-1-
REARRANGEMENTS NOTES
Mechanistic Aspects of Rearrangements
Nature of the Rearrangement
It can vary from being truly stepwise to migration occurring in concert with initial
ionisation. These two situations can be considered as intramolecular analogues of
SN1 and SN2 respectively. Hence, it has profound stereochemical implications at both
the migration origin and the terminus if the centres are chiral. With non-racemic
substrates, the generation of a free carbocation at either the migration terminus or
origin will result in loss of stereochemical integrity at that centre, whereas a
concerted migration with no intermediate will result in inversion of the absolute
stereochemistry at the terminus.
Migratory Aptitude
This is the ease with which any particular group will undergo nucleophilic 1,2-shifts. It
is related to electron donating capacity, but such values are not quantifiable as a
single group will show different aptitudes for different reactions/conditions.
Note that in some instances, for example the Beckmann Rearrangement, only one
group ever migrates regardless of the aptitude, simply because of stereoelectronic
requirements for the reaction. Likewise, in for example the pinacol rearrangement,
the most stable cation controls the reaction pathway, as opposed to the migrating
group.
A wide range of other factors, such as steric and conformational effects, play subtle
roles in determining whether a particular migration is favoured. Generally however,
aryl groups migrate more readily than alkyl groups, and within the aryl series, e-
donating substituents increase the propensity for migration. However, the position of
hydrogen within this framework is highly unpredictable.
Neighbouring Group Participation (Anchimeric Assistance)
This is where a substituent is capable of stabilising an adjacent carbocation by acting
as an intramolecular nucleophile. More details in the Stereoelectronics Notes.
Non-classical Carbonium Ions
While alkyl groups do not usually undergo σ-participation in acyclic or unstrained ring
systems, there is much evidence to suggest that this does occur in strained rings.
The species formed contain a two-electron, three-centre bond and are known as
“non-classical carbonium ions”. The most studied system in which σ-participation is
envisaged to occur is the 2-norbornyl system. It has been found that solvolysis of
optically pure norbornyl 2-exo-brosylate in acetic acid gave a racemic exo-acetate as
the sole product with no endo-material. Furthermore, it occurred 250 times faster.
These results were interpreted as implying that the reaction of the exo-substrate
occurred solely via a non-classical carbonium ion, whilst the endo substrate reacted
by initial formation of a classical carbenium ion which then rearranged to the non-
classical carbonium ion, but not before a small amount had reacted with solvent,
attack being sterically directed to the exo-face.
These Notes are copyright Alex Moss 2003. They may be reproduced without need for permission.
www.alchemyst.f2o.org
, -2-
Carbocation Induced Alkyl and Hydride Shifts
Wagner-Meerwein Shifts
These 1,2-alkyl shifts occur if it leads to the new carbocation being more stabilised
than the original. This is usually the case if the carbon adjacent to the positively
charged centre is secondary or tertiary. Subsequent elimination will then occur.
Saytzeff’s Rule is obeyed to give the most substituted alkene.
1,2-alkyl shifts have a rigorous stereochemical requirement for the bond at the
migration origin to lie very close to the axis of the vacant p-orbital of the carbocationic
centre. Whilst acyclic systems can usually adopt the correct conformation for this
alignment, this option may not be open to cyclic systems.
Pinacol Rearrangement
Treatment of 1,2 diols with acid, which converts them to carbonyls. The reaction can
also occur on β-aminoalcohols, halohydrins, epoxides and allylic alcohols.
It proceeds via a 1,2 alkyl shift, and the overall reaction is:
Control can be exerted by conditions, e.g.
Tiffeneau-Demjanov Reaction
Similar to the pinacol rearrangement, but via a β-amino alcohol derivative. This
specific reaction leads to one carbon ring expansion, and is very useful for
homologating cyclic ketones to give products containing 4-8 carbon atoms in the ring.
These Notes are copyright Alex Moss 2003. They may be reproduced without need for permission.
www.alchemyst.f2o.org
REARRANGEMENTS NOTES
Mechanistic Aspects of Rearrangements
Nature of the Rearrangement
It can vary from being truly stepwise to migration occurring in concert with initial
ionisation. These two situations can be considered as intramolecular analogues of
SN1 and SN2 respectively. Hence, it has profound stereochemical implications at both
the migration origin and the terminus if the centres are chiral. With non-racemic
substrates, the generation of a free carbocation at either the migration terminus or
origin will result in loss of stereochemical integrity at that centre, whereas a
concerted migration with no intermediate will result in inversion of the absolute
stereochemistry at the terminus.
Migratory Aptitude
This is the ease with which any particular group will undergo nucleophilic 1,2-shifts. It
is related to electron donating capacity, but such values are not quantifiable as a
single group will show different aptitudes for different reactions/conditions.
Note that in some instances, for example the Beckmann Rearrangement, only one
group ever migrates regardless of the aptitude, simply because of stereoelectronic
requirements for the reaction. Likewise, in for example the pinacol rearrangement,
the most stable cation controls the reaction pathway, as opposed to the migrating
group.
A wide range of other factors, such as steric and conformational effects, play subtle
roles in determining whether a particular migration is favoured. Generally however,
aryl groups migrate more readily than alkyl groups, and within the aryl series, e-
donating substituents increase the propensity for migration. However, the position of
hydrogen within this framework is highly unpredictable.
Neighbouring Group Participation (Anchimeric Assistance)
This is where a substituent is capable of stabilising an adjacent carbocation by acting
as an intramolecular nucleophile. More details in the Stereoelectronics Notes.
Non-classical Carbonium Ions
While alkyl groups do not usually undergo σ-participation in acyclic or unstrained ring
systems, there is much evidence to suggest that this does occur in strained rings.
The species formed contain a two-electron, three-centre bond and are known as
“non-classical carbonium ions”. The most studied system in which σ-participation is
envisaged to occur is the 2-norbornyl system. It has been found that solvolysis of
optically pure norbornyl 2-exo-brosylate in acetic acid gave a racemic exo-acetate as
the sole product with no endo-material. Furthermore, it occurred 250 times faster.
These results were interpreted as implying that the reaction of the exo-substrate
occurred solely via a non-classical carbonium ion, whilst the endo substrate reacted
by initial formation of a classical carbenium ion which then rearranged to the non-
classical carbonium ion, but not before a small amount had reacted with solvent,
attack being sterically directed to the exo-face.
These Notes are copyright Alex Moss 2003. They may be reproduced without need for permission.
www.alchemyst.f2o.org
, -2-
Carbocation Induced Alkyl and Hydride Shifts
Wagner-Meerwein Shifts
These 1,2-alkyl shifts occur if it leads to the new carbocation being more stabilised
than the original. This is usually the case if the carbon adjacent to the positively
charged centre is secondary or tertiary. Subsequent elimination will then occur.
Saytzeff’s Rule is obeyed to give the most substituted alkene.
1,2-alkyl shifts have a rigorous stereochemical requirement for the bond at the
migration origin to lie very close to the axis of the vacant p-orbital of the carbocationic
centre. Whilst acyclic systems can usually adopt the correct conformation for this
alignment, this option may not be open to cyclic systems.
Pinacol Rearrangement
Treatment of 1,2 diols with acid, which converts them to carbonyls. The reaction can
also occur on β-aminoalcohols, halohydrins, epoxides and allylic alcohols.
It proceeds via a 1,2 alkyl shift, and the overall reaction is:
Control can be exerted by conditions, e.g.
Tiffeneau-Demjanov Reaction
Similar to the pinacol rearrangement, but via a β-amino alcohol derivative. This
specific reaction leads to one carbon ring expansion, and is very useful for
homologating cyclic ketones to give products containing 4-8 carbon atoms in the ring.
These Notes are copyright Alex Moss 2003. They may be reproduced without need for permission.
www.alchemyst.f2o.org
