaking of the alkene π bond and the reagent σ bond, forming two new σ bonds. The sp2 carbons in the alkene become sp3 in the product.

• General Reaction:

• Examples of X-Y: H-Br, H-Cl, H-H, H-OH

Regioselectivity and Markovnikov's Rule

Regioselectivity refers to the preference for forming one constitutional isomer over another. Markovnikov's Rule predicts the orientation of addition in reactions of HX to alkenes.

• Markovnikov's Rule: In the addition of HX to an alkene, H attaches to the carbon with the most hydrogens, forming the more stable carbocation intermediate.

• Regioselective Reaction: More of one isomer is formed than another; can be moderate, high, or complete.

Example: Addition of HBr to propene forms 2-bromopropane exclusively, not 1-bromopropane.

Carbocation Stability

The stability of carbocation intermediates determines the major product in electrophilic addition reactions.

• Order of Stability: Tertiary (3°) > Secondary (2°) > Primary (1°) > Methyl

• Hyperconjugation: Stabilization by electron donation from adjacent σ bonds to the empty p orbital of the carbocation.

• Inductive Effects: Alkyl groups donate electron density, stabilizing the positive charge.

Carbocation Rearrangements

Carbocations can rearrange to form more stable intermediates via hydride or alkyl shifts.

• 1,2-Hydride Shift: Migration of a hydrogen atom with its electron pair.

• 1,2-Methyl Shift: Migration of a methyl group with its electron pair.

• Ring Expansion: Carbocation rearrangement can lead to ring expansion in cyclic systems.

Example: 2° carbocation rearranges to 3° via hydride shift.

Halogenation of Alkenes

Alkenes react with halogens (Br2, Cl2) to form vicinal dihalides via an anti addition mechanism.

• Mechanism: Formation of a cyclic halonium ion intermediate, followed by nucleophilic attack from the opposite face (anti addition).

• Stereochemistry: Only trans isomer is observed, not cis.

Halohydrin Formation

Halohydrins are formed when alkenes react with halogens in the presence of water.

• Mechanism: Similar to halogenation, but water acts as the nucleophile.

• Stereochemistry: Anti addition is observed.

• Regioselectivity: Halogen adds to the carbon with more hydrogens (Markovnikov rule).

Hydration of Alkenes

Hydration adds water across the double bond, forming alcohols. Industrially, this is catalyzed by acid.

• Mechanism: Carbocation intermediate, followed by nucleophilic attack by water.

• Regioselectivity: Markovnikov addition.

• Alcohol Addition: Using alcohol as nucleophile forms ethers via similar mechanism.

Oxymercuration-Demercuration

This method hydrates alkenes without carbocation rearrangement, using mercury(II) acetate and sodium borohydride.

• Advantages: No acidic conditions, no rearrangements.

• Regioselectivity: Markovnikov addition.

• Mechanism: Cyclic mercurinium ion intermediate, followed by reduction.

Hydroboration-Oxidation

Hydroboration-oxidation adds water across the double bond in an anti-Markovnikov fashion.

• Mechanism: Syn addition of borane, followed by oxidation to alcohol.

• Regioselectivity: H adds to the less substituted carbon.

• No Carbocation Rearrangement: Reaction proceeds via concerted mechanism.

Biological Alkene Hydration

Enzymes catalyze alkene hydration in biological systems, such as the conversion of fumaric acid to malic acid in the citric acid cycle.

• Enzyme: Fumarase

• Substrate Specificity: Only trans-fumaric acid is hydrated, not cis-maleic acid.

Alkene Epoxidation

Epoxidation forms epoxides by reaction with peroxyacids. The reaction is stereospecific and concerted.

• Mechanism: Cyclic transition state, retention of alkene stereochemistry.

• Reagents: Peroxyacids (e.g., mCPBA)

Summary Table: Alkene Addition Reactions

Stereochemistry of Addition Reactions

The stereochemistry of alkene addition reactions depends on the mechanism and the nature of the intermediate.

• Syn Addition: Both groups add to the same face (e.g., hydroboration, hydrogenation, epoxidation).

• Anti Addition: Groups add to opposite faces (e.g., halogenation, halohydrin formation).

• Stereoselective vs. Stereospecific: Stereoselective reactions favor one stereoisomer; stereospecific reactions give different products from different stereoisomeric reactants.

Key Concepts

• Electrophilic addition is the primary mechanism for alkene reactions.

• Carbocation stability (tertiary > secondary > primary) determines regioselectivity.

• Markovnikov's Rule predicts the major product in HX addition.

• Carbocation rearrangements (hydride/methyl shifts, ring expansion) can alter product structure.

• Halogenation and halohydrin formation proceed via anti addition due to cyclic intermediates.

• Hydration can be achieved by acid catalysis, oxymercuration-demercuration (avoids rearrangement), or hydroboration-oxidation (anti-Markovnikov, syn addition).

• Biological alkene hydration is enzyme-catalyzed and substrate-specific.

• Epoxidation is a stereospecific, concerted reaction with peroxyacids.