Premed · Premed · Organic Chemistry 1
Lecture 14: Alkene Reactions: Hydration, Hydroboration, Halogenation
Organic Chemistry I
Learning Objectives
By the end of this lecture, students will be able to:
- Describe the hydroboration-oxidation reaction and its anti-Markovnikov, syn selectivity
- Explain halogenation (Br2, Cl2) of alkenes through halonium ion intermediates
- Predict the stereochemistry (syn vs. anti) of various addition reactions
- Describe halohydrin formation and its mechanism
- Explain catalytic hydrogenation as a syn addition
- Describe oxidative cleavage reactions (ozonolysis, permanganate)
- Explain epoxidation of alkenes and its synthetic utility
- Summarize the complete toolkit of alkene reactions with regiochemistry and stereochemistry
Lecture Content
I. Hydroboration-Oxidation
Hydroboration-oxidation converts an alkene to an alcohol with anti-Markovnikov regiochemistry and syn stereochemistry. In the first step, borane (BH3 or BH3-THF) adds to the alkene through a concerted, four-membered transition state in which boron and hydrogen are delivered simultaneously to the same face of the double bond. Boron, acting as an electrophilic Lewis acid with its empty p orbital, adds to the less substituted carbon (guided by steric preferences), while hydrogen adds to the more substituted carbon. Because there is no carbocation intermediate, rearrangements cannot occur.
In the second step, oxidation with hydrogen peroxide and sodium hydroxide replaces the boron with a hydroxyl group, with retention of configuration at the carbon. The net result places OH on the less substituted carbon (anti-Markovnikov) with both groups delivered from the same face (syn addition). This reaction is complementary to acid-catalyzed hydration and oxymercuration, which both give Markovnikov products.
<image>Panel A: The complete hydroboration-oxidation of 1-methylcyclohexene. Step 1 shows BH3 approaching the less hindered face of the double bond with a concerted four-membered transition state (B---C---C---H), producing the organoborane with B and H both on the same face (syn). Step 2 shows oxidation with H2O2/NaOH replacing B with OH (retention), giving trans-2-methylcyclohexanol as the product. Panel B: Comparison of regiochemistry: acid-catalyzed hydration of propene gives 2-propanol (Markovnikov), while hydroboration-oxidation gives 1-propanol (anti-Markovnikov). Both reactions shown with their products highlighted.</image>
II. Halogenation of Alkenes
The addition of Br2 or Cl2 to alkenes produces vicinal dihalides (1,2-dihalides) through a mechanism involving a cyclic halonium ion intermediate. In the first step, the pi electrons of the alkene attack the electrophilic halogen, forming a three-membered cyclic halonium ion (a bromonium or chloronium ion) rather than an open carbocation. The halogen bridges both carbons of the former double bond, preventing rotation and controlling stereochemistry. In the second step, the halide ion attacks the halonium ion from the opposite face through an SN2-like ring opening, preferentially at the more substituted carbon in unsymmetrical cases.
The stereochemical outcome is strict anti addition: the two halogen atoms end up on opposite faces of the original double bond. The reaction of cyclohexene with Br2, for example, produces exclusively trans-1,2-dibromocyclohexane. Depending on the symmetry of the alkene, the products may be meso, racemic, or a single enantiomer. The existence of the bromonium ion has been confirmed experimentally by George Olah, and it explains the strict anti stereochemistry that would be impossible with an open carbocation intermediate.
III. Halohydrin Formation
When halogenation is performed in water rather than in an inert solvent, a halohydrin forms instead of a dihalide. The mechanism begins identically, with formation of the halonium ion. However, since water is present in large excess as the solvent, it outcompetes the halide ion as the nucleophile and attacks the more substituted carbon of the halonium ion (which is more electrophilic) from the opposite face. After deprotonation of the resulting oxonium ion, the product is a halohydrin with the halogen on the less substituted carbon and the hydroxyl on the more substituted carbon, with anti stereochemistry.
Halohydrins are valuable synthetic intermediates because treatment with base induces an intramolecular SN2 reaction that forms an epoxide, linking this chemistry directly to the epoxide reactions discussed in Lecture 18.
IV. Catalytic Hydrogenation
Catalytic hydrogenation adds molecular hydrogen (H2) across a double bond in the presence of a metal catalyst, completely saturating the alkene. Common catalysts include palladium on carbon (Pd/C), platinum oxide (PtO2, Adam's catalyst), and Raney nickel. The mechanism involves heterogeneous catalysis: both the alkene and H2 adsorb onto the metal surface, the H2 molecule dissociates into individual hydrogen atoms on the surface, and both atoms are delivered to the same face of the adsorbed alkene. The product then desorbs.
The stereochemical consequence is syn addition: both hydrogens add to the same face of the double bond. Hydrogenation of 1,2-dimethylcyclohexene, for example, gives cis-1,2-dimethylcyclohexane. The heat of hydrogenation, which measures how much energy is released, provides a quantitative measure of alkene stability: less negative values indicate a more stable starting alkene.
<image>Panel A: Catalytic hydrogenation of 1,2-dimethylcyclohexene on a palladium surface. The alkene adsorbs flat on the metal surface, H2 molecules dissociate into H atoms on the surface, and both H atoms are delivered to the bottom face (the face touching the catalyst), producing cis-1,2-dimethylcyclohexane. The 3D structure of the product is shown with both methyl groups and both new H atoms on the same face. Panel B: A summary of conditions showing Pd/C, H2 (1 atm), EtOH as solvent, room temperature, producing the saturated product.</image>
V. Epoxidation
Epoxidation converts an alkene to an epoxide (oxirane) using a peroxy acid. Common reagents include mCPBA (meta-chloroperoxybenzoic acid), peracetic acid, and MMPP. The mechanism is a concerted "butterfly" process in which the peroxy acid delivers an oxygen atom to the alkene as its O-O bond breaks and the new C-O bonds form, all through a single transition state with no intermediate.
The stereochemistry is syn addition: the oxygen atom adds to one face of the double bond, and both new C-O bonds are formed on the same side. As a result, cis alkenes give cis epoxides and trans alkenes give trans epoxides. Epoxides are extraordinarily useful synthetic intermediates because their strained three-membered ring is readily opened by nucleophiles, producing 1,2-difunctionalized products with anti stereochemistry in the ring-opening step. Epoxide ring opening can be performed under either acidic or basic conditions.
VI. Oxidative Cleavage: Ozonolysis
Ozonolysis cleaves the carbon-carbon double bond entirely, producing two carbonyl compounds. The reaction involves two steps: treatment with ozone (O3) in dichloromethane at -78 degrees C forms an ozonide intermediate, and the subsequent workup determines the final products. Reductive workup with zinc/acetic acid or dimethyl sulfide gives aldehydes and/or ketones, while oxidative workup with hydrogen peroxide converts any aldehydes to carboxylic acids (ketones remain unchanged).
To predict the products, consider that each carbon of the original double bond becomes a carbonyl carbon (C=O). If a carbon carried one hydrogen, it becomes an aldehyde (or carboxylic acid with oxidative workup). If it carried no hydrogens, it becomes a ketone. If it carried two hydrogens, it becomes formaldehyde (or formic acid). Ozonolysis is useful both for structure determination (identifying the position of a double bond by analyzing the carbonyl fragments) and for synthesis.
VII. Dihydroxylation
Syn-dihydroxylation adds two hydroxyl groups to the same face of the double bond, producing a cis-1,2-diol (vicinal diol). Osmium tetroxide (OsO4) achieves this through a concerted [3+2] cycloaddition that forms an osmate ester intermediate, which is then hydrolyzed. OsO4 can be used catalytically with a co-oxidant such as NMO or potassium ferricyanide. Cold, dilute, basic potassium permanganate (KMnO4) produces the same syn-dihydroxylation result.
Anti-dihydroxylation, giving a trans-1,2-diol, is accomplished indirectly by first epoxidizing the alkene and then opening the epoxide under acidic conditions. Hot, concentrated, acidic KMnO4 goes beyond dihydroxylation to perform complete oxidative cleavage of the double bond, producing carboxylic acids and ketones in a transformation analogous to ozonolysis with oxidative workup.
VIII. Summary: Alkene Reaction Toolkit
The complete set of alkene reactions provides a versatile synthetic toolkit. Markovnikov additions include HX (giving alkyl halides through a carbocation with no stereoselectivity), acid-catalyzed hydration (Markovnikov alcohol with rearrangement risk), and oxymercuration-demercuration (Markovnikov alcohol without rearrangement). Anti-Markovnikov additions include hydroboration-oxidation (anti-Markovnikov alcohol with syn addition) and radical HBr addition with peroxides (anti-Markovnikov bromide, covered in Lecture 16).
Halogenation with X2 gives vicinal dihalides through anti addition, while X2 in water produces halohydrins, also with anti addition. Catalytic hydrogenation with H2/Pd delivers the fully saturated product through syn addition. Oxidation reactions include epoxidation with mCPBA (syn), syn-dihydroxylation with OsO4, and oxidative cleavage through ozonolysis or hot KMnO4.
<image>A comprehensive reaction map with an alkene (C=C) drawn in the center and arrows radiating outward to all possible products. Each arrow is labeled with the reagent(s) and conditions. Products shown include: Markovnikov alcohol (H3O+ or Hg(OAc)2/NaBH4), anti-Markovnikov alcohol (BH3/H2O2), alkyl halide (HX), anti-Markovnikov bromide (HBr/ROOR), vicinal dihalide (X2), halohydrin (X2/H2O), epoxide (mCPBA), syn-diol (OsO4), saturated alkane (H2/Pd), and carbonyl cleavage products (O3). Stereochemistry (syn or anti) is noted next to each transformation. The diagram serves as a visual reference for all alkene reactions covered in lectures 13-14.</image>
