Molecular Rearrangements: Wagner–Meerwein, Pinacol and Neighbouring Group Participation

12.1Carbocations and 1,2-shifts

Most rearrangements in this unit are 1,2-shifts to an electron-deficient carbon: a group on the carbon next to a carbocation moves with its bonding pair to the cationic carbon. The cation is thereby moved one carbon over.

When does a shift happen?

• When the new cation is more stable: 2° → 3°, 1° → 2° or 3°, or a cation next to O or N (an oxocarbenium or iminium ion, the driving force of pinacol-type shifts).
• When ring strain is relieved: a cation next to a cyclobutane expands it to a cyclopentane (cyclobutylmethyl → cyclopentyl); this can happen repeatedly along a chain of spiro-cyclobutanes. Ring contraction occurs when it gives a tertiary cation or relieves crowding.
• The migrating bond must be roughly anti-periplanar (parallel) to the empty p orbital or to the departing group; in rigid rings this decides which bond moves.
• Shifts are fast, faster than capture by most nucleophiles, so any reaction that goes through a carbocation (SN1, E1, HX addition, acid hydration, Friedel–Crafts alkylation, acid dehydration) can give rearranged products.

Shifts in aromatic and alkylation chemistry

• n-Propyl chloride with AlCl₃ gives the isopropyl cation (1,2-H shift), so benzene gives cumene.
• A cation formed in a side chain can be captured by the aromatic ring of the same molecule (intramolecular Friedel–Crafts), usually closing a five- or six-membered ring (indanes, tetralins), often after a hydride or methyl shift to a tertiary cation.
• In strong acid (HCl/AlCl₃), alkyl groups on a benzene ring can move to the next carbon: ipso protonation gives an arenium ion, a 1,2-methyl shift moves the group, and loss of H⁺ restores the ring.

12.2Wagner–Meerwein rearrangements

The name is used for 1,2-alkyl (or aryl) shifts in carbocations, especially in bicyclic terpenes, where the shift changes the ring skeleton.

• α-Pinene + HCl: H⁺ adds to give the tertiary pinanyl cation. The strained four-membered ring opens by an alkyl shift that expands it, giving the bornyl (bicyclo[2.2.1]heptyl) cation. Cl⁻ adds from the less hindered exo face: bornyl chloride.
• Camphene hydrochloride ⇌ isobornyl chloride is the classic Wagner–Meerwein interconversion; it goes through the bridged 2-norbornyl cation.
• 2-Norbornyl cation: exo-2-norbornyl sulfonates solvolyse about 350 times faster than the endo isomers and give only exo products; an optically active exo substrate gives a racemic product. The C1–C6 bond participates (σ-participation) and forms a symmetrical, bridged (non-classical) ion.
• In bicyclic systems check Bredt’s rule: a C=C cannot form at a bridgehead of a small bicyclic ring, so H⁺ is lost from another position.

12.3Pinacol–pinacolone, semipinacol and migratory aptitude

Pinacol–pinacolone rearrangement

A 1,2-diol in acid loses water from one carbon to give a carbocation; a group on the neighbouring carbinol carbon migrates to it; the cation left behind is stabilised by the OH oxygen (an oxocarbenium ion, i.e. a protonated ketone), which loses H⁺.

• Which OH leaves? The one that gives the more stable cation (diaryl > aryl/alkyl > tertiary alkyl > secondary). A carbon bearing a strongly −I group (CF₃) ionises very slowly, so such a diol reacts slowly.
• Which group migrates? From the other carbon, by migratory aptitude. Aryl groups migrate through a bridged (phenonium-like) transition state, so electron-donating para groups help: p-anisyl (about 500) > p-tolyl (about 15) > phenyl (1) > p-chlorophenyl (about 0.7); ortho-substituted aryls migrate poorly (steric). Hydride usually migrates readily; among alkyl groups, tertiary > secondary ≈ ring CH₂ > ethyl > methyl, but the result depends on the cation formed and on which group is anti to the leaving water.
• Symmetrical diols (Ar₂C(OH)–C(OH)Ar′₂): either OH gives the same cation, so only migratory aptitude decides.
• Crossover test: heating two different diols together gives no mixed (crossover) products, so the migration is intramolecular.
• Cyclic diols: if a ring bond migrates, the ring expands (a cyclobutane diol gives a cyclopentanone) or contracts (1,2-dimethylcyclohexane-1,2-diol gives 1-acetyl-1-methylcyclopentane when a ring CH₂ migrates).

Semipinacol rearrangements

The same 1,2-shift towards a carbon next to an OH (or O⁻) group, but the cation (or leaving group) is produced in another way:

• from a 2-halo or 2-sulfonyloxy alcohol (base or Ag⁺);
• from an epoxide opened by a Lewis acid (BF₃): epoxide → aldehyde or ketone;
• from an alkene next to a carbinol carbon that is attacked by an electrophile (Br⁺ from NBS, H⁺): the new cation pulls a ring bond across, often expanding the ring, and the oxygen ends up as a C=O;
• from 2-amino alcohols with HNO₂ (Tiffeneau–Demjanov, ring expansion by one carbon).

A path that would need a primary carbocation (loss of water from a CH₂OH) is not followed; a secondary OH ionises instead, and hydride shifts lead to the oxygen-stabilised cation and finally an aldehyde.

Dienone–phenol rearrangement

A cyclohexadienone with two groups on the sp³ carbon (4,4-disubstituted) is protonated on oxygen; a group shifts from C4 to C3 and loss of H⁺ makes the ring aromatic: 4,4-dimethylcyclohexa-2,5-dienone gives 3,4-dimethylphenol. The group with higher migratory aptitude (aryl, a ring bond) moves.