Stereochemistry

&
Chiral Molecules
 Stereochemistry
• stereochemistry is the three-dimensional structure of a
molecule.
• As a consequence of stereochemistry, apparently minor
differences in 3-D structure can result in vastly different
properties. We can observe this by considering starch and
cellulose, which are both composed of the same repeating
unit.
Stereochemistry of Carbohydrates
 Two Major Classes of Isomers

• isomers are different compounds with the same

molecular formula.
• The two major classes of isomers are constitutional
isomers and stereoisomers.

• Constitutional isomers have different IUPAC names,

the same or different functional groups, different
physical properties and different chemical properties.

• Stereoisomers differ only in the way the atoms are

oriented in space. They have identical IUPAC names
(except for a prefix like cis or trans and E or Z). They
always have the same functional group.
 Configurational Isomers

• Configurational isomers have a particular three-

dimensional arrangement of atoms called a
configuration.
• Configuration is the spatial array of atoms that
distinguishes stereoisomers.

• Configurational isomers are stereoisomers that

differ in configuration.
Constitutional Isomers vs Stereoisomers
Chirality or Handedness

• Although everything has a mirror image, mirror images

may or may not be superimposable.
• Some molecules are like hands. Left and right hands are
mirror images, but they are not identical, or
superimposable.
Achiral Objects and Molecules

• Other molecules are like

socks. Two socks from a pair
are mirror images that are
superimposable. A sock and
its mirror image are identical.
• A molecule or object that is
superimposable on its mirror
image is said to be achiral.
 Achiral Molecules
• Do these molecules conatain a Plane of Symmetry (Mirror Plane)?
 Chiral Molecules
• The molecule labeled A and its mirror image labeled B
are not superimposable. No matter how you rotate A and
B, all the atoms never align. Thus, CHBrClF is a chiral
molecule, and A and B are different compounds.
• A and B are stereoisomers—specifically, they are
enantiomers.
• A carbon atom with four different groups is a tetrahedral
stereogenic center.
 Chiral vs Achiral
• In general, a molecule with no stereogenic centers will
not be chiral. There are exceptions to this that will be
considered in Chapter 17.
• With one stereogenic center, a molecule will always be
chiral.
• With two or more stereogenic centers, a molecule may
or may not be chiral, e.g. Meso compound (contains a
plane of symmetry or a mirror plane)
• Achiral molecules contain a plane of symmetry but chiral
molecules do not.
• A plane of symmetry is a mirror plane that cuts the
molecule in half, so that one half of the molecule is a
reflection of the other half.
Plane of Symmetry
or
Mirror Plane
Chiral vs Achiral
 Stereogenic Centers
• To locate a stereogenic center, examine the four groups
—not the four atoms—bonded to each tetrahedral
carbon atom in a molecule.
• Omit from consideration all C atoms that cannot be
tetrahedral stereogenic centers. These include
• Methylene and methyl units, i. e. CH2 and CH3 groups
respectively.
• Any sp or sp2 hybridized Carbons, e.g. triple bonds,
and double bonds in alkenes (C=C) and carbonyls
(C=O).
 Number of Stereogenic Centers in a Molecule
• Larger organic molecules can have two, three or even
hundreds of stereogenic centers.
Enantiomers
 Enantiomers

One of a pair of molecular species that

are mirror images of each other and
not superposable.
They are mirror-image stereoisomers.
 Drawing Enantiomers

• To draw both enantiomers of a chiral compound such as

2-butanol, use the typical convention for depicting a
tetrahedron: place two bonds in the plane, one in front of
the plane on a wedge, and one behind the plane on a
dash. Then, to form the first enantiomer, arbitrarily place
the four groups—H, OH, CH3 and CH2CH3—on any bond
to the stereogenic center. Then draw the mirror image.
Pairs of Enantiomers
Stereogenic Centers in a cyclic Alkane
• Stereogenic centers may also occur at carbon atoms
that are part of a ring.
• To find stereogenic centers on ring carbons, always
draw the rings as flat polygons, and look for tetrahedral
carbons that are bonded to four different groups.
Enantiomers of 3-methylcyclohexene

• In 3-methylcyclohexene, the CH3 and H substituents that

are above and below the plane of the ring are drawn with
wedges and dashes as usual.
 Enantiomers of Biomolecules

• Many
biologically
active
molecules
contain
stereogenic
centers on
ring carbons.
 Polycyclic Ethers
• How many stereogenic centers are in this
polycyclic ether structure?

O
H
O H
H
H
O
H H
O
Me
H O
H
HO
H OH O
H
R/S Isomers
Labeling Stereogenic Centers with R or S
• Since enantiomers are two different compounds, they
need to be distinguished by name. This is done by
adding the prefix R or S to the IUPAC name of the
enantiomer.
• Naming enantiomers with the prefixes R or S is called
the Cahn-Ingold-Prelog system.
• To designate enantiomers as R or S, priorities must be
assigned to each group bonded to the stereogenic
center, in order of decreasing atomic number. The atom
of highest atomic number gets the highest priority (1).
Priority Rules for Naming Enantiomers (R or S)

• If two atoms on a stereogenic center are the same,

assign priority based on the atomic number of the atoms
bonded to these atoms. One atom of higher priority
determines the higher priority.
 Priority of Isotopes on a Stereogenic Center

• If two isotopes are bonded to the stereogenic center,

assign priorities in order of decreasing mass number.
Thus, in comparing the three isotopes of hydrogen, the
order of priorities is:
Priority Rules for Multiple Bonds in (R or S) Labeling
• To assign a priority to an atom that is part of a multiple bond,
treat a multiply bonded atom as an equivalent number of
singly bonded atoms. For example, the C of a C=O is
considered to be bonded to two O atoms.

• Other common multiple bonds are drawn below:

Examples Assigning Priorities
Cahn-Ingold-Prelog System for
Naming Enantiomers R or S
R or S Enantiomers
Positioning the Molecule for R/S Assignment
R-enantiomer (Clockwise Rotation)
S-enantiomer (Counterclockwise Rotation)
Manipulation of Chiral Molecules
Switching any two groups on a molecule with a
single stereogenic center, converts the
molecule into its enantiomer.
 Physical Properties of Stereoisomers
• Enantiomers have identical physical properties, except
for how they interact with plane-polarized light.
• Plane-polarized (polarized) light is light that has an
electric vector that oscillates in a single plane. Plane-
polarized light arises from passing ordinary light
through a polarizer.
• A polarimeter is an instrument that allows polarized light
to travel through a sample tube containing an organic
compound. It permits the measurement of the degree to
which an organic compound rotates plane-polarized
light.
 Polarimeter
• With achiral compounds, the light that exits the sample
tube remains unchanged. A compound that does not
change the plane of polarized light is said to be optically
inactive.
 Optically Active Compounds
• With chiral compounds, the plane of the polarized light is
rotated through an angle . The angle  is measured in
degrees (0), and is called the observed rotation. A
compound that rotates polarized light is said to be optically
active.
 Rotation of Polarized Light
• The rotation of polarized light can be clockwise or
anticlockwise.
• If the rotation is clockwise (to the right of the noon
position), the compound is called dextrorotatory. The
rotation is labeled d or (+).
• If the rotation is counterclockwise, (to the left of noon),
the compound is called levorotatory. The rotation is
labeled l or (-).
• Two enantiomers rotate plane-polarized light to an equal
extent but in opposite directions. Thus, if enantiomer A
rotates polarized light +50, the same concentration of
enantiomer B rotates it –50.
• No relationship exists between R and S prefixes and the
(+) and (-) designations that indicate optical rotation.
 Racemates
• An equal amount of two enantiomers is called a
racemate or a racemic mixture. A racemic mixture is
optically inactive. Because two enantiomers rotate
plane-polarized light to an equal extent but in opposite
directions, the rotations cancel, and no rotation is
observed.
 Specific Rotation
• Specific rotation is a standardized physical constant for
the amount that a chiral compound rotates plane-
polarized light. Specific rotation is denoted by the
symbol [] and defined using a specific sample tube
length (l, in dm), concentration (c in g/mL), temperature
(25 0C) and wavelength (589 nm).
 Optical Purity
• Enantiomeric excess (optical purity) is a measurement of
how much one enantiomer is present in excess of the
racemic mixture. It is denoted by the symbol ee.
ee = % of one enantiomer - % of the other enantiomer.

• Calculating ee - If a mixture contains 75% of one

enantiomer and 25% of the other, the enantiomeric
excess is 75% - 25% = 50% ee.
• 50% ee means that there is a 50% excess of one
enantiomer over the racemic mixture.
• The enantiomeric excess can also be calculated if the
specific rotation [] of a mixture and the specific rotation
[] of a pure enantiomer are known.
ee = ([] mixture/[] pure enantiomer) x 100.
Diastereomers
Relative Configuration
 Chiral Molecules with more than one
Stereocenter
• For a molecule with n stereogenic centers, the maximum
number of stereoisomers is 2n. Let us consider the stepwise
procedure for finding all the possible stereoisomers of 2,3-
dibromopentane.
 Diastereomers & Enantiomers
2,3-dibromopentane
 Enantiomers of 2,3-dibromobutane
• Let us now consider the stereoisomers of 2,3-dibromobutane.
Since this molecule has two stereogenic centers, the maximum
number of stereoisomers is 4.

• To find all the stereoisomers of 2,3-dibromobutane, arbitrarily

add the H, Br, and CH3 groups to the stereogenic centers,
forming one stereoisomer A, and then draw its mirror image, B.
 Meso Compounds

• To find the other two stereoisomers if they exist, switch the

position of two groups on one stereogenic center of one
enantiomer only. In this case, switching the positions of H and
Br on one stereogenic center of A forms C, which is different
from both A and B.
 Meso Compounds
• A meso compound is an achiral compound that contains
tetrahedral stereogenic centers. All meso compounds
contain a plane of symmetry.
• Compound C has two stereogenic centers but it contains
a plane of symmetry, and is achiral; C is a meso
compound.
The Three Stereoisomers of
2,3-dibromobutane

• Because one stereoisomer of 2,3-dibromobutane is

superimposable on its mirror image, there are only three
stereoisomers, not four.
R and S Assignments in Compounds with Two or
More Stereogenic Centers.

• When a compound has more than one stereogenic

center, the R and S configuration must be assigned to
each of them.

One stereoisomer of 2,3-dibromopentane

The complete name is (2S,3R)-2,3-dibromopentane
 Physical Properties of Stereoisomers
• Since enantiomers have identical physical properties, they cannot
be separated by common physical techniques like distillation.
• Diastereomers and constitutional isomers have different physical
properties, and therefore can be separated by common physical
techniques.
Fischer projection formulas.
 Cis/Trans Isomers

Stereoisomers of Disubstituted
Cycloalkanes
 Cis/Trans 1,2-dimethylcyclopentanes
• There are two different 1,2-dimethylcyclopentanes—one having
two CH3 groups on the same side of the ring and one having
them on opposite sides of the ring.

• A and B are stereoisomers.

 Cis/trans Isomers
• Stereoisomers are isomers that differ only in the way the
atoms are oriented in space.
• The prefixes cis and trans are used to distinguish these
isomers.
• The cis isomer has two groups on the same side of the
ring.
• The trans isomer has two groups on opposite sides of the
ring.
Naming Rules for Disubstituted Cycloalkanes
• Each of the cis and trans isomers of a disubstituted
cyclohexane, such as 1,4-dimethylcyclohexane, has two
possible chair conformations.

• Cis and trans isomers are named by adding the prefixes cis
and trans to the name of the cycloalkane. Thus, the cis isomer
would be named cis-1,2-dimethylcyclopentane, and the trans
isomer would be named trans-1,2-dimethylcyclopentane.
• All disubstituted cycloalkanes with two groups bonded to
different atoms have cis and trans isomers.
 Cis/Trans 1,3-disubstituted Cycloalkanes
• Consider 1,3-dibromocyclopentane. Since it has two
stereogenic centers, it has a maximum of four stereoisomers.

• Recall that a disubstituted cycloalkane can have two

substituents on the same side of the ring (cis isomer, A) or on
opposite sides of the ring (trans isomer, B). These
compounds are stereoisomers but not mirror images.
 cis-1,3-dibromocyclopentane

• To draw the other two stereoisomers if they exist, draw mirror

images of each compound and determine whether the
compound and its mirror image are superimposable.

• The cis isomer is superimposable on its mirror image, making

the images identical. Thus, A is an achiral meso compound.
 trans-1,3-dibromocyclopentane
• The trans isomer is not superimposable on its mirror image,
labeled C, making B and C different compounds. B and C are
enantiomers.

• Because one stereoisomer of 1,3-dibromocyclopentane is

superimposable on its mirror image, there are only three
stereoisomers, not four.
Skip problems 30, 31, 32, 61, 62 d,c
Chemical Properties of Enantiomers
• Two enantiomers have exactly the same chemical properties except
for their reaction with chiral non-racemic reagents.
• Many drugs are chiral and often must react with a chiral receptor or
chiral enzyme to be effective. One enantiomer of a drug may
effectively treat a disease whereas its mirror image may be
ineffective or toxic.
Chemical Properties of Enantiomers
Actually because of
priority rules a few are R,
but they all have this
configuration.
Proteins