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Chirality
Any object is chiral if the mirror image of the object in “non-superimposable” – that is, if you reflect an
object through a mirror, that reflection is not identical to the original object
...

Other examples:

Chirality in shells
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Image
modified from Grande, C
...
H
...
If a molecule has a non-identical mirror image, the molecule
is chiral
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Examples:
Chiral Molecules

CF3
C
H
Cl
Br

CF3
C
Cl
H
Br

O
H 3C

Achiral Molecules

O
OH

NH2

CH3

HO

NH2

CH3

CF3
C
H
Cl
H

CH3

HO

CF3
C
Cl
H
H

OH

Examples of chiral (left) and achiral (right) molecules
...
A mirror plane means that two halves of a molecule are symmetrical; if you can find a way to
duplicate half of a molecule to generate the other half, you’ve found a mirror plane
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As shown in the table above, cis-1,3 dimethylcyclohexane is achiral – its mirror
image is superimposable
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Split the ring in half
along these two carbons
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Consider the following objects
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A

B

D
C
a
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Locate it!
b
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c
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Where is the second, less
obvious mirror plane?
d
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Is object D chiral? If not, draw the
internal mirror plane
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Any sp3 atom with four different groups bound to it is a chiral center
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B is the mirror image of A
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Second period atoms with three bonded groups and a lone pair (i
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amines)
are not chiral, except under extraordinary circumstances
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In the third example on the top row
below, the hydrogen is omitted from the chiral center
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O

CF3
∗
C
H
Cl
Br

∗

H3C

∗

OH

NH2

H Br

CH3
∗

∗

∗

∗

HO

∗

∗

A menagerie of molecules with chiral centers
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Hydrogens may not be explicitly shown
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A molecule can be achiral, but still have chiral centers
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2
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O
Br

HO

O

Br

OH

OH
N

+

a
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(There are 6 of them)
b
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For each circled structure, clearly indicate the
location of the internal mirror plane
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One (and only one) of the achiral compounds from part b is meso
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Assigning Priority
The convention to indicate chirality in the name of a molecule is to use the terms R and S
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F
F
F
O ( R) C
C
C
F
H
F Cl H

F
F

F
C

( S)

O
F
C
C
H
H Cl F

To assign a chiral center, you must assign the groups bonded to the chiral center priority
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The heaviest atom gets the
highest priority, and the lightest atom gets lowest priority
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In Isoflurane, the atoms are H, C, O, and Cl
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The other atoms are assigned priority in
decreasing order
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2
...

4
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Assign priority at the first point of difference
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If you cannot distinguish between groups one bond away, keep stepping through bonds until a difference
is reached
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3
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a
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R-CH3

R-CONH2
(amide)

R-CHO
(aldehyde)

R-COOH

c
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Dealing with multiple bonds
When multiple bonds are around the chiral center, we need to modify our rules slightly
...
In effect, this duplicates atoms in single
bonds, and triplicates atoms in triple bonds
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Four molecules with chiral centers are shown below, with the priority already assigned
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3
CF 3
∗
4 H C Cl
Br 2
1

5
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The chiral centers have
NOT been indicated in this case
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If the lowest priority group is in the back (H, in this case),
draw a curve connecting groups 1, 2, and 3, in that order
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If it rotates counterclockwise, it is S
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Point your right thumb in the
direction of the lowest priority group, and your fingers towards priority group 1 or 2
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This technique is more
versatile because you don’t have to redraw the structure rotated with the low priority group in the back
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The CF3 group rotates to take
the former place of the H
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HF2C

(S)

Counterclockwise = S!

Move the lowest priority
group to the back FIRST!
H moves to the Cl position
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2
O

Escitalopram (Lexapro, Cipralex, Seroplex) is an antidepressant classified as a selective serotonin
reuptake inhibitor
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Assign the absolute configuration of the stereocenter in escitalopram
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“Stereoisomer” is a broad term, and includes cyclohexane chair conformers, cis/trans
double bond substitution, and molecules with identical chirality
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For two molecules to be
enantiomers, all the chiral centers have to be reversed
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7
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Consider structure A (boxed)
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8
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Fifteen of these
diastereomers are shown below
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Without assigning absolute configuration, verify that structures in the
same boxes are enantiomers
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Below is the structure of a lead compound that was key in the development of Ritonavair
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The “core” of the lead compound that was retained in the final drug has
been bolded
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Assign each stereocenter in this lead compound (it is redrawn below) as R or S
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Is this a meso compound? If so, clearly indicate the internal mirror plane
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The most stable chair conformers of both
molecules (along with their mirror images) are shown below
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The mirror
image of the cis-1,2-dibromocyclohexane chair is non-superimposible (build models!)
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Br
H
H

Br
Br

H

Br
H

Br

Br
H

H

10
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Identify each conformer as
chiral or achiral
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This requires a little more work than drawing a Newman projection of an achiral
molecule
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Knowing this enables us to construct a correct Newman projection for chiral molecules
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Start by filling in the
implicit hydrogens
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In this case,
they are the -NHCH3 group and the phenyl group
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In effect, this is like picking up your paper from the right side, and looking at it edge-on
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Conversely, the phenyl group is bound to the
rear carbon (blue), and is facing down
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Now, this can be filled
in on the Newman projection
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This means that the wedge-bond groups can be put on the left side of the Newman
projection, and the dashed-bond groups can be put on the right
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Try rotating the Newman projection to one of the eclipsed conformers, and go backwards (from the
projection to the skeletal structure)
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(+)-Pseudoephedrine is found naturally in Ma Huang, a common Chinese herbal medicine, and as
the active ingredient in cold medications such as Sudafed
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(Ar = aromatic ring, Me = methyl group)

H
OH

H

Me

Ar

HN
H
MeHN

OH

Ar

NHMe

H

OH

MeHN

Ar

HO

Me

Me

H

Ar

H

OH

H
Me

H
NHMe

13
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Draw the
most stable conformers of (+)-pseudoephedrine and (+)-ephedrine
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Would you expect the most stable conformer of (-)-pseudoepehdrine to have a different energy
than that of (+)-pseudoephedrine? Justify your choice with Newman projections

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