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Migrations to Electron-Deficient Carbons
Wagner-Meerwein Rearrangements
1,2-Shifts of migrating groups to empty orbitals in carbocations or toward partially empty orbitals in developing
carbocations are the most common rearrangements of
organic molecules. Especially, migration of hydrogen atom
or alkyl or aryl groups in carbocations are called “WagnerMeerwein Rearrangements”
Migrations to Electron-Deficient Carbons
Wagner-Meerwein Rearrangements
“Wagner-Meerwein Rearrangements” do not involve the
bond breaking and formation because the following reaction
show the retention of configuration
Migrations to Electron-Deficient Carbons
Wagner-Meerwein Rearrangements
“Wagner-Meerwein Rearrangements” show that the
substituents invariably end up on the face of the ring from
which they started.
Migrations to Electron-Deficient Carbons
Wagner-Meerwein Rearrangements
“Wagner-Meerwein Rearrangements” are intramolecular
reactions which have TS resembling cyclic arrays of three
atomic orbitals called as “corner-protonated cyclopropanes”
Migrations to Electron-Deficient Carbons
Wagner-Meerwein Rearrangements
“Wagner-Meerwein Rearrangements” proceed most easily
when the carbocations are converted to more stable forms.
- Secondary cation to tertiary cation
- Simple cation to resonance-stabilized cation
Migrations to Electron-Deficient Carbons
Wagner-Meerwein Rearrangements
“Wagner-Meerwein Rearrangements” also proceed in the
cases of same stability of carbocations.
- Secondary cation to secondary cation
- Tertiary cation to tertiary cation
Migrations to Electron-Deficient Carbons
Wagner-Meerwein Rearrangements
“Wagner-Meerwein Rearrangements” must form the final
products that are thermodynamically more stable than the
starting materials. Some processes proceeding do appear
to require uphill steps (formation of less stable carbocation).
The Nature of The Migrating Groups
Migratory Aptitudes
(1) The relative yields of products from migrations of
different groups are not related to the abilities of the
groups to migrate
(2) Geometric factors can be important in migration.
A methyl group at the ring juncture of the two fused
carbocyclic rings will migrate in preference to the
migration of a primary or secondary alkyl group forming
part of one of the rings.
Migrations to Electron-Deficient Carbons
Migratory Aptitudes
(3) Methyl groups at axial positions of six-membered rings
are almost ideally positioned to migrate because the
bonds between the methyl groups and the rings are
nearly coplanar with the empty orbitals of the cations.
Equatorial substituents are unlikely to migrate.
(4) Steric factors may also significantly affect the open-chain
cations. Non-migrating substituents are forced into
“eclipsed position in the TS for rearrangement.
Migrations to Electron-Deficient Carbons
Migratory Tendencies
In some cases, migration tendencies can be determined by
comparing the rates of migration of different groups in
reactions with identical stationary groups.
Degenerate
Rearrangement –
The products have
the same structure
as the starting
material.
Ethyl group migrate
13~55 times as fast
as methyl group
Migrations to Electron-Deficient Carbons
Migratory Tendencies
It is possible to correct observed migratory aptitudes for
electronic and steric effects of stationary groups.
Example : pinacol rearrangement
methyl : ethyl : t-butyl = 1 : 17 : 4000
Migrations to Electron-Deficient Carbons
Migratory Tendencies
The general trend is that migration tendencies of alkyl
groups in carbocation rearrangements increase with
increasing substitution at the migrating carbon atoms.
Migrations to Electron-Deficient Carbons
Migratory Tendencies
Hydrogens usually migrate more rapidly than alkyl group
in Wagner-Meerwein rearrangements.
The hydrogen atom is only a slightly better migrator than
the methyl group and is probably a less effective migrator
than most larger alkyl groups.
Rearrangements of Carbocations
Competition with Other Reactions
The major products from many reactions in which carbocations are intermediates are usually formed without carbon
skeleton rearrangements. In these reactions, nucleophiles
react with carbocations more rapidly than rearrangements.
Rearrangements of Carbocations
Rearrangements Under Minimally Nucleophilic Conditions
If nucleophiles react exceptionally slowly with carbocations,
it is because the reaction mixtures contain strong Lewis
acids that complex with the nucleophiles and minimize
their reactivities. (Friedel-Crafts alkylation reaction)
Rearrangements of Carbocations
Rearrangements Under Minimally Nucleophilic Conditions
Carbocations can also have long lifetimes in superacids,
which are polar solvents with very low nucleophilicities.
- FSO3H, CF3SO3H
- BF3 in HF, AsF5 in FSO3H, SO2ClF in liquid SO2,
SbF5 in FSO3H (Magic acid)
Rearrangements of Carbocations
Rearrangements of Alkanes
Even alkanes having the lack of reactivity in ionic reactions
appear to rearrange rapidly in superacids or under FriedelCrafts conditions.
Pines and Wackher “Cationic chain mechanism for the
Isomerization of alkanes in the presence of Lewis acids
And promoters”
Rearrangements of Carbocations
Structures Favoring Carbocation Rearrangements
Several types of organic molecules in which carbocation
rearrangements are particularly likely to occur, even in
the presence of good nucleophiles
(1) The neopentyl system
2,2-Dimethylpropyl halides or sulfonates cannot undergo
E2 or SN2 reactions
Rearrangements of Carbocations
Structures Favoring Carbocation Rearrangements
(2) Relief of ring strain
Rearrangements are particularly likely to occur if they
result in a 3- or 4-membered ring expanding to form a
less strained structure.
Rearrangements of Carbocations
Structures Favoring Carbocation Rearrangements
(2) Relief of ring strain
Rearrangements of Carbocations
Structures Favoring Carbocation Rearrangements
(2) Relief of ring strain
In the very strained polycyclic system, relief of angle
strain is achieved by contraction of a cyclobutane ring.
Rearrangements of Carbocations
Structures Favoring Carbocation Rearrangements
(3) Pinacol and semipinacolic rearrangements
Tetramethylethylene glycol (pinacol) rearrange in acid
to form tert-butyl methyl ketone (pinacolone)
Formation of a new bond (p bond) provides the driving
force
Rearrangements of Carbocations
Structures Favoring Carbocation Rearrangements
(3) Pinacol and semipinacolic rearrangements
b-Halo alcohols and 1,2-epoxides are common starting
materials for semipinacolic rearrangements.
Rearrangements of Carbocations
Structures Favoring Carbocation Rearrangements
(3) Pinacol and semipinacolic rearrangements
b-Halo alcohols and 1,2-epoxides are common starting
materials for semipinacolic rearrangements.
Rearrangements of Carbocations
Structures Favoring Carbocation Rearrangements
(4) Rearrangements of a-hydroxyaldehydes and a-hydroxyketones (acyloin rearrangement)
In acid-catalyzed rearrangements of a-hydroxyaldehydes
or ketones, the migrating groups migrate to carbon atoms
of protonated carbonyl groups rather than to carbocation
centers.
Rearrangements of Carbocations
Structures Favoring Carbocation Rearrangements
(4) Rearrangements of a-hydroxyaldehydes and a-hydroxyketones (acyloin rearrangement)
Difference between acyloin and pinacolic rearrangements
- Competing elimination and substitution reactions of the
alcohol functions are unlikely to occur in acyloin one
- Pinacol rearrangements are usually highly exothermic,
but acyloin rearrangements are often similar in energy,
so that acyloin one are readily reversible
- Acyloin rearrangements can take place under basic as
well as acidic conditions
Rearrangements of Carbocations
Structures Favoring Carbocation Rearrangements
(4) Rearrangements of a-hydroxyaldehydes and a-hydroxyketones (acyloin rearrangement)
Acyloin rearrangements can take place under basic as
well as acidic conditions.
Rearrangements of Carbocations
Structures Favoring Carbocation Rearrangements
(4) Rearrangements of a-hydroxyaldehydes and a-hydroxyketones (acyloin rearrangement)
Many other aldehydes and ketones can undergo rearrangements in acid to form isomeric carbonyl compounds.
Rearrangements of Carbocations
Structures Favoring Carbocation Rearrangements
(5) The benzilic acid rearrangement
If diphenyl-1,2-dione (benzil) is heated in strong basic
solutions, it is quantitatively converted to salts of
benzilic acid
Rearrangements of Carbocations
Structures Favoring Carbocation Rearrangements
(5) The benzilic acid rearrangement
Rearrangements of Carbocations
Structures Favoring Carbocation Rearrangements
(5) The benzilic acid rearrangement
Rearrangements of Carbocations
Structures Favoring Carbocation Rearrangements
(6) Dienone-phenol rearrangements
Ortho-cyclohexadienones undergo acid-catalyzed rearrangements to yield phenols or esters of phenols
Rearrangements of Carbocations
Structures Favoring Carbocation Rearrangements
(6) Dienone-phenol rearrangements
Take place in solution of
sulfuric acid in acetic acid
or acetic anhydride
Rearrangements of Carbocations
Structures Favoring Carbocation Rearrangements
(6) Dienone-phenol rearrangements
1,3-Shifts of migrating cycloalkyl rings
Rearrangements of Carbocations
Structures Favoring Carbocation Rearrangements
(7) Allyl and benzyl group migrations in dienone-phenol
rearrangements
Acid-catalyzed migrations of benzyl groups in orthocyclohexadienones can proceed by [1,5] shifts as well as
[1,2] shifts
Rearrangements of Carbocations
Structures Favoring Carbocation Rearrangements
(7) Allyl and benzyl group migrations in dienone-phenol
rearrangements
Migrations of allyl groups in ortho- and para-cyclohexadienones can proceed by [3,3] shifts as well as [1,2] shifts
Rearrangements of Carbocations
Structures Favoring Carbocation Rearrangements
(8) Dienol-benzene rearrangements
Cyclohexadienols are very acid-sensitive compounds that
easily rearrange to form aromatic rings.
Rearrangements of Carbocations
Structures Favoring Carbocation Rearrangements
(8) Dienol-benzene rearrangements
In fused-ring systems, multiple migrations leading to
apparent [1,3] shifts are possible.
Long-Distance Migrations
Migrations in Open-chain Cations
While alkyl groups undergo only [1,2]-migration, there are
some reactions of open-chain carbocations that appear to
proceed by direct 1,5- or 1,6-migration of H or D atoms.
Long-Distance Migrations
Migrations in Open-chain Cations