Preparation of Alcohols from Alkenes
Alkenes serve as one of the most common starting materials for synthesizing alcohols. The method you choose determines two critical outcomes: where the OH group ends up (regiochemistry) and how it's oriented in 3D space (stereochemistry). This section reviews the major routes from alkenes to alcohols and 1,2-diols, then compares them so you can pick the right tool for a given synthesis problem.
Methods of Alcohol Preparation
Hydroboration-Oxidation
This is a two-step sequence that places the OH group on the less substituted carbon of the alkene (anti-Markovnikov).
- Treat the alkene with borane (), which undergoes syn addition across the double bond. The boron attaches to the less substituted carbon because steric effects favor that placement.
- Oxidize the resulting organoborane with hydrogen peroxide () in aqueous base (). This replaces the C–B bond with a C–OH bond, retaining the stereochemistry set in step 1.
Because the addition is syn, both the H and the OH end up on the same face of the double bond. This matters most with cyclic alkenes and internal alkenes where facial selectivity is visible. The method works well with terminal alkenes (e.g., 1-hexene → 1-hexanol), internal alkenes, and cyclic alkenes (e.g., cyclopentene → cis-2-cyclopentanol).
Oxymercuration-Demercuration
This two-step sequence places the OH group on the more substituted carbon (Markovnikov).
- Treat the alkene with mercury(II) acetate () in water. A mercurinium ion intermediate forms, a three-membered ring with mercury bridging the two alkene carbons. Water attacks the more substituted carbon of this intermediate (Markovnikov selectivity).
- Reduce the organomercury compound with sodium borohydride () to remove mercury and give the final alcohol.
The mercurinium ion intermediate prevents full carbocation rearrangement, but the reduction step destroys any stereochemical information. The result is typically a racemic mixture when a new stereocenter forms. For example, 1-butene gives 2-butanol as a racemic mixture, and 2-methyl-1-propene gives 2-methyl-2-propanol.
Quick rule of thumb: Need OH on the less substituted carbon? Use hydroboration-oxidation. Need OH on the more substituted carbon? Use oxymercuration-demercuration.
Synthesis of 1,2-Diols
Syn Dihydroxylation (Alkene Hydroxylation)
Osmium tetroxide () adds two OH groups to the same face of the double bond in a single concerted step, forming a cyclic osmate ester. A co-oxidant such as N-methylmorpholine N-oxide (NMO) regenerates so only catalytic amounts are needed.
Because the addition is syn, the geometry of the starting alkene directly controls the stereochemistry of the diol product:
- Cis alkene → erythro (meso) diol. For example, cis-2-butene gives (2R,3S)-butane-2,3-diol (a meso compound).
- Trans alkene → threo diol. For example, trans-2-butene gives a racemic mixture of (2R,3R)- and (2S,3S)-butane-2,3-diol.
There's no regioselectivity issue here since both carbons of the double bond receive an OH group.
Epoxide Hydrolysis (Anti Dihydroxylation)
Opening an epoxide with water gives a 1,2-diol with anti stereochemistry, the opposite facial relationship compared to dihydroxylation. The conditions matter:
- Basic conditions (/): The hydroxide ion acts as a nucleophile in an mechanism, attacking the less substituted (or less hindered) carbon with backside attack. This gives clean inversion at the carbon that's attacked. For example, (S,S)-cyclohexene oxide gives (R,R)-1,2-cyclohexanediol.
- Acidic conditions (): The protonated epoxide opens with more character, especially at more substituted positions. This can produce a mixture of stereoisomers because the nucleophile can attack from either face of a developing carbocation.
Syn vs. anti dihydroxylation: gives syn-1,2-diols. Epoxide hydrolysis gives anti-1,2-diols. Knowing which you need tells you which method to use.
Comparison of Alcohol Preparation Methods
Regioselectivity
| Method | Regiochemistry | Typical Product |
|---|---|---|
| Hydroboration-oxidation | Anti-Markovnikov | 1° or less substituted 2° alcohol (e.g., 1-butene → 1-butanol) |
| Oxymercuration-demercuration | Markovnikov | 2° or 3° alcohol (e.g., 1-butene → 2-butanol) |
| dihydroxylation | Both carbons hydroxylated | Vicinal diol (e.g., cis-2-butene → butane-2,3-diol) |
| Epoxide hydrolysis | Depends on conditions and substitution | Vicinal diol; favors less hindered carbon |
Stereochemistry
| Method | Addition Type | Stereochemical Outcome |
|---|---|---|
| Hydroboration-oxidation | Syn | Retains alkene geometry; single stereoisomer from a given face |
| Oxymercuration-demercuration | Not stereospecific | Racemic mixture (stereochemistry lost during reduction) |
| dihydroxylation | Syn | Cis alkene → erythro diol; trans alkene → threo diol |
| Epoxide hydrolysis (base) | Anti () | Inversion at attacked carbon; stereospecific |
| Epoxide hydrolysis (acid) | Anti ( character) | Mixture of stereoisomers possible |
Putting It All Together
When you're choosing a method for a synthesis problem, ask two questions in order:
- Where does the OH need to go? If on the less substituted carbon, hydroboration-oxidation. If on the more substituted carbon, oxymercuration-demercuration. If you need OHs on both carbons (a diol), use or epoxide hydrolysis.
- What stereochemistry do you need? Syn addition calls for hydroboration-oxidation (single OH) or (diol). Anti addition calls for epoxide hydrolysis. If stereochemistry doesn't matter, oxymercuration-demercuration is often the simplest choice since it avoids rearrangements and doesn't require careful stereochemical analysis.
Both hydroboration-oxidation and oxymercuration-demercuration are addition reactions across the double bond, but they differ in their intermediates. Hydroboration goes through a four-centered transition state (concerted, syn), while oxymercuration goes through a bridged mercurinium ion. These mechanistic differences are what produce the different regio- and stereochemical outcomes, so understanding the mechanism is the fastest way to predict the product.