352
NUCLEOPHILIC REACTIONS INVOLVING ENOLATE ANIONS
Although this section has been termed hydrogen
exchange, it is important to realize that we could also
visualize this simply as an enolate anion acting as
a base. This is also true of the next section, and in
some of the following sections we shall encounter
enolate anions acting as nucleophiles.
10.1.2 Racemization
The process of hydrogen exchange shown above
has implications if the α-carbon is chiral and
has a hydrogen attached. Removal of the proton
will generate a planar enol or enolate anion, and
regeneration of the keto form may then involve
supply of protons from either face of the double
bond, so changing a particular enantiomer into its
racemic form. Reacquiring a proton in the same
stereochemical manner that it was lost will generate
the original substrate, but if it is acquired from
the other face of the double bond it will give the
enantiomer, i.e. together making a racemate. Note
that removal and replacement of protons at the other
α-carbon, i.e. the methyl, will occur, but has no
stereochemical consequences.
O
CH 3
H 3 C
aq EtOH
NaOH or HCl
planar enolate anion
during reverse reaction, proton
can be added to either face
chiral centre must be
α to carbonyl and
contain an H substituent
CH 3
H
CH 3
O
HO
CH 3
H
CH 3
O
CH 3
H
CH 3
O
RS
S
racemic
product
H OH
CH 3
H
CH 3
O
RS
H 3 C
H 3 C
H 3 C
S
H 3 C
H 3 C
HO
CH 3
H 3 C
CH 3
H
CH 3
HO
H
H 3 C
S
H 3 C
CH 3
H
CH 3
OH
H 3 C
RS
+ H +
− H +
chiral
ketone
racemic
ketone
planar enol
in acid:
in base:
The chiral centre must be α to the carbonyl and
must contain a hydrogen substituent. If there is more
than one chiral centre in the molecule with only one
centre α to the carbonyl, then the other centres will
not be affected by enolization, so the product will
be a mixture of diastereoisomers of the original
compound rather than the racemate.
aq EtOH
NaOH or HCl
CH 3
H
Ph
O
S
Et
H CH 3
R
CH 3
H
Ph
O
S
Et
H CH 3
R
mixture of two diastereoisomers
CH 3
H
Ph
O
R
Et
H CH 3
R
+
chiral centre not α to
carbonyl and unaffected
NUCLEOPHILIC REACTIONS INVOLVING ENOLATE ANIONS
Although this section has been termed hydrogen
exchange, it is important to realize that we could also
visualize this simply as an enolate anion acting as
a base. This is also true of the next section, and in
some of the following sections we shall encounter
enolate anions acting as nucleophiles.
10.1.2 Racemization
The process of hydrogen exchange shown above
has implications if the α-carbon is chiral and
has a hydrogen attached. Removal of the proton
will generate a planar enol or enolate anion, and
regeneration of the keto form may then involve
supply of protons from either face of the double
bond, so changing a particular enantiomer into its
racemic form. Reacquiring a proton in the same
stereochemical manner that it was lost will generate
the original substrate, but if it is acquired from
the other face of the double bond it will give the
enantiomer, i.e. together making a racemate. Note
that removal and replacement of protons at the other
α-carbon, i.e. the methyl, will occur, but has no
stereochemical consequences.
O
CH 3
H 3 C
aq EtOH
NaOH or HCl
planar enolate anion
during reverse reaction, proton
can be added to either face
chiral centre must be
α to carbonyl and
contain an H substituent
CH 3
H
CH 3
O
HO
CH 3
H
CH 3
O
CH 3
H
CH 3
O
RS
S
racemic
product
H OH
CH 3
H
CH 3
O
RS
H 3 C
H 3 C
H 3 C
S
H 3 C
H 3 C
HO
CH 3
H 3 C
CH 3
H
CH 3
HO
H
H 3 C
S
H 3 C
CH 3
H
CH 3
OH
H 3 C
RS
+ H +
− H +
chiral
ketone
racemic
ketone
planar enol
in acid:
in base:
The chiral centre must be α to the carbonyl and
must contain a hydrogen substituent. If there is more
than one chiral centre in the molecule with only one
centre α to the carbonyl, then the other centres will
not be affected by enolization, so the product will
be a mixture of diastereoisomers of the original
compound rather than the racemate.
aq EtOH
NaOH or HCl
CH 3
H
Ph
O
S
Et
H CH 3
R
CH 3
H
Ph
O
S
Et
H CH 3
R
mixture of two diastereoisomers
CH 3
H
Ph
O
R
Et
H CH 3
R
+
chiral centre not α to
carbonyl and unaffected