CONFIGURATIONAL ISOMERS
117
Note that the ring systems with small bridges
illustrated here can have no conformational mobility,
and are quite fixed. Bornane also has no configurational
isomers. If we are going to bridge a cyclohexane ring
with a one-carbon bridge, there is only one way to
achieve this; in other words, the configuration at the
second bridgehead is fixed by that chosen at the first.
A similar situation confronted us with fused rings,
in that, in order to achieve the fusion of a small
ring, only a cis fusion was feasible (see Section 3.5.2).
Furthermore, bornane has a plane of symmetry and
can be superimposed on its mirror image, so only one
configurational isomer can exist.
bornane
≡
this type of bridging
is stereochemically
impossible
plane of
symmetry
≡
mirror image
We should compare this system with a 1,4disubstituted cyclohexane such as 4-methylcyclohexanecarboxylic acid (see Section 3.4.4). There is a
plane of symmetry in this molecule, so there are no
chiral centres; but geometric isomers exist, allowing
cis and trans stereoisomers. The restrictions imposed
by bridging have now destroyed any possibility of
geometric isomerism.
CO 2 H
H 3 C
CO 2 H
H 3 C
trans
cis
CO 2 H
CO 2 H
plane of
symmetry
plane of
symmetry
When we move on to camphor, a ketone derivative of bornane, we find this can exist in two enantiomeric forms because the plane of symmetry has been
destroyed. Nevertheless, there are only two configurational isomers despite the presence of two chiral centres;
bridging does not allow the other two variants to exist.
O
(−)-camphor
O
(+)-camphor
O
O
two chiral centres
only two stereoisomers
β-Pinene is representative of a bicyclo[3,1,1]heptane
system. This natural product has two chiral centres, but
can exist only in the (+)- and (−)-enantiomeric forms
shown.
(−)-β-pinene
(+)-β-pinene
two chiral centres
only two stereoisomers
Box 3.21
Stereochemistry of tropane alkaloids
The tropane alkaloids (−)-hyoscyamine and (−)-hyoscine are found in the toxic plants deadly nightshade (Atropa
belladonna) and thornapple (Datura stramonium) and are widely used in medicine. Hyoscyamine, usually in the
form of its racemate atropine, is used to dilate the pupil of the eye, and hyoscine is employed to control motion
sickness. Both alkaloids are esters of (−)-tropic acid.
The alcohol portion in hyoscyamine is tropine; in hyoscine it is the epoxide scopine. Tropine is an example
of an azabicyclo[3,2,1]octane system with a nitrogen bridge, whereas scopine is a tricylic system with a threemembered epoxide ring fused onto tropine. Note that systematic nomenclature considers an all-carbon ring system
with one carbon replaced by nitrogen; hence, tropane is an azabicyclooctane (see Section 1.4).
There are several interesting stereochemical features accommodated within these structures. First, both tropine
and scopine are optically inactive meso compounds; despite the chiral centres, two for tropine and four for
117
Note that the ring systems with small bridges
illustrated here can have no conformational mobility,
and are quite fixed. Bornane also has no configurational
isomers. If we are going to bridge a cyclohexane ring
with a one-carbon bridge, there is only one way to
achieve this; in other words, the configuration at the
second bridgehead is fixed by that chosen at the first.
A similar situation confronted us with fused rings,
in that, in order to achieve the fusion of a small
ring, only a cis fusion was feasible (see Section 3.5.2).
Furthermore, bornane has a plane of symmetry and
can be superimposed on its mirror image, so only one
configurational isomer can exist.
bornane
≡
this type of bridging
is stereochemically
impossible
plane of
symmetry
≡
mirror image
We should compare this system with a 1,4disubstituted cyclohexane such as 4-methylcyclohexanecarboxylic acid (see Section 3.4.4). There is a
plane of symmetry in this molecule, so there are no
chiral centres; but geometric isomers exist, allowing
cis and trans stereoisomers. The restrictions imposed
by bridging have now destroyed any possibility of
geometric isomerism.
CO 2 H
H 3 C
CO 2 H
H 3 C
trans
cis
CO 2 H
CO 2 H
plane of
symmetry
plane of
symmetry
When we move on to camphor, a ketone derivative of bornane, we find this can exist in two enantiomeric forms because the plane of symmetry has been
destroyed. Nevertheless, there are only two configurational isomers despite the presence of two chiral centres;
bridging does not allow the other two variants to exist.
O
(−)-camphor
O
(+)-camphor
O
O
two chiral centres
only two stereoisomers
β-Pinene is representative of a bicyclo[3,1,1]heptane
system. This natural product has two chiral centres, but
can exist only in the (+)- and (−)-enantiomeric forms
shown.
(−)-β-pinene
(+)-β-pinene
two chiral centres
only two stereoisomers
Box 3.21
Stereochemistry of tropane alkaloids
The tropane alkaloids (−)-hyoscyamine and (−)-hyoscine are found in the toxic plants deadly nightshade (Atropa
belladonna) and thornapple (Datura stramonium) and are widely used in medicine. Hyoscyamine, usually in the
form of its racemate atropine, is used to dilate the pupil of the eye, and hyoscine is employed to control motion
sickness. Both alkaloids are esters of (−)-tropic acid.
The alcohol portion in hyoscyamine is tropine; in hyoscine it is the epoxide scopine. Tropine is an example
of an azabicyclo[3,2,1]octane system with a nitrogen bridge, whereas scopine is a tricylic system with a threemembered epoxide ring fused onto tropine. Note that systematic nomenclature considers an all-carbon ring system
with one carbon replaced by nitrogen; hence, tropane is an azabicyclooctane (see Section 1.4).
There are several interesting stereochemical features accommodated within these structures. First, both tropine
and scopine are optically inactive meso compounds; despite the chiral centres, two for tropine and four for