Chapter 5 Lecture Slides PDF

Chapter 5: Stereoisomerism
Hello
Chapter 5: Stereoisomerism
Topics:
I. Overview of Isomerism
II. Introduction to Stereoisomerism
III. Designating Configuration Using the Cahn-Ingold-Prelog
System (R-S System)
Hello
IV. Optical Activity
V. Stereoisomeric Relationships: Enantiomers and Diastereomers
VI. Symmetry and Chirality
VII. Fischer Projections
VIII. Conformationally Mobile Systems
IX. Chiral Compounds that Lack a Chiral Center
X. Resolution of Enantiomers
XI. E and Z Designations for Diastereomeric Alkenes
2
Introduction to Stereoisomerism
• Drugs can cause multiple physiological responses in your body

• A drugs biological activity is based off of several
characteristics:
• acid-‐base
Hello properties
• solubility
• conformational flexibility
• Three dimensional structure.
• same connectivity of atoms, different spacial
arrangement (stereoisomers)
• Important since drugs interacting with your
body is like a lock and key type mechanism
• Need EXACTLY the correct shape
SecIon 5.4 PrecipitaIon ReacIons
4
• Isomers are different compounds that have the same formula
• There are two general types of isomers
Hello
Diﬀerent Connec4vity Same Connec4vity

Me
H H
H O H H Me
C C C H
C O
H H H H Me Me
H H
dimethylether ethanol trans cis
(all atoms s4ll connected to the same atoms)

• Although the two molecules below have the same connectivity,

they are NOT identical. So they are stereoisomers
Hello
cis-‐1,2-‐dimethylcyclohexane trans-‐1,2-‐dimethylcyclohexane
(both groups in same side of ring) (Both groups on opposite sides)
• In order to give these compounds unique IUPAC names, we use
the cis and trans prefixes
• C=C bonds do NOT rotate! They are locked in place!
• Need to maintain orbital overlap in the pi bond
• Although the two molecules

below have the same
Hello
connectivity, they are NOT
identical… they are
stereoisomers
cis-‐2-‐butene trans-‐2-‐butene
Groups on same side of pi bond Groups on opposite sides
Identify the following pairs as either constitutional isomers,
stereo isomers, or identical structures.
OH
a. HO d.
Hello
OH OH
b. HO e.
OH
O
O
c.
Answers
OH
a. HO d.
identical (you can
Hello do a chair flip) identical (vertical flip)
OH OH
b. HO e.
stereoisomers OH
stereoisomers
Same connectivity (cis-‐trans isomers)
O Same Connectivity
O
(can NOT rotate C=C bonds)
c.
Constitutional isomers
Different Connectivity
Identify the following as cis, trans, or neither
OH
a. d.
Hello
OH
OH
b. e.
HO
c. f.
Answers
OH
a. cis d. trans
Hello OH
OH
b. cis e. neither
HO
c. trans f. neither
Types of Stereoisomerism

Cis-‐Trans Isomerism: Same side vs opposite side of a ring or
double bond.
Optical isomerism: Hello

Isomers that have opposite effects on
polarized light.
• Can either rotate polarized light right or left
• Only occur if the isomers are enantiomers or mirror images
of each other but NOT the same compound.
• Your right hand and left hand are enantiomers of one
another!
A Human Hand Exhibits a Nonsuperimposable Mirror Image
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Chiral Organic Molecules
Hello
• These ARE NOT the same molecule, you can not superimpose
them anymore then you can with your right and left hands!
• Both molecules are chiral and enantiomers to one another.
★ A chiral carbon has 4 different things attached to it.
• If less than 4, it will not have a non superimposable mirror
image
• To identify such stereoisomers, we must be able to identify chiral
molecules
• A chiral object is asymmetric, which means it is not the same as its
mirror image (i.e. Hello
not superimposable on its mirror image)
• You can test whether two objects are identical by seeing if they are
superimposable.
★ Chirality most often results when a carbon atom is bonded to 4
unique groups of atoms.
Hello
• At home, make a handheld model of both of these to prove
to yourself that they are NOT superimposable!
• Can you rotate one of the molecules in your minds eye to
prove it to yourself a different way?
• Chirality is important in molecules.
– Because two chiral molecules are mirror images, they will have
many identical properties, but because they are not identical,
their pharmacology
Hellomay be very different
• Visualizing mirror images of molecules and manipulating them in

3D space to see if they are superimposable can be VERY
challenging, so…
…It is absolutely critical that you use handheld models as visual
aids
• When an atom (like carbon) forms a tetrahedral center with 4

different groups attached to it, it is called a chirality center
• Analyze the attachments for each chiral center below

Hello
each highlighted carbon
is bonded to 4 different
groups, and is a
chirality center
How many chiral centers are in each of the following molecules?
OH
a. HO c. HO
Hello
b. d.
Answers:
This central carbon is bonded to two identical carbons OH
a. HO c. HO *
Hello *
no chiral centers
two chiral centers
Not chiral!, this carbon is connected to two methyl groups
* *
b. d. * *
two chiral centers two chiral centers

How many chiral centers are in vitamin D3?
Hello
Answers: Vitamin D3 has 5 chiral (or stereogenic) centers.
Hello
*
* * * *
II. Enantiomers
• Some stereoisomers can also be classified as enantiomers

• Enantiomers are TWO molecules that are MIRROR IMAGES but are
not superimposable, therefore not identical
• Only a chiral compound can have an enantiomer
Hello
Cl
this is a chiral compound… … the mirror image will be its enantiomer
II. Enantiomers
• Some stereoisomers can also be classified as enantiomers

• Enantiomers are TWO molecules that are MIRROR IMAGES but are
not superimposable, therefore not identical
• Only a chiral compound can have an enantiomer
Hello
Cl
this is a chiral compound… … the mirror image will be its enantiomer
• Another, often easier way to draw the enantiomer of a chiral
compound is to invert the dashes and wedges of a chirality center
Hello
enantiomers enantiomers
Are these enantiomers?
NO! This is not a chiral compound, so inverting the

dashes/wedges provides an identical structure
Draw the enantiomer for the following compounds:
OH O
H
N
HO O N O
H N
HO
Hello OH
HO
a. b. c.
OH H
H O
HO N
CH3 N
Cl
NH OH
HO N
d. e. f. g.
Answers: Often drawing the mirror image is always easiest,
however, if there is only one or two sterocenters you can get
away with reversing the wedge and/or dash.
OH
H Hello H
OH OH
H
N N N
HO OH or HO
HO OH HO
a.
or
O N N O O N
H H H
OH OH OH
b.
Answers: Often drawing the mirror image is always easiest,
however, if there is only one or two sterocenters you can get
away with reversing the wedge and/or dash.
O O O
N
O Hello O
N
or
N
O
HO OH HO
c.
OH OH OH
H H H
HO N N OH HO N
CH3 H 3C or CH3
HO OH HO
d.
Answers continued.
O O O
e. or
Cl Cl Cl
NH HN NH
Hello
H H H
f. N N or N
N N N
g.
OH HO
III. Designating Configuration Using the Cahn-Ingold-
Prelog System (R-S System)
• Enantiomers are different compounds, so they must not have
identical names
• They have opposite configuration at their chirality center(s)
Cl
Hello Cl
R S
• We use the Cahn-‐Ingold-‐Prelog system to designate each chirality

center as having either the “R” or “S” configuration.
• If a compound has the “R” configuration at a chirality center, then
the enantiomer will have the “S” configuration
III. Designating Configuration Using the R-S System
• “R” or “S” is assigned to a chirality center using a stepwise
procedure
1. Using atomic numbers, prioritize the 4 groups attached to the

chirality center
Hello(1, 2, 3 and 4)
2. Arrange the molecule in space so the lowest priority group
faces away from you (pretend you are holding the lowest
priority group from behind)
3. Count the group priorities 1…2…3 to determine whether the
order progresses in a clockwise or counterclockwise direction
4. Clockwise = R and Counterclockwise = S
• A handheld model can be a very helpful visual aid for this process
• The Cahn, Ingold and Prelog system
1. Using atomic numbers, prioritize the 4 groups attached to the

chirality center. The higher the atomic number, the higher the
priority Hello
The atom with the largest atomic number is assigned the highest
priority (1), and so on…

2. Arrange the molecule in space so the lowest priority group
faces away from you (I call this a horizontal flip)
Hello
**This is the step where it is most helpful to have a handheld
model
• You can do a vertical flip, a horizontal flip, or simply rotate the C-‐C
bond, bond rotation method, until the H points backwards. They all
work okay. Note: in this case only the horizontal flip will put the H in
the back, othertimes, it will only be the vertical flip.

3. Counting the other group priorities, 1…2…3, determine
whether the order progresses in a clockwise or
counterclockwise direction
Hello
4. Clockwise = R and Counterclockwise = S
and so we just determined this chirality

Center has the (S) configuration
How do we determine the priority in this case??
H OH
Hello
• When the groups attached to a chirality center are similar, it can
be tricky to prioritize them
• Analyze the atomic numbers one layer of atoms at a time
4 1 4 1
Hello
2 3
2 3
Tie

The 1 and 4 groups are obvious, but So we have to compare the atomic
there is a tie for priority 2 and 3 weights of the atoms bonded to each
carbon to break the tie
• Analyze the atomic numbers one layer of atoms at a time
4 1
• First layer
Hello
Tie The priority is based on
the first point of
difference!
• Second layer
3
2
• When prioritizing for the Cahn, Ingold and Prelog system, double
bonds count as two single bonds
Hello
• Handheld molecular models can be very helpful when arranging

the molecule in space so the lowest priority group faces away
from you
• Here are some other tricks that can use
– Switching two groups on a chirality center will produce its
Hello
opposite configuration
• Switching two groups on a chirality center will produce its
opposite configuration
• You can use this trick to adjust a molecule so that the lowest
priority group faces away from you
Hello
• With the 4th priority group facing away, you can designate the
configuration as R
• Switching two of the groups, twice, returns the original
configuration but allows us to put the 4 priority group pointing
away. I call this trick either a horizontal flip or
vertical flip based on what I need to do.
Summary of Steps
Hello
Assign the configuration of the chiral center in the following
compound.
Hello
Answers: First label the priority of the groups. In this case, the H is
lowest priority and I left it unlabeled.
3
2 S
Hello
1
We can do a horizontal flip(shown on the next slide), a C-‐C bond
rotation(shown on the next slide), the 1, 2, 3 method but instead
of R we assign S since the H is not pointing back, or the 3, 2, 1
method to give us a clockwise S. (If you are are easily confused,
AVOID 3,2,1 and only use methods that count 1,2,3)
O
Answers Continued O
HO 3 S 2 OH
Horizontal
NH2 Flip 1 NH2
OH HO
OH OH
After a horizontal flip of Hello

the molecule so the H is in the back, and
labeling priority, counterclockwise 1, 2, 3 indicates S.
O
H2N1
S 3
HO
HO 2
rotate the bond so
H H
NH2 the H is in the back OH
OH O
OH
OH
After rotating the C-‐C bond until the H is in the back, and labeling
priority, counterclockwise 1, 2, 3 indicates S
Each of the following compounds possess carbon atoms that are
chiral centers. Locate each of these chiral centers and identify the
configuration of each one.
O
OH Cl Br Cl
H
N Hello O OH NH
O
Cl Br
a. b. c.
OH
H
H OH
O N
HO S Cl HN O
O O2N
O
N
H Br
H
Cl Cl
d. e. f.
Answers: First find the chiral centers in each molecule.
Remember, if there is symmetry the carbon in question is not
chiral. (I labeled all the chiral centers below with an *)
O
OH Cl Br Cl
H
N Hello O OH NH
* * * *
* * O
Cl Br
a. b. c.
OH
H
O H * * OH
N *
HO S * O * * Cl HN O
* * O O2N
* N
H Br
H
Cl Cl
d. e. f.
Answers: As you know, there are many correct methods to do this,
I am only going to show you one method per compound.
OH This one is easy since the lowest priority group, the
1 H H, is pointing back both times.
3 2 N
2 1
3
Hello
Left Stereocenter: 1, 2, 3 is clockwise = R
Right Stereocenter: 1, 2, 3, is counterclockwise = S
a.
Left Stereocenter: After determining priorities, I like to

pretend I grab onto priority 4 hold it in the back so the
1 2
rest of the molecule is pointing right at me. I also
Cl Br Cl recommend looking at the molecule in your minds eye
3
2 from the left side.
3 4 Counting 1, 2, 3 is counterclockwise = S
Cl Br 1
Right Stereocenter: H is pointing up so I like to do the 3,
b.
2, 1 rule instead. 3, 2, 1 gives me clockwise = R
Answers: As you know, there are many correct methods to do this,
I am only going to show you one method per compound.
O
Left Stereocenter: H is already in the back
O 1OH NH 1, 2, 3 is counterclockwise = S
2 Right Stereocenter: H is forward, so I will use
1 3 Hello O
2 3,2,1 method so I don't have to flip or rotate
3 the molecule.
c. 3, 2, 1 is clockwise = R
H is forward for all of them so I will only be using the
O
H
H 3, 2, 1 method so I don't have to get the H in the
2 1N
HO 3 back.
S 3
1 22 1 O
3 N Left Stereocenter: 3, 2, 1 = counterclockwise = S

H
H
Right Stereocenter: 3, 2, 1 = counterclockwise = S
Top Stereocenter: 3, 2, 1 = clockwise = R
d.
Left Stereocenter: H is up so 3, 2, 1 = clockwise = R
Middle Stereocenter: Lowest priority methyl group is back
1, 2, 3 is clockwise = R
2 3 Right Stereocenter: H is up so I will use 3, 2, 1 method so I
3 1 don't have to rotate anything.
2
2
3 2 4 1O 1 3 Cl
1
3, 2, 1 = counterclockwise = S
Hello
Br
Top Stereocenter: H is up so I will use 3, 2, 1 method so I
e. don't have to rotate anything.
3, 2, 1 = counterclockwise = S
OH
1
3 22 3 OH Left Stereocenter: H is back so 1, 2, 3 = clockwise = R
1
HN O Right Stereocenter: H is back so 1, 2, 3 = clockwise = R
O2N
f. Cl Cl
5.3 (R) and (S) in IUPAC Nomenclature
• The (R) or (S) configuration is used in the IUPAC name for a
compound to distinguish it from its enantiomer
Copyright © 2017 John Wiley & Sons, Inc. All rights reserved. 50 Klein, Organic Chemistry 3e
• Because the structures of enantiomers only differ in the same
way your right hand differs from your left, they have the same
physical properties.
Hello
• Enantiomers only differ in (1) how they interact with other chiral
compounds, and (2) their optical activity
Unpolarized Light Consists of Waves Vibra4ng in Many Diﬀerent Planes
Hello
The Rota4on of the Plane of Polarized Light by an Op4cally Ac4ve Substance
Hello
Op4cal Ac4vity
▪ Exhibited by molecules that have nonsuperimposable
mirror images (chiral molecules).
▪ Enantiomers: Isomers of nonsuperimposable mirror
Hello
images. (each enantiomer rotates light in the opposite
direction)
FYI
If a molecule has an enantiomer, or a nonsuperimposible mirror
image, then we say that the molecule is chiral.
If a molecule is chiral, then it will rotate the plane of polarized
light. (All these definitions are connected)
• Enantiomers will rotate the plane of the light to equal degrees
but in opposite directions
• The degree to which light is rotated depends on the sample
concentration and the pathlength of the light
• Standard optical Hello rotation measurements are taken with 1 gram of
compound dissolved in 1 mL of solution, and with a pathlength of
1 dm for the light
Temperature and the wavelength of temperature

light can also affect rotation and must
be reported with measurements that wavelength
are taken
• Consider the enantiomers of 2-‐bromobutane
Hello
• (R) and (S) refer to the configuration of the chirality center
• (+) and (−) signs refer to the direction that the plane of light is
rotated
• (+) rotation is called dextrorotary, and (−) is levorotary
• The compound below has the (S) configuration
Hello
• Its optical rotation is levorotatory (−) at 20°C, but it is
dextrorotatory (+) at 100°C
• There is no correlation between R/S and +/−

• The magnitude and direction of optical rotation cannot be

predicted, and has to be measured experimentally
• However, we can Hello

predict the rotation of a racemic mixture to be
0˚ (the optical rotation of each enantiomer cancels each other).
• Racemic mixture: 50/50 mixture of two enantiomers
• If one enantiomer is present in excess, relative to the other, then
the mixture will have an optical rotation, but it will be less than
the pure enantiomer.
Racemic mixture: Both isomers exist with equal abundance

(1:1 ratio) so the plane of light is not rotated
• Each enantiomer has an opposite effect so they cancel
each other out
Hello
• For unequal amounts of enantiomers, the enantiomeric excess

(% ee) can be determined from the optical rotation
R S
Hello
• Suppose a mixture of (R) and (S) 2-‐bromobutane has a specific
rotation of −4.6 ˚. This allows us to determine the % ee
• So, (−4.6) / (−23.1) x 100% = 20 % ee of the R enantiomer

What is enantiomeric excess (ee)?
OH
80% Hello
OH
20 %
80 − 20 = 60% ee

Miscellaneous Vocabulary:
Polarization: The direction of the oscillating electric field that propagates
through space.
• Light from the sun
Hello is polarized all all different directions
Plane-‐polarized light: When light passes through a filter and is only polarized
in one direction, like with polarized sunglasses.
Optically active: A substance that will rotate the plane of polarized light.
• Any chiral compound will do this as long as the enantiomers are NOT in
a 1:1 ratio.
Optically inactive: A substance that will NOT rotate the plane of polarized
light. (Substance is racemic or has no chiral centers)
Polarimeter: The device we use to measure the rotation of polarized light.
Specific rotation = [α] = standardized value

observed rotation = α = experimentally obtained, use math to
convert the observed rotation to the specific rotation
-‐ depends on bHello
oth temperature and wavelength
path length = l = how far light travels through a sample (in dm)
concentration = c in g /mL α
Specific rotation = [α] = c x l
[observed α]
% ee =
[pure α]
Levetiracetam is used for the treatment of O
seizures in patients with epilepsy. It is known
that a pure sample has a specific rotation of NH2
−93.4 at 20°C. O

N
Hello
You make some Levetiracetam in lab and want to determine what
enantiomer you made and the % ee. You take a 500 mg sample,
dissolve it in 10.0 mL acetone and put it in a polarimeter with a
path length of 10.0 cm and observe α = +3.56°. Determine if you
made Levetiracetam or its enantiomer and determine the % ee.
O
1. A positive specific rotation indicates that
we primarily synthesized the enantiomer NH2
of levetiracetam. O
N
93.4 = α
Hello α = 4.67 for a pure sample
.0500g/cm x 1.00 dm
α
Specific rotation = [α] = c x l
% ee = 3.56
= 76%
4.67 [observed α]
% ee =
[pure α]
V. Stereoisomeric Relationships: Enantiomers and
Diastereomers
• Categories of isomers
Hello
• Enantiomers: stereoisomers that are mirror images

• Diastereomers: stereoisomers that are not mirror images
s areV.stereoisomers that are mirror
Stereoisomeric images of one another,
Relationships: while diastereomers
Enantiomers and are s
are not Diastereomers
mirror images of one another. According to these definitions, we can under
s isomers (discussed at the beginning of this chapter) are said to be diastereomers,
• Consider
omers. Consider,the
once structures
again, theostructures
f cis-‐ and oftrans-‐2-‐butene
cis-2-butene and trans-2-butene:
H3C CH3 H3C H
H H H CH3
cis-2-Butene trans-2-Butene
Hello
• They abut
reoisomers, re sthey
tereoisomers, but images
are not mirror not mirror
of one images
another of and
each
areother. So, dias
therefore
they
mportant are diastereomers!
difference Recall that
between enantiomers andenantiomers
diastereomershave is thatidentical
enantiomers
hysicalphysical
properties properties.
(as seen in Section 5.4), while diastereomers have different ph
as seen in Section 5.1).
• Diastereomers have different physical properties
fference between enantiomers and diastereomers becomes especially relevant when w
unds containing more than one chiral center. As an example, consider the following stru
We rarely call these diastereomers, OH
we tend to save that term for
compounds with more than one s1tereocenter. Instead we call these
geometric isomers or cis-‐trans i2somers
Me .
re has two chiral centers. Each one can have either the R configuration or the S confi
Diastereomers
• Consider a cyclohexane with three substituents
Hello
• There are three stereocenters here, and so there are 8 possible
stereoisomers (all drawn above). Consider the relationship
among them (enantiomers vs. diastereomers)
Two compounds in the same box are enantiomers (mirror images), if they
are in different boxes, they are diastereomers (not mirror images)
Diastereomers
• Notice these 8 stereoisomers are comprised of 4 pairs of enantiomers
Hello
Can think of this as a family where there are 4 pairs of twins, for a total
of 8 kids. Each kid has 7 siblings, where one of them is their twin (i.e.
enantiomer) and the other 6 are diastereomers
Diastereomers
• The number of possible stereoisomers for a compound depends
on the number of chirality centers (n) in the compound
Maximum number of stereoisomers = 2n
• What is the maximum

Hello number of possible cholesterol isomers?
Diastereomers
Answers:
• The number of possible stereoisomers for a compound depends
on the number of chirality centers (n) in the compound
Hello
• What is the maximum number of possible cholesterol isomers?
Answers: 8 stereocenters possible so 28 or 254 possibilities.

However, nature only makes the one possibility listed above.
Diastereomers
Determine if the following pairs of compounds are enantiomers
or diastereomers
OH OH OH OH
Cl
e.
a. OH OH Cl
Hello
b. f.
OH OH
c. g.
d.
Diastereomers
Answers
The chiral center on the right stayed
OH OH
the same while the other two chiral
a.
centers changed. Diastereomers
OH OH
Hello If you cant rotate the bonds in the

3 molecule in your head, determine R or
3 2 11 3
b. 2 11 2 R S for each stereocenter. Then solve.
S 3S 2R Both sterocenters in this case were
inverted: Enantiomers
R S If you do a horizontal flip of the molecule on
c. the right, you will see it is a mirror image of
R S the molecule on the left. Enantiomers.
Labeling the stereocenters will give you the
R S same answer, it will just take longer.
d.
S S One is cis, the other is trans. It must be
Diastereomers
Diastereomers
Answers
If you can, rotate the central C-‐C bond in an
OH OH attempt to make the two molecules
R superimposable. The Cl will be dashed, not
R S
Cl
d. R
wedged so they are diastereomers. Labeling
Cl
Hello the stereocenters will tell you the same thing.
e. S R If you can rotate the C-‐C bond in your head

R R
great! If not, assign R and S. Diastereomers
OH OH
f. They are NOT mirror images of one another.
RS S S They must be diastereomers. You do not
R R need to determine the R’s or S’s but I did for
your convenience
• Any compound with only ONE chirality center will be a chiral
compound
• With more than one chirality center, a compound may not be
chiral; it may have a plane of symmetry
• Consider the stereoisomers
Hello below, which possess TWO chirality
centers:
trans-‐1,2-‐dimethylcyclohexane cis-‐1,2-‐dimethylcyclohexane
• The trans isomer is chiral, but the cis isomer is not (it is achiral)
Hello
• If a molecule has a plane of symmetry, it will be achiral
The cis isomer has a plane of symmetry, which

means it will be superimposable on its
mirror image, and is not a chiral compound
• Molecules with an even number of chirality centers

that have a plane of symmetry are called meso
compounds
★ Another way to tHello est if a compound is meso is to
see if it is identical to its mirror image (This
method works best for me)
• Draw the mirror image of the cis isomer and show that it can be
superimposed on its mirror image
• By definition, when a compound is identical to its mirror image,

it is NOT chiral. It is achiral
• A compound with chirality centers, but is achiral because of

symmetry is called a meso compound
• The molecules below are meso compounds:

Hello
• meso compounds have less than the predicted number of

stereoisomers based on the 2(n) formula
• If a compound has a plane of symmetry, it is ACHIRAL
• But… a compound that lacks a plane of symmetry may still be an
achiral compound… if it has an reflectional symmetry through
inversion about Hello
a central point in the molecule
• The molecule to the right has two chirality

centers, and no plane of symmetry, but it is
still achiral because of inversion

★ It’s mirror images is still the same molecule!

• OVERALL:
• The presence or absence of rotational symmetry is

irrelevant to chirality
Hello
• A compound that has a plane of symmetry is achiral
• A compound without a plane of symmetry will

usually be chiral, but there are exceptions (such as a
compound with an inversion center).
★ If a molecules mirror image is identical and
superimposable to the original structure, it must be
achiral (easiest method for me)
Draw all the possible isomers for this compound. Label the
enantiomers and Diastereomers
Hello OH
OH
Answers:
• meso compounds have less than the predicted number of
stereoisomers based on the 2(n) formula
OH OH OH OH
Hello =
OH OH OH OH
a. b. c. d.
pair of enantiomers identical compound

2n does NOT work, it predicts 4 possible isomers, instead there
are only 3.
a. and b. are enantiomers
a. and c. are diastereomers
a. and d. are diastereomers.
c. and d. are the same compound. (you didn’t have to show this)
Draw all the possible stereoisomers for this compound
OH
HO OH
OH
Hello
a. c. d.
d. e.
Answers
a.
Enantiomers These two are the same (Meso)
Hello
b. OH OH OH OH OH
OH OH OH OH OH
Enantiomers These two are the same (Meso)
HO OH HO OH
HO OH
c. HO
Enantiomers
OH
These two are the same (Meso)
HO OH
Answers
d.
Hello
Enantiomers
e.
Enantiomers
• Fischer projections can also be used to represent molecules with
chirality centers
• Horizontal lines represent attachments coming out of the page

Hello
• Vertical lines represent attachments going back into the page
• Fischer projections are most useful when drawing molecules

having multiple chirality centers (like sugars, shown below).
Hello
• Fischer projections are also useful to quickly assess

stereoisomeric relationships
Hello
Determine the configuration of the chiral center in the following
compound. (as a class)
Hello O OH
H OH
CH2OH
Answer: Redraw using dashes and wedges. If H is up, use 3, 2, 1
rule, or do a horizontal flip until H is back. Then do the 1, 2, 3 rule.
O OH O OH
Draw in
Wedges and Dashes 2 H is up, use the 3, 2, 1 rule.
1
H OH Hello H OH
3 Clockwise = R
CH2OH CH2OH
Horizontal
Flip
O 2 OH
H is back, use the 1, 2, 3, rule.
1
HO H Clockwise = R
3
CH2OH
Determine the configuration of the chiral center in the following
compounds.
O OH O OH
H Hello
NH2 HO H
CH2OH CH3
a. b.
CH2OH CH2OH
HO H Br H
CH2CH3 CH3
c. d.
Answer: Redraw using dashes and wedges. If H is up, use 3, 2, 1
rule, or do a horizontal flip until H is back. Then do the 1, 2, 3 rule.
O OH O OH O OH O OH
2 2
H NH2
=
H 1NH HO H
=
HO1 H
2
CH2OH
a. 3 CH
OH
CH
b. 3
CH3
Hello2 3
H is up, use the 3, 2, 1 rule. H is up, use the 3, 2, 1 rule.
Clockwise = R Counterclockwise = S
CH2OH CH2OH CH2OH CH2OH

2 2
HO
1 H HO H Br H
1
Br H
= =
3 3
CH2CH3 CH2CH3 CH3 CH3
c. d.
H is up, use the 3, 2, 1 rule. H is up, use the 3, 2, 1 rule.
Counterclockwise = S Counterclockwise = S
Are these enantiomers and are these compounds chiral?
Hello
Not Chiral! They are two butane molecules

butane
• Molecules can rotate around single bonds.
• Recall the gauche rotational conformations of butane
Hello
• Realize that these conformations are chiral, and are actually

enantiomeric
• But, because these rotatomers are interchangeable via bond

rotation, butane is not a chiral compound.
Are these compounds chiral?
Hello
• Compare both possible chair conformations of (cis)-‐1,2-‐

dimethylcyclohexane
Hello
• These conformations are chiral, and also enantiomeric
• However, these conformations interconvert, and overall this is an

achiral compound (possesses a plane of symmetry, meso)
OH OH
=
OH OH
mirror image 2 4
5 1 3
6
3 6 5
4 2 Hello 1
A B
ring flip Rotate Molecule ring flip
4 6 mirror image
5 3 4 5
2 1
3 1 2 6
C D
A and D are in the same conformaIon; B and C are in the same conformaIon
Therfore A, B, C, and D are all the same molecule. Make a model to prove it to yourself!
IX. Chiral Compounds That Lack a Chiral Center
• ATROPISOMERS: stereoisomers that would be interchangeable

through the rotation of a sigma bond, but because the bond is unable
to rotate, the different conformations are “stuck” and not
interchangeable.
Hello
• (R) and (S)-‐BINAP are chiral, and enantiomers of one another, even
though they do not have any chirality centers (they instead have an
“axis of chirality.”
Rotational barrier is too high! The can not interchange!

IX. Chiral Compounds That Lack a Chiral Center
• ALLENES: compounds that possess two adjacent C=C double

bonds. They may or may not be chiral depending on the
substituents,
Hello
• The the two groups on each end of the allene are different, than
it will be a chiral compound
Make a model at home! Prove they are different!

Determine if each of the following allenes is chiral or achiral
H 3C
CH3 H
C C C C C C
CH3 CH3
H
a. b.
Hello
Achrial, the two methyls are the same. Achrial, each CH2 in the
cyclopentanone ring is the same
H 3C
H H
C C C C C C
CH2CH3 CH3
H
c. d.
Chiral, the two groups on
Chiral, Every group is different.
each side are different.
• Most methods of separating compounds from one another take

advantages of the compounds’ different physical properties
– Distillation – Separates compounds with different boiling

points. Hello
– Recrystallization – Separates compounds with different

solubilities.
• Such methods often don’t work to separate one enantiomer

from its racemate, because they have identical physical
properties.
• In 1847, Pasteur performed the first resolution of enantiomers

from a racemic mixture of tartaric acid salts
Hello
• The different enantiomers formed different shaped crystals that

were separated by hand using tweezers
• However, this method doesn’t work for most pairs of enantiomers
Crystallization when there is an enantiomeric excess
• If you have a mixture of enantiomers with a high % ee, often times
you can improve your enantiomeric excess through recrystallization.
• One enantiomer
Hello will often crystallize out while leaving the other
enantiomer behind in solution.
• You often sacrifice yield for purity since some of your
enantiomer will inevitably be left behind.
• If you try to get every last crystal out, the other enantiomer
will crystallize as well.
• Another method is to use a chiral resolving agent
Hello
• Chiral amine + chiral acid = diastereomers!

• The differing physical properties of diastereomers allow them to be
more easily separated
• Affinity chromatography is often used to
separate compounds
• a glass column (or tube) is packed with a

solid substance to act as an adsorbent,
Hellothrough it.
and a mixture is passed
• If a chiral adsorbent is used, then enantiomers will interact

with it differently, and travel through the column at different
rates, allowing for their individual collection (thus separation).
• Your right hand can only shake hands with another right
hand. A certain enantiomer can more efficiently stick to the
chiral compound in the column
• This is a very common way for resolving enantiomers
• For molecules with more than two different groups attached to
the C=C double bond, the E/Z notation is used instead of cis/
trans notation
Hello
Cis/trans isn’t adequate to differentiate between these two diastereomers
• cis and trans only works if there is only one (non hydrogen)
substituent on each carbon of the alkene
• Assigning E or Z to a C=C double bond:

1. prioritize the groups attached to the C=C double bond based
on atomic number (Just like when you are determining R and S)
Hello
• Assigning E or Z to a C=C double bond:

1. prioritize the groups attached to the C=C double bond based on
atomic number
2. If the top priority groups are on the same side of the C=C double
bond, it is Z (for zussamen, which means together)
Hello
If the top priority groups are on opposite sides of the C=C
double bond, it is E (for entgegen, which means opposite)
• Think ET like the movie E = trans

For each of the following alkenes, assign the configuration of the
double bond as either E or Z:
Hello
HO
Equal
C bonded to O, H H Priority
Higher
O wins out, higher Hello
Priority C bonded to C, H, H
molecular weight HO Lower C bonded to C, H, H
Priority
Lower Higher C bonded to C, C, H

C bonded to C, C, C Priority Priority C counts twice due to
Equal double bond
Priority
C bonded to C, H, H
The alkene is E

Hello
O
Cl
F
Answers:
Look for the highest priority. Same side = Z Opposite sides = E
Remember the movie ET E = Trans
Hello
E Z
O
Cl
F
Z Z
Higher Priority =

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Chapter 5: Stereoisomerism

• Drugs can cause multiple physiological responses in your body

Diﬀerent Connec4vity Same Connec4vity

dimethylether ethanol trans cis

(all atoms s4ll connected to the same atoms)

• Although the two molecules below have the same connectivity,

• Although the two molecules

Types of Stereoisomerism

Optical isomerism: Hello

• Chirality is important in molecules.

• Visualizing mirror images of molecules and manipulating them in

• When an atom (like carbon) forms a tetrahedral center with 4

• Analyze the attachments for each chiral center below

This central carbon is bonded to two identical carbons OH

two chiral centers two chiral centers

• Some stereoisomers can also be classified as enantiomers

• Some stereoisomers can also be classified as enantiomers

Are these enantiomers?

NO! This is not a chiral compound, so inverting the

• We use the Cahn-­‐Ingold-­‐Prelog system to designate each chirality

1. Using atomic numbers, prioritize the 4 groups attached to the

• The Cahn, Ingold and Prelog system

1. Using atomic numbers, prioritize the 4 groups attached to the

• The Cahn, Ingold and Prelog system

• The Cahn, Ingold and Prelog system

and so we just determined this chirality

How do we determine the priority in this case??

• Handheld molecular models can be very helpful when arranging

Summary of Steps

After a horizontal flip of Hello

Left Stereocenter: After determining priorities, I like to

3 N Left Stereocenter: 3, 2, 1 = counterclockwise = S

Temperature and the wavelength of temperature

• Consider the enantiomers of 2-­‐bromobutane

• (+) rotation is called dextrorotary, and (−) is levorotary

• The compound below has the (S) configuration

• There is no correlation between R/S and +/−

• The magnitude and direction of optical rotation cannot be

• However, we can Hello

• Racemic mixture: 50/50 mixture of two enantiomers

Racemic mixture: Both isomers exist with equal abundance

• For unequal amounts of enantiomers, the enantiomeric excess

• So, (−4.6) / (−23.1) x 100% = 20 % ee of the R enantiomer

What is enantiomeric excess (ee)?

80 − 20 = 60% ee

Specific rotation = [α] = standardized value

−93.4 at 20°C. O

• Enantiomers: stereoisomers that are mirror images

Maximum number of stereoisomers = 2n

• What is the maximum

Answers: 8 stereocenters possible so 28 or 254 possibilities.

Hello If you cant rotate the bonds in the

e. S R If you can rotate the C-­‐C bond in your head

The cis isomer has a plane of symmetry, which

• Molecules with an even number of chirality centers

• By definition, when a compound is identical to its mirror image,

• A compound with chirality centers, but is achiral because of

• The molecules below are meso compounds:

• meso compounds have less than the predicted number of

• If a compound has a plane of symmetry, it is ACHIRAL

• The molecule to the right has two chirality

★ It’s mirror images is still the same molecule!

• The presence or absence of rotational symmetry is

• We use the Cahn-‐Ingold-‐Prelog system to designate each chirality

• Consider the enantiomers of 2-‐bromobutane

e. S R If you can rotate the C-‐C bond in your head

• Compare both possible chair conformations of (cis)-‐1,2-‐