Difficulty: Intermediate to Advanced | Prerequisites: Part 1 of these notes (halogenation, halohydrin, hydrogenation), epoxide chemistry basics
This set of reactions completes the core alkene addition toolkit. Where Part 1 covered halogen and hydrogen additions, these four reactions focus on oxygen-containing products: diols (from dihydroxylation), carbonyl compounds (from ozonolysis), and alcohols (from hydroboration-oxidation). The syn vs. anti distinction you built in Part 1 returns here with dihydroxylation, and regioselectivity becomes important again with hydroboration-oxidation (anti-Markovnikov). Ozonolysis is different in kind: it cleaves the double bond entirely, which makes it a powerful tool for working backwards from products to identify an unknown alkene.
Syn-dihydroxylation (OsO4 or cold KMnO4) adds two OH groups to the same face. Anti-dihydroxylation (mCPBA then acid) adds two OH groups to opposite faces. Ozonolysis (O3, then DMS or Zn) cleaves the double bond completely into carbonyl fragments. Hydroboration-oxidation (BH3 then H2O2/NaOH) adds water across the double bond with anti-Markovnikov regiochemistry and syn stereochemistry.
Syn-dihydroxylation
The addition of two hydroxyl (OH) groups to the same face of a double bond. The reagent (OsO4 or cold KMnO4) delivers both oxygens in a single concerted step, so they must land on the same side. Think of it as stamping two OH groups onto the alkene from one direction.
Anti-dihydroxylation
The addition of two hydroxyl groups to opposite faces of a double bond. Achieved in two steps: first, an epoxide is formed (locking in the oxygen on one face), then acid-catalysed ring opening adds the second OH from the opposite face. Think of it as putting one OH on top, then flipping the molecule open to place the second OH on the bottom.
Osmate ester
The cyclic intermediate formed when OsO4 reacts with an alkene in a [3+2] cycloaddition. Both Os-O bonds form on the same face of the alkene, which is why the addition is syn. The ester is then hydrolysed to release the diol and regenerate the osmium reagent.
Ozonolysis
Cleavage of a carbon-carbon double bond using ozone (O3), followed by a reductive workup (DMS or Zn). The double bond is completely broken, and each carbon of the former double bond becomes a carbonyl (C=O). Think of it as scissors that cut the molecule at the double bond.
Reductive workup (DMS or Zn)
The second step in ozonolysis that reduces the ozonide intermediate to give aldehydes and/or ketones. Without a reductive workup (using H2O2 instead), you get carboxylic acids from aldehyde fragments.
Hydroboration-oxidation
A two-step sequence: first, BH3 (or BH3·THF) adds across the double bond in a syn, anti-Markovnikov fashion (boron goes to the less substituted carbon). Second, oxidation with H2O2/NaOH replaces the boron with OH. The net result is anti-Markovnikov addition of water with syn stereochemistry.
Anti-Markovnikov addition
The opposite of Markovnikov: the hydrogen (or, in hydroboration, the boron) adds to the more substituted carbon, and the OH ends up on the less substituted carbon. This is the defining feature that distinguishes hydroboration-oxidation from acid-catalysed hydration.
Concerted mechanism
A mechanism in which bond-making and bond-breaking happen simultaneously in a single step, with no intermediate. Both syn-dihydroxylation (the [3+2] cycloaddition) and hydroboration (the four-centred transition state) are concerted, which is why both give syn addition.
Reagents: OsO4, OH- (catalytic conditions) or cold, dilute KMnO4/OH-.
Product: A 1,2-diol (vicinal diol, also called a glycol) with both OH groups on the same face.
Mechanism:
OsO4 undergoes a concerted [3+2] cycloaddition with the alkene pi bond. Two Os-O bonds form simultaneously to both carbons, both from the same face. This produces a cyclic osmate ester.
The osmate ester is hydrolysed (with NaHSO3 or NMO as a reoxidant for catalytic conditions), releasing the syn-diol and regenerating OsO4.
Stereochemistry: Syn addition. The concerted [3+2] cycloaddition delivers both oxygens from the same face in a single step, so there is no opportunity for the groups to end up anti.
Key details:
OsO4 is toxic and expensive, so it is often used in catalytic amounts with a co-oxidant (NMO, N-methylmorpholine N-oxide) to regenerate it.
Cold, dilute KMnO4 with OH- gives the same syn-diol product, but KMnO4 can over-oxidise the diol and cleave the bond if conditions are not carefully controlled (warm or concentrated KMnO4 cleaves the alkene, similar to ozonolysis).
The wedge-dash notation in the product shows both OH groups on the same face (both wedge or both dash).
Reagents: Step 1: mCPBA (meta-chloroperoxybenzoic acid, written as RCO3H). Step 2: H3O+ (acid-catalysed hydrolysis).
Product: A 1,2-diol with the two OH groups on opposite faces (anti).
Mechanism:
mCPBA reacts with the alkene in a concerted "butterfly" mechanism, transferring an oxygen atom to form an epoxide. The oxygen is delivered to one face of the double bond.
The epoxide is opened by acid-catalysed hydrolysis (H3O+). Water attacks the more substituted carbon (or either carbon if symmetrical) from the back side (anti to the epoxide oxygen, via an SN2-like pathway). This places the second OH on the opposite face from the first.
Stereochemistry: Anti addition overall. Step 1 (epoxidation) is syn (oxygen goes to one face), but step 2 (ring opening) inverts at the attacked carbon, so the net result across both steps is anti.
Key details:
The anti-dihydroxylation is really two separate reactions chained together: epoxidation followed by hydrolysis.
Contrast this with syn-dihydroxylation: both deliver a diol, but with opposite stereochemistry. Exams frequently ask you to show how to make a syn-diol vs. an anti-diol from the same alkene.
In acid-catalysed opening of an unsymmetrical epoxide, nucleophilic attack occurs at the more substituted carbon (the carbon better able to stabilise partial positive charge in the transition state).
Reagents: Step 1: O3 (ozone). Step 2: DMS (dimethyl sulfide) or Zn (reductive workup).
Product: Aldehydes and/or ketones. Each carbon of the former double bond becomes a C=O.
A disubstituted carbon of the alkene becomes a ketone.
A monosubstituted carbon becomes an aldehyde.
A terminal =CH2 becomes formaldehyde (H2C=O).
Mechanism:
Ozone (O3) adds across the double bond in a [3+2] cycloaddition, forming a molozonide.
The molozonide rearranges to an ozonide.
The reductive workup (DMS or Zn) cleaves the ozonide, giving the carbonyl products.
Key details:
Ozonolysis is the only reaction in this set that breaks the C=C bond entirely. Every other reaction adds across the bond but leaves the carbon skeleton intact.
This reaction is especially useful in reverse: given the carbonyl products, you can deduce the structure of the starting alkene by mentally "gluing" the C=O carbons back together with a double bond.
If H2O2 is used in the workup instead of DMS, any aldehyde fragments are further oxidised to carboxylic acids. Ketones are unaffected.
Stereochemistry is not relevant to ozonolysis because the double bond is destroyed.
Reagents: Step 1: BH3·THF (borane-tetrahydrofuran complex). Step 2: H2O2, NaOH (alkaline hydrogen peroxide).
Product: An alcohol, with anti-Markovnikov regiochemistry. The OH ends up on the less substituted carbon.
Mechanism:
BH3 adds across the double bond in a single concerted step through a four-centred transition state. The boron (the electrophilic atom) attaches to the less substituted carbon, and a hydrogen from BH3 is delivered to the more substituted carbon. Both additions happen simultaneously from the same face of the double bond (syn addition). This step repeats up to three times, as BH3 has three B-H bonds available, producing a trialkylborane (R3B).
The oxidation step (H2O2/NaOH) replaces the boron with an OH group, retaining the configuration at carbon. The result is an alcohol on the less substituted carbon.
Regioselectivity: Anti-Markovnikov. Boron goes to the less substituted carbon because it is less sterically hindered. This means the final OH ends up on the less substituted carbon, the opposite of what Markovnikov's rule would predict for acid-catalysed hydration.
Stereochemistry: Syn addition. The concerted four-centred transition state delivers both the B and the H from the same face.
Key details:
Hydroboration-oxidation is the complement of acid-catalysed hydration: both add H and OH across the double bond, but hydroboration gives the anti-Markovnikov product and acid-catalysed hydration gives the Markovnikov product.
No carbocation is formed, so no rearrangements occur.
The boron is replaced by OH with retention of configuration (the stereochemistry at that carbon does not change during oxidation).
Reaction | Reagents | Product | Stereochemistry | Regiochemistry |
|---|---|---|---|---|
Syn-dihydroxylation | OsO4 / OH- (or cold KMnO4) | syn-1,2-diol | Syn | N/A |
Anti-dihydroxylation | 1) mCPBA 2) H3O+ | anti-1,2-diol | Anti | N/A |
Ozonolysis | 1) O3 2) DMS (or Zn) | Aldehydes / ketones | N/A (bond cleaved) | N/A |
Hydroboration-oxidation | 1) BH3·THF 2) H2O2 / NaOH | Alcohol | Syn | Anti-Markovnikov |
Syn-dihydroxylation is used in the Sharpless asymmetric dihydroxylation, one of the most important enantioselective reactions in pharmaceutical synthesis. K. Barry Sharpless received a share of the 2001 Nobel Prize in Chemistry for this work.
Ozonolysis is used in analytical chemistry and structure determination: by cleaving a complex alkene and identifying the carbonyl fragments, chemists can work backwards to determine where the double bond was in the original molecule.
Hydroboration-oxidation is widely used in organic synthesis to place an OH group on the less hindered carbon of a double bond, a transformation that acid-catalysed hydration cannot achieve.
Students often confuse syn-dihydroxylation and anti-dihydroxylation reagents. A reliable mnemonic: OsO4 = syn (Os, same side). mCPBA + acid = anti (two separate steps, two different faces).
Students forget that cold, dilute KMnO4 gives the same product as OsO4 (a syn-diol), but hot or concentrated KMnO4 cleaves the bond. Temperature and concentration matter.
Students sometimes think ozonolysis is reversible or partial. It is not: the double bond is completely destroyed. You get two separate carbonyl fragments.
Students mix up hydroboration-oxidation with acid-catalysed hydration. Both add H2O across the double bond, but they give opposite regiochemistry. Hydroboration = anti-Markovnikov (OH on less substituted carbon). Acid-catalysed hydration = Markovnikov (OH on more substituted carbon).
⚠️ "Show two different ways to make a 1,2-diol from this alkene" is a classic exam question. You need syn-dihydroxylation for one stereoisomer and anti-dihydroxylation for the other.
⚠️ Ozonolysis "reverse" problems are very common: you are given the carbonyl products and asked to reconstruct the starting alkene.
⚠️ Comparing hydroboration-oxidation vs. acid-catalysed hydration (Markovnikov vs. anti-Markovnikov) is a standard exam comparison.
⚠️ Be able to predict whether a concerted mechanism gives syn or anti addition. Both the OsO4 cycloaddition and the BH3 four-centred transition state are concerted and syn.
True or false: OsO4 gives anti-dihydroxylation.
False. OsO4 gives syn-dihydroxylation.
Ozonolysis of 2-butene (CH3CH=CHCH3) with DMS workup produces ______ .
Two equivalents of acetaldehyde (CH3CHO).
True or false: In hydroboration-oxidation, the OH ends up on the more substituted carbon.
False. The OH ends up on the less substituted carbon (anti-Markovnikov).
What reagent sequence gives an anti-1,2-diol from an alkene?
mCPBA, then 2) H3O+.
True or false: BH3 addition to an alkene proceeds through a carbocation intermediate.
False. It is a concerted, four-centred transition state with no intermediate.
Q: Show the reagents and products for both syn- and anti-dihydroxylation of (E)-2-butene. How do the products differ?
A: Syn-dihydroxylation (OsO4, OH-) gives the meso-2,3-butanediol (both OH groups on the same face). Anti-dihydroxylation (1. mCPBA, 2. H3O+) gives the (R,R) and (S,S) enantiomers of 2,3-butanediol (OH groups on opposite faces). The products are diastereomers of each other.
Q: An unknown alkene undergoes ozonolysis with DMS to give acetone (CH3COCH3) and formaldehyde (HCHO). What was the starting alkene?
A: Connect the two C=O carbons with a double bond: the alkene is 2-methylpropene (isobutylene), CH2=C(CH3)2.
Q: You want to convert 1-methylcyclohexene into trans-2-methylcyclohexanol. Which reaction do you use: acid-catalysed hydration or hydroboration-oxidation? Explain.
A: Neither reaction alone gives a trans alcohol directly from this substrate in one step. Hydroboration-oxidation gives syn, anti-Markovnikov addition (OH on the less substituted carbon, cis to the H). Acid-catalysed hydration gives Markovnikov addition (OH on the more substituted carbon). For a trans-diol specifically, you would need anti-dihydroxylation. The question tests your ability to distinguish regiochemistry from stereochemistry.
Q: What is the difference between using DMS and H2O2 as the workup reagent in ozonolysis?
A: DMS (or Zn) is a reductive workup and gives aldehydes from monosubstituted carbons. H2O2 is an oxidative workup and oxidises aldehyde fragments further to carboxylic acids. Ketone fragments are unaffected by either workup.
Q: Why does hydroboration give anti-Markovnikov regioselectivity?
A: Boron is the electrophilic atom and is also the larger atom in BH3. It preferentially bonds to the less sterically hindered (less substituted) carbon of the double bond. The hydrogen from BH3 is delivered to the more substituted carbon. Because the OH replaces the boron in the oxidation step, the OH ends up on the less substituted carbon.
These reactions connect back to Part 1 (halogenation, halohydrin, hydrogenation) through the syn/anti addition framework. Together, the seven reactions give you a complete toolkit for predicting addition products.
Anti-dihydroxylation connects directly to epoxide chemistry (Chapter on ethers and epoxides): the first step is epoxidation, and the second step is acid-catalysed ring opening, which you will see again in detail.
Ozonolysis connects to carbonyl chemistry (aldehydes and ketones chapter): the products are the starting materials for nucleophilic addition, reduction, and oxidation reactions you will study later.
Hydroboration-oxidation connects to alcohol chemistry and to the broader theme of Markovnikov vs. anti-Markovnikov selectivity, which recurs in radical additions and HBr/peroxide reactions.
syn-dihydroxylation, anti-dihydroxylation, OsO4, osmium tetroxide, KMnO4, potassium permanganate, mCPBA, meta-chloroperoxybenzoic acid, epoxidation, ozonolysis, ozone cleavage, reductive workup, DMS, dimethyl sulfide, hydroboration, BH3, borane, anti-Markovnikov, oxidation with H2O2 NaOH, 1,2-diol, vicinal diol, glycol, osmate ester, concerted mechanism, four-centred transition state, Sharpless dihydroxylation, alkene cleavage, carbonyl fragments, organic chemistry study notes