Difficulty: Advanced | Prerequisites: Chapter 11 (alkene structure), Chapter 12 Part 1 (electrophilic addition basics, Markovnikov's rule, syn/anti addition, halonium ions).
This is the second half of Chapter 12 and covers the reactions that give you finer control over alkene chemistry: ways to hydrate without rearrangement (oxymercuration, hydroboration), ways to add oxygen across the double bond (epoxidation, dihydroxylation), ways to cleave the double bond entirely (ozonolysis), and a few special cases (cyclopropanation, radical bromination, polymerisation). These reactions round out your synthetic toolkit. If Part 1 gave you the basics, Part 2 gives you the precision tools.
Part 2 reactions let you add OH groups (Markovnikov or anti-Markovnikov, with or without rearrangement), build three-membered rings (cyclopropanes and epoxides), cleave double bonds to carbonyls (ozonolysis), add Br with anti-Markovnikov regiochemistry (radical bromination), and polymerise alkenes. Each reaction has a distinct mechanism, stereochemistry, and regiochemistry that you need to keep straight.
Oxymercuration-demercuration
A two-step sequence that hydrates an alkene with Markovnikov regiochemistry, anti addition, and no carbocation rearrangement. Step 1 uses Hg(OAc)₂ in water; step 2 uses NaBH₄ to remove the mercury. Think of it as the "clean" Markovnikov hydration.
Hydroboration-oxidation
A two-step sequence that hydrates an alkene with anti-Markovnikov regiochemistry and syn addition. Step 1: BH₃ or BH₃·THF adds across the double bond (B goes to the less substituted carbon). Step 2: NaOH/H₂O₂ replaces B with OH. No carbocation intermediate, no rearrangement.
Carbene
A neutral, divalent carbon species with only six electrons. Highly reactive. Can be singlet (paired electrons, sp2-like) or triplet (unpaired electrons, sp-like). Generated from diazo compounds (CH₂N₂) or by alpha-elimination of CHCl₃ with base.
Cyclopropanation
Addition of a carbene or carbenoid across a double bond to form a cyclopropane ring. Concerted syn addition. The geometry of the starting alkene is preserved in the product (cis alkene gives cis-substituted cyclopropane).
Carbenoid
A carbene-like species bonded to a metal (e.g. Simmons-Smith reagent, ICH₂ZnI). Behaves like a carbene but is more controllable.
Epoxidation
Conversion of an alkene to an epoxide (a three-membered ring containing oxygen) using a peracid. Concerted syn addition. The standard reagent is mCPBA (meta-chloroperoxybenzoic acid).
mCPBA (meta-chloroperoxybenzoic acid)
The most commonly used peracid for alkene epoxidation. The "extra" oxygen of the peracid is transferred to the alkene in a concerted, butterfly-like transition state.
Syn dihydroxylation
Addition of two OH groups to the same face of a double bond, giving a cis-1,2-diol. Reagents: OsO₄ (catalytic) with NMO (N-methylmorpholine N-oxide) as the reoxidant, or KMnO₄ under mild conditions.
Ozonolysis
Cleavage of both the sigma and pi bonds of a C=C double bond using ozone (O₃), followed by a workup step. Reductive workup (DMS or PPh₃) gives aldehydes and/or ketones. Oxidative workup (H₂O₂) gives carboxylic acids from aldehydes.
Radical bromination of alkenes
Addition of HBr to an alkene under radical conditions (peroxides, hv, or heat as initiators). Gives anti-Markovnikov addition of HBr. Only works with HBr, not HCl or HI. Radical chain mechanism.
Polymerisation
Repetitive addition of alkene monomers to form a long-chain polymer. Acid-catalysed (cationic) polymerisation proceeds through carbocation intermediates. The growing chain is a carbocation that attacks the next monomer.
Reagents: Step 1: Hg(OAc)₂, H₂O. Step 2: NaBH₄, NaOH/H₂O.
Two-step process that gives Markovnikov hydration
Key advantages over acid-catalysed hydration: no carbocation rearrangement, regioselective, stereoselective
Mechanism:
Step 1: Electrophilic mercury attacks the pi bond, forming a mercurinium ion (three-membered ring, similar to a halonium ion). Water opens the ring at the more substituted carbon (Markovnikov). Good leaving group (HgOAc) means no rearrangement.
Step 2: NaBH₄ replaces the mercury with hydrogen (demercuration). This step is not stereospecific.
Overall: anti addition, Markovnikov, no rearrangement
Regioselectivity follows from the same logic as halonium ions: the nucleophile attacks the more substituted carbon of the bridged intermediate
Reagents: Step 1: BH₃·THF (or BH₃·Et₂O). Step 2: NaOH, H₂O₂.
Two-step process that gives anti-Markovnikov hydration with syn addition
No carbocation intermediate, no rearrangement
Mechanism:
Step 1: BH₃ adds across the double bond in a concerted, four-centre transition state. Boron adds to the less substituted carbon (less sterically hindered), hydrogen to the more substituted. This is a syn addition.
The boron is both the electrophile and the delivery vehicle for H. The reaction repeats up to three times to use all three B-H bonds.
Step 2: Oxidation with NaOH/H₂O₂ replaces B with OH, retaining the stereochemistry.
Why anti-Markovnikov? Steric control. B is larger than H and goes to the less hindered carbon. There is also electronic alignment of C-H and B-H in the transition state.
The result is the OH on the less substituted carbon, which is the opposite of what acid-catalysed hydration or oxymercuration would give
Acid-catalysed hydration (H₃O⁺): Markovnikov, syn + anti, rearrangement possible
Oxymercuration-demercuration: Markovnikov, anti, no rearrangement
Hydroboration-oxidation: anti-Markovnikov, syn, no rearrangement
These three methods together let you place an OH group on either carbon of the double bond with control over regiochemistry and stereochemistry
Reagents: CH₂N₂ with hv or Cu catalyst (generates :CH₂ carbene), or Simmons-Smith reagent (CH₂I₂, Zn-Cu)
Product: cyclopropane ring fused to the former alkene carbons
Mechanism: concerted syn addition. The carbene or carbenoid inserts across both carbons simultaneously.
Stereochemistry of the alkene is preserved: a cis alkene gives a cis-substituted cyclopropane; a trans alkene gives a trans-substituted cyclopropane
Carbene types:
Singlet carbene: sp2-like, empty p orbital. Reacts as both electrophile and nucleophile simultaneously. Concerted syn addition.
Triplet carbene: sp-like, two unpaired electrons. Behaves like a diradical. Not stereospecific.
Dichlorocarbene (:CCl₂) from CHCl₃ + strong base (alpha-elimination): same concerted addition, gives a dichlorocyclopropane
Simmons-Smith carbenoid (ICH₂ZnI): behaves like :CH₂ but is bonded to zinc. Same syn addition.
Reagents: mCPBA (meta-chloroperoxybenzoic acid) in DCM. Alternative: CH₃CO₃H (peracetic acid)
Product: an epoxide (oxirane), a three-membered ring with one oxygen
Mechanism: concerted syn addition. The peracid delivers one oxygen atom to the same face of the alkene in a butterfly transition state.
Stereospecific: cis alkene gives a cis-epoxide; trans alkene gives a trans-epoxide
The alkene acts as the nucleophile; the peracid's electrophilic oxygen is the electrophile
Byproduct: the corresponding carboxylic acid (e.g. meta-chlorobenzoic acid from mCPBA)
Regioselectivity with unsymmetrical alkenes: the more electron-rich (more substituted) double bond reacts faster
Epoxide utility: epoxides are highly strained and easily opened by nucleophiles (covered in later chapters). This makes epoxidation a gateway to anti-dihydroxylation: mCPBA followed by acid-catalysed or base-catalysed ring opening gives a trans-1,2-diol.
Reagents: OsO₄ (catalytic) with NMO (N-methylmorpholine N-oxide) as reoxidant, plus H₂S workup. Or: OsO₄ (cat.) with H₂O₂ and NMO.
Alternative: KMnO₄ under cold, dilute conditions (also syn, but harsher)
Product: a cis-1,2-diol (both OH groups on the same face)
Mechanism: concerted syn addition of both oxygen atoms from OsO₄ across the double bond, forming an osmate ester intermediate. Reductive workup (H₂S) cleaves the Os-O bonds to release the diol.
OsO₄ is expensive and toxic; NMO acts as the "oxidant" that regenerates OsO₄ so only catalytic amounts are needed
The more electron-rich face of the alkene reacts first
Upjohn dihydroxylation: OsO₄ (cat.), NMO, H₂O (standard catalytic conditions)
Syn diol: OsO₄/NMO (syn dihydroxylation)
Anti diol: mCPBA epoxidation, then acid- or base-catalysed ring opening of the epoxide (anti addition of two OH groups)
These are complementary methods: choose the route based on whether you need cis or trans relative stereochemistry of the two OH groups
Reagents: Step 1: O₃ (ozone). Step 2: reductive workup (DMS, dimethyl sulfide, or PPh₃) or oxidative workup (H₂O₂).
Cleaves both the sigma and pi bonds of the C=C double bond
Concerted syn addition in step 1 to form a molozonide, which rearranges to an ozonide
Reductive workup (DMS): gives aldehydes and/or ketones
A monosubstituted alkene terminus gives an aldehyde (H-C=O)
A disubstituted alkene carbon gives a ketone (R₂C=O)
Oxidative workup (H₂O₂): aldehydes are further oxidised to carboxylic acids
Alternative conditions: Zn, CH₃S, or Cr₂O₃ for reductive workup
Ozonolysis is a powerful diagnostic tool: you can work backwards from the carbonyl products to deduce the structure of the original alkene
Reagents: HBr with peroxides (ROOR), hv, or heat as radical initiator
Only HBr works for this reaction; HCl and HI do not give anti-Markovnikov addition under radical conditions
Product: anti-Markovnikov addition of HBr (Br on the less substituted carbon)
Mechanism: radical chain
Initiation: peroxide homolyses to give radicals; radical abstracts H from HBr to generate Br·
Propagation A: Br· adds to the less substituted carbon of the alkene (forming the more stable carbon radical on the more substituted carbon)
Propagation B: the carbon radical abstracts H from another HBr, regenerating Br·
Termination: any two radicals combine
Regiochemistry is anti-Markovnikov because the Br radical adds to form the more stable (more substituted) carbon radical
No stereochemistry: the radical intermediate is planar (sp2), so attack occurs from both faces. No stereospecificity.
Acid-catalysed (cationic) polymerisation: H₂SO₄ or similar acid protonates the alkene to form a carbocation, which then attacks the next alkene monomer, extending the chain
Mechanism is a repeated electrophilic addition: each new C-C bond forms by carbocation attack on the pi bond of the next monomer
The chain grows until terminated
This is the basis for industrial production of many common plastics
Reaction | Reagents | Regiochemistry | Stereochemistry | Rearrangement? | Key Feature |
|---|---|---|---|---|---|
Oxymercuration-demercuration | 1. Hg(OAc)₂, H₂O 2. NaBH₄ | Markovnikov | Anti | No | Clean Markovnikov hydration |
Hydroboration-oxidation | 1. BH₃·THF 2. NaOH, H₂O₂ | Anti-Markovnikov | Syn | No | OH on less substituted C |
Cyclopropanation | CH₂N₂/hv or CH₂I₂/Zn-Cu | N/A | Syn (concerted) | No | Preserves alkene geometry |
Epoxidation | mCPBA, DCM | More sub. C=C reacts faster | Syn (concerted) | No | Gateway to anti-diols |
Syn dihydroxylation | OsO₄ (cat.), NMO | More e-rich face | Syn | No | Cis-1,2-diol |
Ozonolysis | 1. O₃ 2. DMS or H₂O₂ | N/A (cleavage) | N/A | No | Cleaves C=C entirely |
Radical HBr | HBr, ROOR/hv | Anti-Markovnikov | None (racemic) | No | Only works with HBr |
Polymerisation | H₂SO₄ (cationic) | Markovnikov (chain growth) | N/A | Possible | Repeated addition |
Epoxidation is central to pharmaceutical manufacturing. Many drug molecules contain epoxide intermediates or are built through stereoselective epoxidation steps. Ozonolysis is used both industrially (to produce azelaic acid from oleic acid for skincare and polymer applications) and in the lab as a diagnostic tool to determine alkene structure. The Sharpless asymmetric dihydroxylation (a refinement of OsO₄ dihydroxylation with chiral ligands) won the 2001 Nobel Prize in Chemistry.
Students often think hydroboration gives Markovnikov products. It does not. Boron goes to the less substituted carbon (anti-Markovnikov), and oxidation replaces B with OH in the same position.
Students forget that radical anti-Markovnikov addition only works with HBr. HCl and HI do not undergo this reaction because the thermodynamics of the propagation steps are unfavourable for those reagents.
Students confuse syn dihydroxylation (OsO₄, gives cis-diol) with epoxidation followed by ring opening (gives trans-diol). These are complementary, not interchangeable.
Students assume ozonolysis always gives aldehydes. It gives ketones from internal (disubstituted) alkene carbons and aldehydes from terminal (monosubstituted) carbons. Oxidative workup further converts aldehydes to carboxylic acids.
⚠️ The three hydration methods (acid-catalysed, oxymercuration, hydroboration) are a classic exam comparison. Know the regiochemistry, stereochemistry, and rearrangement risk for each.
⚠️ Ozonolysis product prediction is a standard exam question. Given an alkene, draw the carbonyl fragments. Given the fragments, deduce the original alkene.
⚠️ Epoxidation stereochemistry: know that mCPBA gives syn addition, and that a subsequent ring opening can give either syn or anti diol depending on conditions.
⚠️ Radical HBr is the only anti-Markovnikov H-X addition. If an exam question says "HBr, peroxides," the answer is anti-Markovnikov. Without peroxides, it is Markovnikov.
⚠️ Cyclopropanation preserves alkene geometry. Cis in, cis out. Trans in, trans out. This is a quick test of whether you understand concerted syn addition.
True or false: Oxymercuration-demercuration gives anti-Markovnikov hydration. (False. It gives Markovnikov hydration, with no rearrangement.)
Fill in the blank: In hydroboration, the boron adds to the ______ substituted carbon. (Less)
True or false: Radical addition of HCl to an alkene gives anti-Markovnikov products. (False. Only HBr undergoes radical anti-Markovnikov addition.)
Fill in the blank: Ozonolysis with reductive workup (DMS) converts alkenes into ______ and/or ______. (Aldehydes and/or ketones)
True or false: mCPBA epoxidation is an anti addition. (False. It is a concerted syn addition.)
Q: You need to convert 1-methylcyclohexene into 2-methylcyclohexanol with the OH on the less substituted carbon. Which reagent set do you choose?
A: Hydroboration-oxidation (1. BH₃·THF, 2. NaOH/H₂O₂). This gives anti-Markovnikov, syn addition, placing the OH on the less substituted carbon.
Q: What products form when 2-methyl-2-butene undergoes ozonolysis with reductive workup (DMS)?
A: Acetone (CH₃COCH₃) and acetaldehyde (CH₃CHO). The double bond is cleaved, and each fragment becomes a carbonyl. The disubstituted end gives a ketone; the monosubstituted end gives an aldehyde.
Q: Explain why treating an alkene with HBr in the presence of peroxides gives a different product than HBr alone.
A: Peroxides generate radicals that initiate a radical chain mechanism. In the radical pathway, Br· adds to the less substituted carbon (forming the more stable radical on the more substituted carbon), giving anti-Markovnikov addition. Without peroxides, the reaction follows the ionic (Markovnikov) pathway through a carbocation.
Q: How would you convert cis-2-butene into a cis-1,2-diol? Into a trans-1,2-diol?
A: Cis-diol: OsO₄ (cat.) with NMO (syn dihydroxylation delivers both OH groups to the same face). Trans-diol: mCPBA epoxidation (syn, gives the cis-epoxide), then acid- or base-catalysed ring opening (anti, inverts one centre), giving the trans-diol overall.
Q: A singlet carbene reacts with trans-2-butene. What is the stereochemistry of the cyclopropane product?
A: Trans-disubstituted cyclopropane. Singlet carbene addition is concerted and syn, so the geometry of the alkene is preserved in the product.
Epoxide chemistry connects forward to nucleophilic ring-opening reactions (SN2 at the less hindered carbon, or acid-catalysed opening at the more substituted carbon). Ozonolysis is a bridge to carbonyl chemistry (aldehydes and ketones), which dominates the second half of most organic chemistry courses. Radical bromination links back to radical halogenation of alkanes (Chapter 5) and forward to radical polymerisation. The syn dihydroxylation concept reappears in asymmetric synthesis when chiral ligands are used with OsO₄ (Sharpless AD).
Oxymercuration, demercuration, mercurinium ion, Hg(OAc)₂, NaBH₄, hydroboration, oxidation, BH₃, THF, anti-Markovnikov hydration, syn addition, carbene, singlet carbene, triplet carbene, carbenoid, Simmons-Smith, cyclopropanation, CH₂N₂, diazomethane, epoxidation, mCPBA, peracid, epoxide, oxirane, butterfly transition state, syn dihydroxylation, OsO₄, osmium tetroxide, NMO, N-methylmorpholine N-oxide, Upjohn dihydroxylation, cis-diol, trans-diol, ozonolysis, ozone, ozonide, molozonide, DMS, dimethyl sulfide, reductive workup, oxidative workup, radical bromination, HBr peroxides, anti-Markovnikov HBr, radical chain, initiation, propagation, termination, polymerisation, cationic polymerisation, dimerisation, oligomerisation