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Chapter 5. Stereochemistry
I)
Introductory Definitions
A) Constitutional Isomers - bonding sequence of the atoms is not the same.
B) Stereoisomers - same bonding sequence, but the orientation of the atoms in
space is different.
Cis-trans isomers are geometric isomers, but they are a special type of
stereoisomer.
C) Chiral - objects that have left- and right-handed forms. Chiral objects have a
mirror image that is different from the original object.
D) Achiral - means that the object and its mirror image are the same, i.e., they
are not chiral.
E) Enantiomers - stereoisomers whose mirror images are non-superimposable.
For most carbon compounds that are chiral, we have a carbon atom
attached to four different groups. Such a carbon atom is termed a chiral
carbon or an asymmetric carbon atom, or a stereocenter, or a chirality
center.
General Rules
1. A compound with no chiral carbon atom is usually achiral.
2. A compound with one chiral carbon is chiral.
3. A compound with more than one chiral atom may or may not be chiral.
An extension of our definition is to look for an internal mirror plane of
symmetry (  ). Chiral compounds do not have this mirror plane.
Example:
cis-1,2-dichlorocyclopentane does have an internal mirror
plane of symmetry; therefore, it is achiral.
trans-1,2-dichlorocyclopentane does not have an internal
mirror plane of symmetry; therfore, it is chiral.
Any molecule that has an internal mirror plane of symmetry( )
cannot be chiral, even though it may contain chiral carbon atoms.
If one cannot find an internal mirror plane of symmetry, that does not
necessarily mean that the molecule must be chiral.
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Conformers for straight-chains can also be chiral, but due to free rotation
about C-C bonds if there is no chiral carbon atom present, the molecule is
achiral.
Some exceptions to the above statement, or why we need the
internal plane of symmetry at times:
Allenes
Example:
2,3-pentadiene
CH3CH=C=CHCH3
This molecule has enantiomers but no carbon has four
different substituents. Verify this by building models.
II)
Absolute Configurations & R,S Nomenclature
A) Absolute Configuration - detailed stereochemical picture of a molecule that
includes how the atoms are arranged in space. This is the R,S system.
B) Relative Configuration - experimentally determined relationship between two
molecules even though we do not know the absolute configuration of either
one.
C) R,S - System or Cahn-Ingold-Prelog Convention
D) Rules:
1. Assign a "priority" to each group bonded to the chiral carbon
(1 = highest, 2, 3, 4 (lowest).
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a) The higher the atomic number, the higher the priority. (Note:
only concerned with atom bonded directly to chiral carbon).
b) For isotopes of the same element, the heavier isotopes have
higher priority.
2. In case of a tie, use the next atoms along the chain as a tiebreaker. Follow
path of highest priority. Also one high priority atom wins out over any
number of lower-priority atoms.
3. For double and triple bonds you break each pi-bond and add two
imaginary atoms, i.e.,
4. Put group 4 in the back of the molecule and trace an arrow from 1 to 2 to
3. If the arrow points clockwise then it is an R-enantiomer and if it is
counterclockwise it is the S-enantiomer.
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Practice Problems:
Identify Stereocenter as R or S.
CH3
CH3
F
H
H2N
NH2
F
R
A simple one to start with, notice that we go clockwise from group 1
(fluorine) to 2 (amino group) to 3 (methyl) so we know it is the R
stereoisomer.
CH2CH2Br
CH2CH2Br
CH(CH3)2
H3CH2C
H
(H3C)2HC
CH2CH3
R
This one requires a little more thought; looking for first point of
difference. Notice that the highest priority is not on the top even though it
contains a bromine. Remember you must start at the atom closest to the
chiral center and work outward. Here the priority goes clockwise from
group 1 (isopropyl) to 2 (ethyl bromide group) to 3 (ethyl) so we know it
is an R stereoisomer.
Stereochemistry must be shown to determine R or S configuration.
Work as many examples as you can; must become proficient at this!
E) Molecules with more than one chiral carbon
Fisher projections are used to compare these stereoisomers.
Rules:
1. Vertical lines point away from us and horizontal lines point toward us.
2. Carbon chain is drawn along the line of the Fisher projection, usually
placing the most oxidized carbon substituent at the top.
3. Interchanging groups on the horizontal part of the cross converts one
stereoisomer into its mirror image.
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4. To compare mirror images the Fisher projections can
a) only be rotated 180 degrees
b) they can not be flipped over
If more than one chiral carbon then it is possible to have diastereomers
which are stereoisomers that are not mirror images and meso compounds
whose mirror image is the same or it has an internal plane of symmetry.
2n Rule:
If we have n chiral carbon atoms then the maximum
number of stereoisomers is given by 2n.
Example:
CHOCH(OH)CH(OH)CH2OH
chiral carbons in bold.
2 chiral carbons means there are 4 stereoisomers possible.
2 Sets of Enantiomers & 2 Sets of Diastereomers
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Example:
CH3CH(OH)CH(OH)CH3
Note: Only 3 stereoisomers in this case, not four as predicted.
Example:
CH3CH(OH)CH(OH)CH(OH)CH(OH)CH2CH3
How many possible stereoisomers exist?
Draw the Fisher projections for all possible enantiomers.
F) Assigning R & S using Fisher projections
Rule: Interchange groups two at a time leaving the backbone chain constant.
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G) Properties of Stereoisomers
1. Diastereomers have different physical properties and hence can be
separated.
2. Enantiomers have identical physical properties (except for the rotation of
plane polarized light) and can not be separated. It is possible to separate
out enantiomers, more on this later.
III)
Optical Activity
A) Plane polarized light: composed of waves that vibrate in only one plane.
1. Rotation of this plane-polarized light is done using a polarimeter.
2. Optical activity - observed when plane-polarized light is rotated by
substances that are known as optically active.
Enantiomers are also called optical isomers and they rotate the
plane of polarized light by exactly the same amount but in opposite
directions.
Dextrorotatory = clockwise rotation (+)
Levorotatory = counterclockwise rotation (-)
No relationship to R & S configurations !
3. Specific Rotation
[]
[  ] =  (observed) / c l
 (observed) = rotation observed in the polarimeter.
c= concentration in g / mL
L = sample cell path length (dm)
Usually measured at 25 C using the D line of the sodium spectrum.
B) Racemic Mixture (Racemate)
1. A racemic mixture, also called a racemate or () pair or (d,l) pair, is a
50:50 mixture of a pair of enantiomers and it appears to be optically
inactive.
2. Note: A reaction that uses optically inactive reactants and catalysts cannot
produce a product that is optically active. Any chiral product must be
formed as a racemic mixture.
3. Optical purity (o.p.) = the ratio of the mixture's rotation to the rotation of
the pure enantiomer x 100%
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o.p. = (observed rotation / rotation of pure enantiomer) x 100%
4. Enantiomeric excess (e.e.) = method for expressing the relative amounts of
enantiomers in a mixture and yields the same results as optical purity.
e.e. = [ | d-l | / d + l ] x 100%
C) To separate enantiomers we first need to convert them into diastereomers
using an optically active chiral molecule or system.
D) Reaction mechanisms are often delineated by using chiral molecules. We will
see the following during our journey:
1. Reactions at a chiral carbon atom can result in
a) Inversion of configuration of the product
b) Racemization of the product
c) Retention of configuration of the product
2. Reactions at achiral carbon atoms
a) Can not tell things such as inversion of configuration
3. Generation of new chiral carbon atom
a) Most of the time we get a racemic product unless an enzyme of chiral
reagent (catalyst) is involved. Such a reaction is called asymmetric
induction.
b) A chiral carbon can cause a specific reaction to happen at another
center.
Chapter 5
Questions for Problem Set Notebook
Assignment 10
5-27, 5-29, 5-31 through 5-37