Chem 201/Beauchamp Topic 7, Stereochemistry 1 Chem 201/Beauchamp Topic 7, Stereochemistry 2

Isomer Overview Essential Vocabulary of Stereochemistry – terms to know for this topic
The following table summarizes the various types of isomers we will encounter as we proceed through organic Chiral center – a tetrahedral atom with four different groups attached, a single chiral center is not superimposable
chemistry. on its mirror image, also called a stereogenic center, and asymmetric center

Isomers - compounds that Stereogenic center – any center where interchange of two groups produces stereoisomers (different structures), could
have the same formula be a chiral center producing R/S differences, or an alkene producing E/Z differences or cis/trans in a ring

Absolute configuration (R and S) – the specific 3 dimensional configuration about a tetrahedral shape, determined
by assigning priorities (1-4) based on the highest atomic number of an atom at the first point of difference. When the
Constitutional or structural Stereoisomers have their atoms lowest priority group is away, a circle is traced through the highest 3 priorities (1  2  3) in a clockwise direction
isomers have their atoms attached with the same connectivity,
joined together in different but differ in their arrangements in (= R) or a counterclockwise direction (=S)
arrangements space
E/Z Nomenclature – a system to unambiguously identify the stereochemistry at alkenes based on the priorities of the
attached groups at each carbon. E has the highest two priority groups on the opposite side of the double bond and Z
functional
has the highest two priority groups on the same side of the double bond.
chain or skeletal positional
isomers isomers group isomers
Chiral Molecules – a molecule that is not superimposable upon its mirror image
Cl O

butane 1-chloropropane
OH Achiral Molecules – a molecule that is superimposable upon its mirror image
Cl H
propanal prop-2-en-1-ol Enantiomers – stereoisomers that are different mirror images of one another, there can only be one enantiomer
(allyl alcohol)
(aldehyde)
O O Diastereomers – stereoisomers that are not mirror images of each other, can be a result of either (R/S) differences,
2-methylpropane 2-chloropropane (E/Z) differences in alkenes, cis/trans differences in rings or any combination of all those kinds of differences; there
oxatane may be many, many diastereomers.
propanone (cyclic ether)
(ketone) Meso Compounds – compounds that contain two or more chiral centers, yet are identical with their mirror images
(they are achiral and optically inactive). A mirror plane cuts through the middle of the molecule.

Optical Activity – angle of rotation of plane polarized light using a polarimeter as it passes through a solution of
chiral compound, achiral compounds do not rotate plane polarized light and are optically inactive (no rotation).

Enantiomers are mirror

d (+) = dextrorotatory – clockwise rotation of plane polarized light in a polarimeter (only with chiral compounds)
Conformational isomers Diastereomers are
differ by rotation about a image reflections that stereoisomers that l (-) = levorotatory – counterclockwise rotation of plane polarized light in a polarimeter (only with chiral compounds)
single bond and are usually are not superimposable are not mirror images
easily interconverted. (different). of one another. Racemic Mixture – a equal mixture of two enantiomers. Racemic mixtures are optically inactive even though
a. CH3 CH3 CH3
there are chiral molecules present. Each enantiomer cancels out the optical rotation of the other enantiomer.
OH OH
fast H C OH H C OH HO C H Fischer Projections – a method for representing stereogenic centers in chains, with the stereogenic carbon at the
fast C C vs.
CH3CH2 H2CH3C intersection of vertical and horizontal lines, the horizontal lines are consider to be coming forward in front of the
H H H C OH H C OH HO C H
H3 C CH3 plane (wedges) and the vertical lines are considered to be going backward behind the plane (dashes).
CH3 CH3 CH3
CH3 CH3 Haworth Projections – a method for representing cyclic structures, drawn flat with vertical lines to show top and
H H meso (dl) enantiomers
b. bottom faces of the ring, analogous to Fischer projections for straight chains. Commonly used for cyclic sugars in
fast biochemistry.
H CH3 CH3 H
E or trans Z or cis Prochiral – molecules are those that can be converted from achiral to chiral in a single step (re and si faces).
(dl) or () enantiomer pairs also called
H CH3
H H geometric Enantiomeric excess (ee) is a measure for how much more of one enantiomer is present compared to the other
isomers and
cis/trans isomers (50% ee in R is 75% R and 25% S)

CH3 CH3 CH3 H Other types of chirality include axial (helical) chirality (allenes, DNA) and planar chirality (E-cyclooctene).
cis trans
Chem 201/Beauchamp Topic 7, Stereochemistry 3 Chem 201/Beauchamp Topic 7, Stereochemistry 4

How many butan-2-ols are there? At first, it seems there must be only one. But let’s build models and If there are no chiral centers then the mirror image structures are really identical, and this leads to no net
compare. observed rotation of polarized light (any right rotation is cancelled by an equal amount of left rotation).
mirror plane
OH OH OH
1 1
H2
H3C C C CH3 C C Both mirror images are
H H
CH3 H3C identical (achiral) - no net
CH2 H2 C C C 3 rotation of light.
H H3C CH3 3

S absolute configuration R absolute configuration 3 2 2

2D representation 3
of butan-2-ol 3D representation of butan-2-ol
reveals two different mirror images
(called enantiomers) Molecular models you always carry with you – They’re called hands!

Three dimensional structures of 2-butan-2-ol reveal that there are two different butan-2-ols which are mirror This subtle difference in structure can be very difficult to visualize on paper or even with models. However, it
images of one another. Different mirror images are called enantiomers. This property can be observed in turns out that nature gave us the perfect tools to consider this difficult 3D problem. Those tools are called hands
enantiomeric molecules using plane polarized light. Rotation of plane polarized light can rotate either to the right (and of course, we have our minds)! Our hands can reveal some of the problems we face in working with
(dextrorotatory = d = +) or to the left (levorotatory = l = -) depending on the substance. Such samples are called enantiomers, and some of the solutions to those problems. Many of us will have a problem picturing abstract
‘optically active’ and have a similar relationship to one another as your left and right hands. molecules in space, especially different mirror image molecules. Almost none of us will have a problem picturing
The property of handedness will be observed at any tetrahedral center with four different groups present. mirror image hands, because of our lifetime experience using them.
Let’s draw the outline of a hand. If we don’t use more specific nomenclature, we wouldn’t know if the hand is
chiral center 1 1 chiral center a right hand or a left hand? Either of your hands would fit in the first trace of a hand below. What further
(stereogenic) (stereogenic) These are different mirror images
and called enantiomers.
information do we need? We could say “right” or “left”, or we could add some additional details to our drawings.
C C
4 4 # # = priorioty of groups attached to chiral center,
2 2 (1 > 2 > 3 > 4), discussed later in text.
3 3
Determines absolute configuration as R
(R)-absolute configuration mirror (S)-absolute configuration (rectus / right) and S (sinister / left).
plane
A plain silhouette
Any tetrahedral carbon with four different groups about it is called a chiral center and a stereogenic center. In does not provide
an actual molecule, there may be only one chiral center or 10s, 100s, 1000s or more chiral centers. enough information
to tell if the hand is Added features make
1 1 face up or face down it easy to determine if
(left or right). the top or the bottom
rotate 180o of the hand is towards
you (...or you could
along center add a descriptor of left
C axis C 3 NOT mirror images.
4 hand = ? right hand left hand or right).

2 2
3 4 Our mental image of enantiomers (different mirror images) is rock solid when we’re talking about hands. We
don’t really even need a picture to distinguish right from left. From a lifetime experience of using them, we know
that our two hands, while looking similar, are very different from one another. Just try switching hands the next
If a 50/50 racemic mixture of different mirror image structures (enantiomers) is present, this will lead to no time you are taking notes in organic chemistry. Almost every detail we need to understand about molecules can be
observed rotation of polarized light because the right and left rotations cancel. modeled with your hands. You can even use your hands as approximations of tetrahedral atoms, using your arm,
1 1 thumb and first two fingers. Try it using the pictures below as an example. Use your hands to model tetrahedral
centers and this subject will be a whole lot easier.
A racemic mixture occurs when
both mirror images are present in
C C 4 equal amounts. Each rotation cancels
4
the other for no net observed rotation.
2 2
3 3
mirror
plane
Racemic mixture = 50/50 mixture of enantiomers
Chem 201/Beauchamp Topic 7, Stereochemistry 5 Chem 201/Beauchamp Topic 7, Stereochemistry 6

right hand ...or... left hand Now this was set up to be easy, the priority numbers were given and the low priority group was away. The
lowest priority group was already away from you, which made the analysis simple (and you didn’t have to assign
any priorities). In a random example, you have no guarantee that this will be the case. Also, a molecule could have
several chiral centers with a variety of viewing perspectives. You may have to redraw a structure or build a model
to be able to evaluate R or S (at every chiral center), especially if your 3D visualization skills are weak.
There is a simple alternative, however, and this will make you a pro at making stereochemical assignments. All
you need are your hands and the ability to evaluate the priorities. Let's assign the absolute configuration (R or S) in
the structure below. First, we need to assign the priorities (double check my assignments). I like to redraw the
chiral center and insert the numbers of the priorities. It’s a little extra work, but it makes me more accurate in my
answers. If we blindly traced our circle through 1  2  3, we might be tricked into thinking that the absolute
configuration shown is R, which is not the case. Our answer is wrong because we haven’t oriented the low priority
group away from our viewing perspective.
arm arm
H2
C 1
S
equivalent to
CH2 Superficially appears to be "R",
middle middle
thumb thumb H3C C 3 C but the low priority group is
finger finger
mirror O NOT away from the viewer.
pointer pointer H 2
finger images 4
finger
Wrong direction!
R and S Nomenclature (Absolute configuration as R or S)
We have to turn the molecule around (in our head, on paper, build a model...), and then evaluate the trace of the
circle. However, there is an easier, more reliable way to do this. We can make our arm and fingers into a
In addition to recognizing when enantiomers are present (stereoisomers in general), we also have to correct our
tetrahedron. The four different groups will be matched with our arm, thumb and first two fingers of either hand.
nomenclature so that it is specific enough to identify a unique structure. The rules to solve this dilemma were
The arm will always be the low priority group when that group is toward us. If the low priority group faces
created by three chemists in the mid-1950s, R.S. Cahn, C.K. Ingold and V. Prelog (CIP rules). The absolute
towards the front and is on the left side, you will use your left arm. If the low priority group faces front and is on
configuration of a chiral center was designated as R (rectus = right, Latin) or S (sinister = left, Latin). These two
your right side, you will use your right arm. Your thumb, pointer finger and middle finger will complete the
letters specify whether a stereogenic center is the "right" one or the "left" one.
tetrahedron and you will assign the appropriate number (1, 2 or 3) to the appropriate finger.
Priorities of the four different groups attached to a chiral atom are assigned, based on atomic numbers. The
higher an atomic number is, the higher the priority will be. This is easy in organic chemistry (and biochemistry),
because we only have a few atoms to consider (plus lone pairs): I > Br > Cl > S > P > F > O > N > C > H > lone pair 1
of electrons. It is possible for a single element to have different isotopes (e.g. hydrogen = H, deuterium = D and
tritium = T). In these cases, the most massive isotope is the highest in priority (e.g. T > D > H). The highest priority 3
group is specified as #1 and the lowest priority group as #4. A specific viewing perspective requires that the low 1
priority group (#4) be pointed away from the viewer (you), while the remaining three groups trace a circle from #1 
#2  #3, either clockwise (CW) or counterclockwise (CCW). When the circle traces clockwise, the absolute equivalent to
configuration is R and when the circle traces counterclockwise the absolute configuration is S. 3 C 2
2
mirror 4
plane
(enantiomers) Use the left arm and hand.
The left arm will be priority
1 1 4 4 and matches with the low
Priority numbers are based priority group facing forward.
on atomic numbers in the
4 C periodic table. The lowest 4 is on the left side
C 4 and to the front.
priority group is a lone pair
2 2 of electrons.
3 3
A convenient movement is now possible. We can turn our arm around at the elbow and look at our three
"R" absolute configuration requires that "S" absolute configuration requires that fingers with the low priority group (our arm) away from us. Of course you must remember at least which fingers
the low priority group, 4, is away from the the low priority group, 4, is away from the are 1  2 to get the correct direction of the circle you are tracing. I don’t try to remember all three because then I
viewer while a circle traced from 1 to 2 to viewer while a circle traced from 1 to 2 to get mixed up by the time I rotate my arm around. Remembering 1  2 is easier. Do not flatten out your hand
3 goes in a clockwise direction (CW). 3 goes in a counterclockwise direction (CCW).
when you turn it around. It makes it difficult to trace your circle. Keep it in a tetrahedral shape.
These two images are different mirror images and called enantiomers.
Chem 201/Beauchamp Topic 7, Stereochemistry 7 Chem 201/Beauchamp Topic 7, Stereochemistry 8

1 We now have an absolutely certain way to accurately draw or build a three dimensional representation of an sp3
center having this property of chirality (handedness). The classification of the absolute configuration at a chiral
1
center must be either R or S.
2
What if a chiral atom has four different attached groups, but two of the directly attached atoms are the same?
3 The circle traces counter We encountered just such a problem in our example of butan-2-ol. It is obvious that methyl (CH3) is not ethyl
4 C clockwise = S absolute (CH2CH3), however when we examine the atoms attached to the chiral center, we find the two carbon atoms are
3 configuration.
2 identical in priority (at the intermediate priority levels of 2 and 3).
4
OH OH 1
Turn your left arm around to rotate 4 away from you. *C *C
Remember which fingers are assigned 1 and 2 to start H H *C
the trace of your circle, counter clockwise in this example. CH2CH3 C
H3 C C C 4
?
An alternative way to make the assignment of absolute configuration is to hold one prong of a tetrahedral atom ? (2 or 3)?
* = chiral atom
from your molecular model kit with your finger tips and let it represent the chiral tetrahedral atom. Hold it in place (2 or 3)? C (C,H,H)
to model a chiral center, assign two of the prongs as 1 and 2 priorities, and then turn the tetrahedral model atom C (H,H,H)
around like it was your hand. Trace the circle using priorities 1 and 2 as your guide. The only disadvantage to this
approach is you might not have your model atom with you, but you will always have your hands and arms with Our next step in such a situation is to examine the additional bonded groups to these equivalent atoms. In the
you. case of carbon, that will mean three additional bonds to consider (the fourth bond is the attachment to the chiral
1, 2, 3 ? center). Our decision of priorities is always based on atomic number. The highest priority atom (highest atomic
number) will decide the issue, regardless of what other atoms are present. If the atoms attached in the first sphere
1, 2, 3 ?
C of atoms are equivalent then we continue to the second sphere of attached atoms for evaluation. When the
1, 2, 3 ? pathways begin to branch out in such a case, always trace the highest priority path possible until you come to a
4 difference that will distinguish one path from another. Some examples will prove helpful here.

Example 1

2-bromobutane first sphere First sphere of consideration

Turn model atom around and
make "R" or "S" assignment.
second sphere 1 = Br
2=C cannot make a decision
third sphere 3=C since both atoms are the same
What about the mirror image structure? Since the low priority group faces forward and is on the right side, Br
you will need to use your right arm. Spread the appropriate fingers to model the tetrahedral center and assign the 4=H
other priorities (1, 2 and 3). As before twist your elbow so that the low priority group (your arm) is away from you *C
H H H Second sphere of consideration
and trace the circle from 1 to 2 to 3. In this example the circle traces clockwise and the absolute configuration is R C
(as it must be because it is the mirror image of an S absolute configuration). C
H C 2 = (C,H,H) C is higher priority than
H2 H H
H2 H
C C 1 H 3 = (H,H,H) any H, so ethyl > methyl
S S H
CH2 H2C =
C 3 1
H3C C C CH3
O O 2
H H 4 Circle traces CW = R, so this
* = chiral center *C
(S)
mirror
(?) Since the low priority group is in the right 4 structure is 2R-bromobutane.
plane front position, use your right arm to model 2
the chiral center. Match fingers and priority
1 numbers, and turn at elbow to rotate the low 3
priority group away from your viewing
perspective.
1
2
C 4
3
3
2 Turn your right arm around to rotate 4 away
from you. Remember which fingers are
The circle traces 4 assigned 1 and 2 to start the trace of your
clockwise = R circle, clockwise in this example.
absolute configuration.
Chem 201/Beauchamp Topic 7, Stereochemistry 9 Chem 201/Beauchamp Topic 7, Stereochemistry 10

Example 2 Problem 1 - Classify the absolute configuration of all chiral centers as R or S in the molecules below. Use hands
NH2 (or model atoms) to help you see these configurations whenever the low priority group is facing towards you (the
F H2 wrong way). Find the chiral centers, assign the priorities and make your assignments.
*C C I
C
H2 C C a. b. c. d.
CH2 H2 H2 first sphere First sphere of consideration CH3
Cl Cl H H H3C H H
C H3C H
H2 second sphere 1=N Cl Br
C
2=C HO
H H Cannot make a decision C CH3
* = chiral center third sphere 3=C since all atoms are the I
N H3C H
4=C same. H CH3 C
H H H H
*C H3C
H
F C H H
H C fourth sphere Second sphere of consideration e.
C H O f. g. h.
H C
C H C H Br
H H I 2 = (F,H,H) F is higher priority than C or H. Br OH
H 3 = (C,H,H) Cannot decide H H CH3
Cl H
H H 4 = (C,H,H) between these two. C
H3C
CH3 CH3
C H3C H
Third sphere of consideration H H
Cl H3C H
Circle traces CCW = S. 3 = (Cl,H,H) Cl is higher priority
1 4 = (C,H,H) i. j. Cl k. l.
If in doubt, use your right CH2CH3
arm and hand from the side. H3CH2C Br
*C H CH3
2 Fourth sphere of consideration H C Br Cl
4 S
D
3 Already decided, CH3 CH3
4 = (I,H,H) CH3 H
O
not necessary. H
Pi Bond Priority
The temptation in this example is to see the iodine and immediately classify it as the highest priority group.
However, we have to pass through several spheres of priority before we come to the iodine atom and the priority Pi bonds of all kinds are common in organic chemistry. If a double bond is present, it is assumed that each
decision is already decided when we reach it. atom of the double bond is duplicated, and if a triple bond is present it is assumed that each atom of the triple bond
is triplicated. Since real atoms are obvious, this involves drawing in (or thinking) one additional imaginary atom in
Example 3 One additional (and tricky) example will also prove helpful. double bonds or two additional imaginary atoms in triple bonds. The imaginary atoms are sometimes placed inside
F
parentheses, as illustrated below.
first sphere First sphere of consideration Additional attached groups
H2C
second sphere 1=O H H H
*C CH3 2=C Cannot make a decision since C1 (C,C,H)
H H F H third sphere 3=C both atoms are the same.
C H * C CH2 * C1 C2 H
C 4=H
HO H C2 (C,H,H)
CH3
H
H3C *C
H C H * = path to chiral center (C) (C)
C Second sphere of consideration
* = chiral center C Additional attached groups
O
C H
H 2 = (F,H,H) F is higher priority than H H
H 3 = (C,C,C) all of the C atoms.
H 2 C (O,O,H)
H H * C O * C O
O (C, , )
*C
Circle traces CW = R. (O) (C)
4
3 Additional attached groups
1 H H H

In this example the temptation is to consider three carbon atoms higher in priority than one fluorine atom and * C N CH3 C N C H C (N,N,H)
*
two hydrogen atoms. Remember, it is the atom with the highest atomic number that establishes the priority. If all N (C,C, )
attached groups on one atom are equivalent to all attached groups on another atom, you move to the next sphere of H
(N) (C)
consideration. What we need now is some practice. C (H,H,H)
Chem 201/Beauchamp Topic 7, Stereochemistry 11 Chem 201/Beauchamp Topic 7, Stereochemistry 12

(C) (C)
Additional attached groups possible (sometimes it could be less). There may be fewer than this number of stereoisomers, if special symmetry
H
features are present (such as meso structures, discussed later).
* C C CH3 * C1 C2 C3 H
C1 (C,C,C) Maximum number of stereoisomers.
Number of (There may be fewer than this number
H C2 (C,C,C) Stereogenic Centers if meso compounds are present.)
(C) (C) 1 21 = 2
C3 (H,H,H) 2 22 = 4
3 23 = 8
(N) (C)
Additional attached groups 4 24 = 16
etc.
* C N * C N flipping coins
C (N,N,N) absolute configurations
H ...or... T R ...or... S
N (C,C, )
(N) (C) (R,S)
(H,H) (H,T) (T,H) (T,T) (R,R) (S,R) (S,S)
Problem 2 - Evaluate the order of priority in each part from highest (= 1) to lowest (= 4).
a. (H,H,H) (H,H,T) (H,T,H) (H,T,T) (T,H,H) (T,H,T) (T,T,H) (T,T,T) (R,R,R) (R,R,S) (R,S,R) (R,S,S) (S,R,R) (S,R,S) (S,S,R) (S,S,S)
H H
* = path to chiral center
CH3 CH3 2, 4, 8, 16, 32, etcertera possibilities 2, 4, 8, 16, 32, etcertera possibilities
C C
If you look carefully at these 8 possibilities, you will find that
C CH2 * C CH3 there are 4 pairs of enantiomers.
* C C H * C C H *
top top top top
C C CH3 R S S R R S R S
R S R S S R R S
H H R S R S R S S R
ethynyl phenyl 2-propenyl t-butyl bottom bottom bottom bottom
b.
O CH3 Fischer Projections – A useful method for representing stereoisomers with more than one chiral center
H2 H2 H2 H2 H2
* C C C C F C C N C C I
A reasonably simple molecule with multiple chiral centers to consider is 2-bromo-3-chlorobutane. If we first
* * *
draw a 2D structure we can identify any chiral centers. Stereogenic atoms are easy to identify because they have
H four different groups at a tetrahedral center. 2-bromo-3-chlorobutane has two stereogenic atoms, C2 and C3, and are
OH
marked with asterisks, below.
c.
H H CH3 mirror mirror
O H O O Br Cl plane plane
* = chiral center = stereogenic center
* *C R S R S
* C O * C O * C O * C O H3C C CH3 2 chiral centers present
H CH3 CH3 2
2 = 4 possible stereoisomers R S S R
H H H H H
d. enantiomers enantiomers

Br
Any stereogenic center has a 50/50 chance of two possible outcomes, R and S (or E and Z at double bonds). In
* * * *
this example, the possible number of stereoisomers is a maximum of 22 = 4 possible stereoisomers,. There may be
fewer than this number of stereoisomers, if special symmetry features are present (such as meso structures,
discussed soon).
Cl
Fischer projections are a convenient new way to draw stereoisomers having more than one chiral center. These
Any stereogenic center has two possible outcomes, R and S (or E and Z at double bonds). It might occur to drawings will allow us to quickly and easily evaluate if stereoisomers are enantiomers, diastereomers or meso
you that the chance of encountering a specific absolute configuration or its mirror image is the same as getting compounds in comparisons with one another.
heads (H) or tails (T) when flipping a coin (a 50/50 proposition). With only one flip you can get only heads (H) or Fischer projections require that we place the longest carbon chain in the vertical direction. The highest priority
tails (T), but with two flips you have four possible outcomes (H,H), (H,T), (T,H), (T,T) and so forth. This would nomenclature group is placed in the top half of the drawing. Priority in this instance refers to nomenclature
correspond to absolute configurations of (R,R) (R,S) (S,R) or (S,S). A third flip of a coin doubles this number priorities and not the R,S priorities we’ve just been discussing. This is, unfortunately, a confusing use of the word
again to eight. Each time you flip a coin an additional flip or each time there is an additional stereogenic center, the “priority”, but you need to keep the difference straight.
total number of possibilities doubles from the prior number. The result for the possible number of stereoisomers is All along that vertical chain are drawn the other two groups at each sp3 atom in horizontal positions, one to the
a maximum of 2n stereoisomers, where n equals the number of stereogenic atoms. This is a maximum number left and one to the right. The horizontal groups along the longest carbon chain backbone are considered to be
coming out in front of the page, towards you (the viewer). Vertical groups are considered to be projecting back,
Chem 201/Beauchamp Topic 7, Stereochemistry 13 Chem 201/Beauchamp Topic 7, Stereochemistry 14

behind the page (away from you). With these assumptions, wedges and dashed lines may be dropped and simple As a consequence of placing the longest carbon chain in the vertical position, and having the horizontal groups
lines used in their place. The center atom is omitted as well, and merely understood to exist at the crossing point of facing forward, assigning absolute configurations (R/S) will usually require that chiral centers be turned around. If
horizontal and vertical lines. there is a hydrogen atom bonded to a chiral center (usually the case), it will always be in a horizontal position. You
To show how they are created and used, it may prove helpful to first represent a molecule using a familiar will find the hand/arm approach to classify chiral centers as R or S works very well in this situation. It is fast,
Newman projection in an eclipsed conformation (higher potential energy), and then with wedges and dashed lines accurate and easy. If you have a whole series of stereoisomers to assign, you can make the initial assignments on
in a tilted up position. Alternatively, you can represent a molecule in an eclipsed sawhorse or 3D display. We will the first stereoisomer and use those assignments in all of the rest of the stereoisomers. They will either be the same,
use (2S,3S)-2-bromo-3-chlorobutane as an example (there are actually four possibilities for doing this). or they will be opposite.
The example molecule, above, has two chiral centers and therefore has a maximum of 22 = 4 possible
CH3 CH3
H stereoisomers. Without drawing a single structure, we know that the absolute configurations will be (R,R) and its
H * Br
* CS Cl H Cl H CS mirror image (S,S), and (R,S) and its mirror image (S,R). My approach when drawing a complete set of
Br
Cl Br Cl H stereoisomers is to place all of the “different” groups on one side (Br and Cl here). Then, beginning at the top,
H H = = *
C C individually move one group across at a time all the way down the line. For each possible structure, I immediately
* S (twist rear carbon S CH
Br H 3
atom 180o) draw its mirror image and check to see if it is different (probably enantiomers, though if meso, the mirror images
CH3 H3C CH3 CH3
CH3 will be identical). If there are enough substituents, you may have to begin at the top again, and move two
staggered sawhorse Newman Newman eclipsed sawhorse
projection projection projection substituents to the other side, and so forth. You should also check that your later drawn structures do not duplicate
projection
* = chiral center (staggered) (eclipsed) * = chiral center some earlier drawn structures. (This occasionally occurs in symmetrical molecules). You need some sort of
systematic approach to draw all the possibilities. I have used my approach with Fischer projections of 2-bromo-3-
Tilt up towards viewer with horizontal chlorobutane, below.
groups facing forward, in front of the page.
mirror mirror
CH3 CH3 plane plane
The vertical groups project 3D details eliminated * CH3 CH3 CH3 CH3
backwards, behind the page, H * Br H C Br
S as in a normal Fischer S
and the horizontal groups projection. Br H
project forwards, in front * *C H Br Br H H Br
Cl H Cl H
of the page. Carbon atoms S S
lie at the crossing points of H Cl Cl H H Cl Cl H
CH3 CH3
the lines.
3D Fischer projection,
Regular Fischer projection with wedges and dashes CH3 CH3 CH3
CH3
1 2 3 4
Basic Rules For Drawing Fischer Projections Place both Br and Cl on the same Move Br across and leave Cl in place
side and then draw the mirror image. and then draw the mirror image.
1. Place the longest carbon chain in vertical direction, with the highest nomenclature priority group in the top half
The maximum number of stereoisomers is 22 = 4. The horizontal groups, including hydrogen atoms are
of your representation. toward you. To assign the absolute configuration of any chiral centers will require that the low priority
hydrogen atom be turned away to trace the direction of the other priorities, 1 to 2 to 3, as R or S.
2. Horizontal groups will project toward the front (in front of the page/surface).
The assignment of absolute configurations in all of the stereoisomers can be made by specifying the priorities at
3. Vertical groups will project away from the viewer (in back of the page/surface). each chiral center in the first stereoisomer, (1). In this example we would use the left arm and hand to assign both,
since the lowest group, hydrogen, is on the left side in each case. I usually double check myself one time to see if I
4. A carbon atom is indicated at each intersection of vertical and horizontal lines. get the opposite result on the enantiomer (2). If that classification seems correct, I label all of the other absolute
configurations by comparison to the first structure (either they are the same or opposite).
5. As much as possible, place non-hydrogen substituents on the same side in your first structure (I use the right).

6. Immediately draw the mirror image of that structure (groups on the right will move to the left and vice versa).

7. Move the top-most group across to the other side and immediately draw the mirror image.

8. If you can, continue to move single groups across, one at a time, until you reach the maximum number of
stereoisomers based on the number of chiral centers.

9. With four or more chiral centers, you can start again at the first structure and move two substituents at a time
across, and draw the mirror image until you reach the maximum number of stereoisomers. (Four chiral centers
would potentially have 16 stereoisomers.)
Chem 201/Beauchamp Topic 7, Stereochemistry 15 Chem 201/Beauchamp Topic 7, Stereochemistry 16

3 It is important that you remember that the horizontal groups are toward you. You can move any drawing 180o
CH3 CH3 Use your left arm as "4" and
turn it around to trace the
around in the plane of the page and the horizontal groups will still be toward you as long as you do not lift the
circle of 1 to 2 to 3. The structure off of the plane of the page. This is a maneuver you will occasionally have to do when comparing
H C2 Br = H C2 Br = 4 C2 1
absolute configuration of C2 stereoisomers. This is analogous to you being stood on your head, but always facing the same direction. In either
is S. (Use your right arm with position, we could always recognize your face and know that it was you.
chain chain the enantiomer.)
2
Allowable rotations
do not lift the structure
2 Use your left arm as "4" and off of the page.
chain chain CH3
turn it around to trace the CH3
= = circle of 1 to 2 to 3. The
H C3 Cl H C3 Cl 4 C3 1 H Cl These two drawings
absolute configuration of C2 H Br Rotate 180o in
is R. (Use your right arm with look different, but
CH3 CH3 the plane of the are actually the same
3 the enantiomer.) Br H molecule.
Cl H page.
mirror mirror
plane CH3 CH3
plane
CH3 CH3 CH3 CH3
You may NOT turn the molecule over (like flipping pancakes), since that would make the horizontal groups
S R R S The absolute configurations
H Br Br H Br H H Br project away from you, (behind the page). This effectively inverts all stereogenic centers and generates the mirror
of these two were assigned by image structure, as represented by a two dimensional Fischer projection. The mirror image structure may or may
comparing them to the first
H Cl Cl H H Cl Cl H two structures. not be different (an enantiomer or a meso compound) depending on what symmetry features are present.
R S R S
CH3 It is incorrect to lift molecule
CH3 CH3 CH3 CH3 CH3
off the page and flip it over.
1 2 3 4
Backwards horizontal groups are away.
H Br Br H If drawn as a Fischer projection, this
Stereoisomer 1 is part mirror image and partially identical to both 3 and 4. It is neither identical, nor an molecule would appear as its mirror
enantiomer of these molecules. Cl H H Cl image. Everyone looking at it would be
Do not flip molecule fooled.
CH3 mirror image CH3 CH3 CH3 over on the page.
identical CH3 CH3
S configuration S configuration S
R
H Br Br H H Br H Br
Our hands can again provide us with a useful analogy. Specifying that horizontal groups are toward us is
H Cl H Cl
similar to always specifying the back of the hand as always facing up in a drawing (finger nails up). With this
H Cl Cl H
R identical R R mirror image S convention we could view a trace of the hand and always know for sure if it was a left or right hand. However, if
configuration configuration you drew your hand, palm up, anyone looking at your drawing would be completely confused about what you were
CH3 CH3 CH3 CH3
1 3 1 4 trying to represent. Fischer projections are similar.
diastereomers diastereomers

These relationships are grouped in the class of diastereomers. Stereoisomer 2 is likewise a diastereomer of both
structures 3 and 4. There are two pairs of enantiomers (1,2) and (3,4) and four pairs of diastereomers (1,3), (1,4),
(2,3) and (2,4).
It is easy to include chiral centers as part of a name. You can use the same chemical name for all of the We can't tell top or This must be a right Our convention tells us
bottom without hand, if the convention this is a left hand, but the
stereoisomers, without consideration of stereochemistry, and just put the number and its absolute configuration (R some convention? added features reveal it is
tells us we are always
or S) of each stereocenter in parentheses in front of the name. looking at the top of a right hand drawn in
mirror mirror a hand. violation of convention.
plane plane
CH3
CH3 CH3 CH3
S
H Br R R S
Br H Br H H Br
H Cl
R Cl H H Cl Cl H
S R S
CH3
CH3 CH3 CH3

(2S,3R)-2-bromo-3-chlorobutane (2R,3S)-2-bromo-3-chlorobutane (2R,3R)-2-bromo-3-chlorobutane (2S,3S)-2-bromo-3-chlorobutane

Chem 201/Beauchamp Topic 7, Stereochemistry 17 Chem 201/Beauchamp Topic 7, Stereochemistry 18

Meso Structures CH3

CH3 CH3 CH3
Let's now look at all possible 2,3-dibromobutanes.
H Br Br H Br H H Br
mirror mirror
Br Br plane plane H Br Br H H Br Br H
* = chiral center = stereogenic center
* *C R S R S
H3C C CH3 2 chiral centers present CH3 CH3 CH3 CH3
mirror
22 = maximum of 4 possible stereoisomers R S S R plane
mirror
H H 5 6 7 plane 8
enantiomers enantiomers
Rotate 5 180o in o
Rotate 7 180 in the
the plane of the page. identical different
We will follow the same systematic approach used with the 2-bromo-3-chlorobutane isomers (above), plane of the page.
mirror mirror CH3 CH3
plane plane Rotated 5 looks identical Rotated 7 does NOT look
CH3 CH3 CH3 CH3 Br H to its mirror image, 6. Br H identical to its mirror image, 8.
These two structures are 7 looks the same as before it was
H Br Br H Br superimposable. rotated. These two structures (7
Br H H Br H H Br
and 8) are not superimposable,
and therefore are enantiomers.
H Br Br H H Br Br H CH3 CH3

CH3 CH3 CH3 CH3 Structures such as 5/6, which have stereogenic centers but are achiral as molecules, have a special name. They
5 6 7 8 are called "meso" structures (Greek = middle). The name meso (middle) provides us with an explanation for the
Place both Br's on the same side Move Br across and leave the bottom Br lack of chirality. If we cut the molecule 6a in two pieces, horizontally, right in the middle (meso), we discover that
and then draw the mirror image. in place and then draw the mirror image. the top half is a reflection of the bottom half. The top half also reflects across to its mirror image, structure, 6.
Since these are both mirror image representations of the same stereogenic atom, they must be identical. In a similar
The maximum number of stereoisomers is 22 = 4. The horizontal groups, including hydrogen atoms are way, the same is true for the bottom carbon atom. This is the principle advantage of Fischer projections. You
toward you. To assign the absolute configuration of any chiral centers will require that the low priority can do this bisection in an instant, comparing the top half of the molecule to the bottom half. If they are mirror
hydrogen atom be turned away to trace the direction of the other priorities, 1 to 2 to 3, as R or S. images of one another, then the molecule is meso, and identical to its mirror image.
As before, we want to be systematic in our approach, so we draw the Fischer projection with both substituents
CH3 CH3 The bottom chiral center in 5 and the top chiral
on one side and then move the top bromine over to the other side. In each case we immediately generate the mirror center in 6 are both mirror reflections of the same
image structure and see if it is different. You should also check that later drawn structures do not duplicate some chiral center (top in 5). They must, therefore,be
earlier drawn structures, which occasionally occurs in symmetrical molecules that are larger than this example. mirror H Br Br H
identical. The same is true in the reverse direction.
We don’t expect more than 22 = 4 stereoisomers and can stop after drawing the four stereoisomers shown plane? The top chiral center in 5 and the botton chiral center
(yes!) H Br Br H in 6 are both mirror reflections of the same chiral
above. This is a maximum number possible, not a required number.
center (bottom in 5) and must, therefore, be identical.
We can rotate structure 5 180o in the plane of the page (do not flip it over) to compare it to its mirror image, 6. Because of the mirror plane bisecting 5, it is a meso
CH3 CH3
When we do this, we discover something that we have not seen before in a molecule that has chiral centers. We structure and identical to its mirror image, even though
mirror
find that the mirror images (5/6) are identical (superimposable), which means that the two structures are NOT 5 plane 6 chiral centers are present.
enantiomers. Instead, they are identical. In a similar way, we can compare 7 and 8. This mirror image pair (7/8) is
not superimposable (i.e. – they are enantiomers). Even though four stereoisomers can be drawn, only three are In the other pair of stereoisomers (7 and 8), there is no mirror plane dividing the two halves. The three groups
actually different structures (5 = 6 and 7  8). on the top half do not eclipse the same three groups on the bottom half. These two structures are different and
enantiomers.
CH3 CH3
The bottom chiral center in 7 and
mirror Br H H Br the top chiral center in 8 are not
plane? identical. These two molecules are
(No!) H Br Br H different mirror images. They are
enantiomers.
CH3 mirror CH3
7 plane 8

Molecules 5 (= 6, meso) and 7 or 8 are also stereoisomers (same connectivity but different orientations in
space). However, 5 is not the mirror image of 7 or 8. If we compare 5 to 7 we find that the top stereogenic atom is
Chem 201/Beauchamp Topic 7, Stereochemistry 19 Chem 201/Beauchamp Topic 7, Stereochemistry 20

a mirror image and the bottom stereogenic atom is identical. These stereoisomers are diastereomers. This type of Problem 3 – For the following set of Fischer projections answer each of the questions below by circling the
stereoisomerism is observed when two molecules have the same overall connectivity of atoms, yet are neither appropriate letter(s) or letter combination(s). Hint: Redraw the Fischer projections with the longest carbon chain in
enantiomers nor identical. the vertical direction and having similar atoms in the top and bottom portion (highest nomenclature priority in the
top half). Classify all chiral centers in the first structure as R or S absolute configuration. (15 pts)
CH3 mirror image CH3
configuration CH3 CH3 OH NH2 CH3
H Br Br H
H OH H OH H CH3 H CH3 H OH
H Br H Br
identical H2N H H3C H H CH3 H OH H2N CH3
configuration
CH3 CH3 CH3 OH CH3 H
NH2
5 = 6 = meso diastereomers 7
A B C D E
A similar result is observed with 5 and 8.
a. Which are optically active? A B C D E
CH3 identical CH3
b. Which are meso? A B C D E
configuration
H Br H Br c. Which is not an isomer with the others? A B C D E
d. Which pairs are enantiomers? AB AC AD AE BC BD BE CD CE DE
H Br Br H e. Which pairs are identical? AB AC AD AE BC BD BE CD CE DE
mirror image
configuration f. Which pairs are diastereomers? AB AC AD AE BC BD BE CD CE DE
CH3 CH3
5 = 6 = meso diastereomers 8 g. Which pairs, when mixed in equal amounts AB AC AD AE BC BD BE CD CE DE
will not rotate plane polarized light?

Instead of the maximum four stereoisomers, we only find three, because of the meso structure. Structures 5 and h. Draw any stereoisomers of 3-amino-2-butanol as Fischer projections, which are not shown above.
If there are none, indicate this.
6 are identical (meso) and diastereomeric with 7 and 8, which are enantiomers. Naming the structures is easy,
because we only change the R and S descriptors in the front of the name. i. Would anything change if, in compound C, the NH2 was replaced with a OH group?
j. Circle all chiral centers in a recently discovered Costa Rican fungal compound showing antibacterial
CH3 CH3 properties against vancomycin resistant bacteria. How many stereoisomers are possible with that many
CH3 chiral centers?
S R S H3C
H Br Br H H Br
O
R R S O
H Br H Br Br H O
H
CH3 CH3 CH3
5 = 6 = meso 7 8
(2S,3R)-2,3-dibromobutane (2R,3R)-2,3-dibromobutane (2S,3S)-2,3-dibromobutane H3C H guanacastepene A

Diastereomers usually have different physical properties. Unlike enantiomers, which are completely identical Problem 4 - Place glyceraldehyde (2,3-dihydroxypropanal) in the proper orientation to generate a Fischer
in the absence of a chiral environment, diastereomers will have different melting points, boiling points, solubilities, projection. Can you find any stereogenic centers? Is the molecule as a whole chiral? If so, draw each enantiomer
spectra and the like (except by coincidence). Recall that a 50/50 racemic mixture of enantiomers is yet another as a 3D representation and classify all stereogenic centers as R or S.
common arrangement or stereoisomers. Racemic mixtures usually have different physical properties from the other
stereoisomer possibilities, as well. Problem 5 - Draw a 3D Newman projection and a sawhorse representation for each the following Fischer
projections. Redraw each structure in a sawhorse projection of a stable conformation. Identify stereogenic atoms
as R or S.
a. b. c.
CH3 NH2 F d.
OH

HO H H3C H Cl Br H3C H

H H H CH3 H H H3C H

CH3 D CH3 OH
Chem 201/Beauchamp Topic 7, Stereochemistry 21 Chem 201/Beauchamp Topic 7, Stereochemistry 22

Remember: The absolute configurations, R and S, are defined by an arbitrary system of priorities to allow Six carbon aldose carbohydrates – 16 possible, all are 2,3,4,5,6-pentahydroxyhexanal
everyone to draw or think about actual 3D structures for comparisons. They apply to a single chiral center. Optical O O O O O O O O
H H H H H H H H
rotations, (d,l) = (+/-), on the other hand are experimental values determined by observing the rotation of plane C C C C C C C C
polarized light of the entire molecule (right = d = dextrorotatory and left = l = levorotatory). Molecules having one R
or multiple chiral centers (1, 10s, 100s…) as R and/or S have only a single value for d or l. H OH HO H HO H H OH H OH HO H H OH HO H
R
H OH HO H H OH HO H HO H H OH H OH HO H
Biological examples of chiral molecules – the aldose sugars
R
H OH HO H H OH HO H H OH HO H HO H H OH
Some of the following carbohydrates show a small sampling of Nature’s choices for energy use, structural R
support and also serve as recognition targets in cells. Nature almost exclusively picks one enantiomer of a pair. H OH HO H H OH HO H H OH HO H H OH HO H
When drawn as a Fischer projection it is the stereoisomer having the second to the last OH on the right side. In CH2OH CH2OH CH2OH CH2OH CH2OH CH2OH CH2OH CH2OH
Biochemistry, this is referred to as the “D” isomer. If the second to last OH were on the left side in a Fischer D-allose L-allose D-altrose L-altrose D-glucose L-glucose D-gluose L-gluose
projection it would be referred to as the “L” isomer. These are different from d and l of optical rotations. There is
no logical reason for these designations. They must be memorized, as do the positions of all of the other “OH”
O O O O O O O O
groups up the chain. “Reducing carbohydrates” have an aldehyde carbon at C1 and can be 2Cs, 3Cs, 4Cs, 5Cs, 6Cs H H H H H H H H
C C C C C C C C
or more in length. Glucose is probably the most famous of the carbohydrates. Some of these are shown below.
How many chiral centers does each example have? How many stereoisomers are possible for each length of HO H H OH H OH HO H HO H H OH HO H H OH
carbon? What are the absolute configurations of any chiral centers? What stereochemical relationship does the
HO H H OH HO H H OH H OH HO H HO H H OH
first stereoisomer as A (then B, C, etc.) have to the others? Are there any meso structures.
H OH HO H HO H H OH HO H H OH HO H H OH
Three carbon aldose carbohydrates – two possible, all are 2,3-dihydroxypropanal
H OH HO H H OH HO H H OH HO H H OH HO H
O O
H H D L
R When the second to the last "OH" is on the CO2H CH2OH CH2OH CH2OH CH2OH CH2OH CH2OH CH2OH
C C CH2OH
right side, biochemists refer to it as a "D" D-mannose L-mannose D-galactose L-galactose
R D-idose L-idose D-talose L-talose
H OH carbohydrate. Most carbohydrates in nature H2N H
H OH HO H are "D". Most amino acids, on the other
CH2OH hand are "L" with a "NH2" on the left side. R Problem 6 – What would happen to the number of stereoisomers in each case above if the top aldehyde
CH2OH CH2OH
D-glyceraldehyde L-glyceraldehyde
generic carbohydrate generic amino acid functionality were reduced to an alcohol functionality (a whole other set of carbohydrates!)? A generic structure is
provided below to show the transformation. Nature makes some of these too. How many chiral centers does each
Four carbon aldose carbohydrates– four possible, all are 2,3,4-trihydroxybutanal example have? How many stereoisomers are possible for each length of carbon? What are the absolute
configurations of any chiral centers? Specify the first stereoisomer as A (then B, C, etc.) and state what each
O O O O relationship is to the others. Are there any meso structures.
H H H H
C C C C Biochem names are all different. Organic names are easier.
All of these are 2,3,4-trihydroxybutanal.
R
H OH HO H HO H H OH
1 = (2R,3R)-2,3,4-trihydroxybutanal
R 2 = (2S,3S)-2,3,4-trihydroxybutanal
H OH HO H H OH HO H
3 = (2S,3R)-2,3,4-trihydroxybutanal
CH2OH CH2OH CH2OH CH2OH 4 = (2R,3S)-2,3,4-trihydroxybutanal
D-erythrose L-erythrose D-threose L-threose Three carbon tri-ol carbohydrate = becomes only one structure which is achiral
Four carbon tetra-ol carbohydrates = becomes three stereoisomers (one meso pattern)
Five carbon aldose carbohydrates – eight possible, all are 2,3,4,5-tetrahydroxypentanal Five carbon penta-ol carbohydrates = becomes four stereoisomers (two meso patterns, one duplication)
Six carbon hexa-ol carbohydrates = becomes ten stereoisomers (two meso patterns, two duplications)
O O O O O O O O
H H H H H H H H
C C C C C C C C Problem 7 – How many chiral centers are found in cholesterol? How many potential stereoisomers are possible?
R Nature only makes one of them!
H OH HO H HO H H OH H OH HO H HO H H OH H
R
H OH HO H H OH HO H HO H H OH HO H H OH CH3
R H
H OH HO H H OH HO H H OH HO H H OH HO H
CH3 H
CH2OH CH2OH CH2OH CH2OH CH2OH CH2OH CH2OH CH2OH
D-ribose L-ribose D-arabinose L-arabinose D-xylose L-xylose D-lyxose L-lyxose
H H

HO
cholesterol
Chem 201/Beauchamp Topic 7, Stereochemistry 23 Chem 201/Beauchamp Topic 7, Stereochemistry 24

Topic 7 Possible answers to problems

4 1 2 3
Problem 1 (p 11) - Classify the absolute configuration of all chiral centers as R or S in the molecules below. Use d
hands (or model atoms) to help you see these configurations whenever the low priority group is facing towards you * * * * Br

(the wrong way). Find the chiral centers, assign the priorities and make your assignments.
a. b. 3 c. d. no chiral centers C1(CCC) C1(CCC) C1(CCC) Cl C1(CCC)
1 4 4
Cl H H H3C H CH3 C2(CCH) C2(CCC) C2(CCH) C2(CCH)
H3C H
H C3(CCH) C3(CCH)
Cl Br C3(CCH) C3(C,C,Cl)
HO R C C4(CCH)
1 2 C4(CCBr)
R S S C CH3
2 I H
3 CH3 H3C
H C Problem 3 (p 24) – For the following set of Fischer projections answer each of the questions below by circling the
H H H H3C H appropriate letter(s) or letter combination(s). Hint: Redraw the Fischer projections with the longest carbon chain in
e. the vertical direction and having similar atoms in the top and bottom portion. Classify all chiral centers in the first
O f. g. h.
no chiral centers structure as R or S absolute configuration. (15 pts)
H Br
Br OH
H CH3 CH3 CH3 NH2 NH2
S H H CH3
C
H3C R S H NH2 H OH H3C H H CH3 H OH
CH3 CH3
C H3C H
H R H HO H H3C H H3C H H OH H2N CH3
H3C H
Cl
CH3 OH OH CH3
i. Cl H
j. k. l.
CH2CH3 S H3CH2C Br D
A B C E
H CH3
CH3 CH3
H C Br Cl R CH3 CH3
R S
R D
CH3
Structures are H2N H H2N H
CH3 H CH3 redrawn in a H OH H NH2
H O S
similar Fischer H OH
projection format. H OH H OH HO H
Problem 2 (p 12) - Evaluate the order of priority in each part from highest (= 1) to lowest (= 4). CH3
CH3 CH3 CH3
H H
a * = path to chiral center
1 3 CH3 4 CH3
2 C C a. Which are optically active? A B C D E Eliminate these because
C CH3
B is not an isomer.
C C H * C C H * C CH2 * b. Which are meso? A B C D E
*
c. Which is not an isomer with the others? A B C D E
C1(CCC) C1(CCC) C C CH3
C1(CCC) d. Which pairs are enantiomers? AB AC AD AE BC BD BE CD CE DE
C2(CCH) C2(CCH) H H
C1(CCC)
C3(none) ethynyl phenyl C2(CHH) C2(HHH) t-butyl e. Which pairs are identical? AB AC AD AE BC BD BE CD CE DE
C3(CCH) 2-propenyl
C3(none) C3(none) f . Which pairs are diastereomers? AB AC AD AE BC BD BE CD CE DE
g. Which pairs, when mixed in equal amounts AB AC AD AE BC BD BE CD CE DE
b 3 O 2 4 CH3 will not rotate plane polarized light?
1
H2 H2 H2 H2 H2 h. Draw any stereoisomers of 3-amino-2-butanol as Fischer projections, which are not shown above.
* C C C C F C C N C I If there are none, indicate this. All are shown.
* * * C
i. Would anything change if , in compound C, the NH2 was replaced with a OH group? It would be like B.
C1(CHH) H C1(CHH) C1(CHH) C1(OCC)
C2(OOH) C2(FHH) OH j. Circle all chiral centers in a recently discovered Costa Rican fungal compound showing antibacterial
C2(NNN) C2(I HH) properties against vancomycin resistant bacteria. How many stereoisomers are possible with that many
chiral centers? enantiomers
HC meso
H H CH3 3
c 3 H 2 1 CH3 CH3 CH3
4 O O O O
O 4
C O * C O C O C O O 2 = 16 possible H OH HO H H OH
* * * H * stereoisomers
H C1(OOH) CH3 CH3 H OH H OH HO H
H C1(OOH) H C1(OOH) H *
C1(OOH) O2(C)
O2(H) O2(C) (twice) *
O2(C) C3(HHH) * CH3 CH3 CH3
C3(HHH)
H3C H guanacastepene A B B B
Chem 201/Beauchamp Topic 7, Stereochemistry 25 Chem 201/Beauchamp Topic 7, Stereochemistry 26

Problem 4 (p 25) - Place glyceraldehyde (2,3-dihydroxypropanal) in the proper orientation to generate a Fischer Problem 6 (p 28) – What would happen to the number of stereoisomers in each case above if the top aldehyde
projection. Can you find any stereogenic centers? Is the molecule as a whole chiral? If so, draw each enantiomer functionality were reduced to an alcohol functionality (a whole other set of carbohydrates!)? A generic structure is
as a 3D representation and classify all stereogenic centers as R or S. provided below to show the transformation. Nature makes some of these too. How many chiral centers does each
O O H O example have? How many stereoisomers are possible for each length of carbon? What are the absolute
O H
H2 H2 C C configurations of any chiral centers? Specify the first stereoisomer as A (then B, C, etc.) and state what each
C * C C C relationship is to the others. Are there any meso structures.
*
HO C H HO C H H OH
HO H
HO H OH
H CH2 H 2C
2S 2R HO OH

There is only 1 chiral center, so the molecules are chiral and enantiomers. 2S 2R
3 carbons 4 carbons 5 carbons
OH OH OH HO
Problem 5 (p 25) - Draw a 3D Newman projection and a sawhorse representation for each the following Fischer OH OH HO
OH H2C H2C H2C CH2
H2C H2C CH2
projections. Redraw each structure in a sawhorse projection of a stable conformation. Identify stereogenic atoms H2C
R R
R H OH H OH HO H H OH
as R or S. H OH
H OH HO H H OH
a. R R
R H OH HO H H OH HO H
CH3 H OH H OH HO H
CH3 H3 C H2C R
2R H HO H OH H
R
OH H OH H OH HO H
HO H H2C H2C CH2
HO H H H glycerol OH OH HO
H H H2C H2C H2C CH2
H OH achiral meso enantiomers
H H OH OH OH HO
H H CH3 H meso 2
butan-1,2,3,4-tetraol meso 1 enantiomers
OH pentan-1,2,3,4,5-pentaol
H3C H
CH3 H3C CH3 CH3 CH3 OH OH OH HO OH HO OH HO OH HO
H 2C H2C H2C CH2 H2C CH2 H2C CH2 H2C CH2
Fischer Newman sawhorse sawhorse R
H OH H OH HO H H OH H OH HO H HO H H OH HO H H OH
projection projection eclipsed staggered R
H OH HO H H OH HO H HO H H OH HO H H OH H OH HO H
R
H OH HO H H OH HO H H OH HO H H OH HO H HO H H OH
R
H OH H OH H OH HO H H OH HO H H OH HO H H OH HO H

H 2C H2C H2C CH2 H2C CH2 H2C CH2 H2C CH2

OH OH OH OH HO OH OH
HO HO HO
meso 1 meso 2 enantiomers enantiomers enantiomers enantiomers

Three carbon tri-ol carbohydrate = becomes only one structure which is achiral

F F Four carbon tetra-ol carbohydrates = becomes three stereoisomers (one meso pattern)
H
c. Cl Cl Br
F Br H H
H Five carbon penta-ol carbohydrates = becomes four stereoisomers (two meso patterns, one duplication)
2R H H
Br Cl
Cl Br H H
F Six carbon hexa-ol carbohydrates = becomes ten stereoisomers (two meso patterns, two duplications)
Br Cl
H H H3C
F CH3 CH3
CH3 Problem 7(p 28) – How many chiral centers are found in cholesterol? How many potential stereoisomers are
CH3 Newman sawhorse sawhorse possible? Nature only makes one of them!
projection eclipsed staggered
CH3 H3C
d. H3C
OH H3C H3C H
H
H H OH
2S HO
H3C H H3C H H
H OH
OH
3R H
H3C H HO HO
HO OH CH3 CH3
OH Newman sawhorse sawhorse
meso projection eclipsed staggered