5.

1 Do these two drawing represent the

same or different molecules?
CH3 CH3

C C
H H
OH HO
O
H H

T i 5
Topic
A. They are the same.
Stereochemistry
B. They are different.
C I cannot determine
C. determine.

http://courseweb.pitt.edu Stereochemistry

5.2 Do these two drawing represent the As a way of introduction as to why

same or different molecules?
stereochemistry
h is important, lets
l
A. Theyy are the same.
m consider the story of …
B. They are different.
C. I cannot determine.

CH3 CH3

C C
H H
CH3CH2 OH HO
CH2CH3

Stereochemistry Stereochemistry
Thalidomide Benign (S)-Thalidomide ?
The (S)-enantiomer
apparently has medicinal
benefits including:

• prevent morning sickness

• sedative

Stereochemistry Stereochemistry

Teratogenic (R)-Thalidomide Thalidomide Children

The (R)-enantiomer was
linked to severe birth
defects.

Shortened limbs are a teratogenic effect

correlated with pregnant women ingesting
thalidomide within their first trimester.
Thalidomide was never
approvedd for
f medical
di l use
Stereochemistry in the United States Stereochemistry
Why not use only the (S) isomer? New Uses

When a (S) stereo pure

sample of thalidomide is • Approved in 1998 by the
administered,
adm n stered, a racemic
racem c FDA f
FD forr L
Leprosy
pr y (r
(right)
g )
mixture of both
enantiomers are found in • Also used for:
the
h bl
blood.
d  multiple myeloma (bone
marrow cancer)
 Cachexia (weight loss
WHY? and metabolic wasting)
for advanced AIDS
patients

Stereochemistry Stereochemistry

References An infinite number of other

molecules
l l couldld be used
d to
•
•
http://more.abcnews.go.com/sections/living/thalidbkgd/index.html
p g g g
http://www.cnn.com/HEALTH/9709/04/nfm.thalidomide/index.html
introduce the topic,
topic including …
• http://www.fda.gov/cder/news/thalidomide.htm
• http //www.encyclopedia.com/html/t1/thalidom.asp
http://www.encyclopedia.com/html/t1/thalidom.asp
• http://www.ama-assn.org/special/hiv/newsline/briefing/thalido.htm
• http://www-
nt.who.int/tropical
p _diseases/databases/imagelib.pl?imageid=9307154
m g p m g
• http://www.chm.bris.ac.uk/motm/thalidomide/optical2iso.html

Stereochemistry Stereochemistry
 Biological Implications: Carvone Next two slides are the ‘take-home
algorithims’,
l ithi ’ b butt we’ll
’ll focus
f on
understanding rather than recipes.
recipes
Nonetheless, you might find them
helpful as you work the first few
problems but please wean yourself
problems,
of them …
One carvone stereoisomer interacts in the body to produce a
spearmint smell, while the other produces the scent of caraway
seeds.
seeds

Which of the above enantiomers is

speramint (R), and which is caraway (S)?
Stereochemistry Stereochemistry

Stereoisomers Summarized Given two

Do the
molecules
have the same NO The molecules
molecular are not isomers.
formula?

Isomers molecules,
l l how
h do
d YES

Have the same molecular formula,

but different structures. you define their Do the
molecules
have the same NO
The molecules
are structural

relationship?
atomic isomers.
connectivity?

YES

Constitutional isomers Stereoisomers Are the

molecules
different?
NO The molecules
are identical.

Differ
ff in the
h order
d off Atoms are connectedd in the
h same order,
d
attachment of atoms but differ in spatial orientation. YES

Are the
molecules NO The molecules
mirror images? are diastereomers.

E
Enantiomers
ti Di t
Diastereomers YES

Image and non-superimposable Stereoisomers that are not

mirror image
g related as image
g and mirror The molecules

image
are enantiomers.

Stereochemistry Stereochemistry
5.1 Do these two drawing represent the same or
Stereochemistry (Chirality)
different molecules?
= the structural and chemical consequences of the
CH3 CH3 g
arrangements of atoms in space.
p
CH3CH2OH (EtOH)
H
C C
H
Image and mirror
H
OH HO
H image are the same
CH3 CH3 CH3

C C C
H H H
They are the same. H
OH HO
H H
OH

Th are different.
They diff t Rotate by 180o
about C-C bond The SAME as
I cannot determine. External the or
original.
g nal.
mirror
Stereochemistry Stereochemistry plane EtOH (IDENTICAL)
is not chiral.

5.2 Do these two drawing represent the same or

Stereochemistry (Chirality)
different molecules? OH
CH3CH2CH(OH)CH3
Theyy are the same.
m CH3CH2 CH CH3

They are different.

I cannot determine.
CH3 CH3 CH3

CH3
C C C
CH3 H H CH3CH2
OH HO OH
CH3CH2 CH2CH3 H
C C Rotate by 180o
H H about C-C bond
OH HO
CH3CH2 CH2CH3 External
mirror
Stereochemistry Stereochemistry plane
Stereochemistry (Chirality) Stereochemistry (Chirality)
OH OH

CH3CH2 CH CH3 CH3CH2 CH CH3

CH3 CH3 CH3 CH3

H
C C H
C C
CH3CH2 CH3CH2
OH OH OH OH
CH3CH2 H CH3CH2 H

Stereochemistry Stereochemistry

Stereochemistry (Chirality) Stereochemistry (Chirality)

OH OH

CH3CH2 CH CH3 CH3CH2 CH CH3

CH3 CH3 CH3 CH3

H
C C H
C C
CH3CH2 CH3CH2
OH OH OH OH
CH3CH2 H CH3CH2 H

Stereochemistry Stereochemistry
Stereochemistry (Chirality) Stereochemistry (Chirality)
OH OH

CH3CH2 CH CH3 CH3CH2 CH CH3

CH3 CH3 CH3 CH3

H
C C H
C C
CH CH CH3CH2
OH 3 2 OH OH OH
CH3CH2 H CH3CH2 H

Stereochemistry Stereochemistry

Stereochemistry (Chirality) Stereochemistry (Chirality)

OH OH

CH3CH2 CH CH3 CH3CH2 CH CH3

CH3 CH3 CH3

C
H CH3CH2
C H2
C
CH3CH
OH OH OH
CH3CH2 H H2
CH3CH

Stereochemistry Stereochemistry
Stereochemistry (Chirality) The two butanols are:
OH
CH3CH2CH(OH)CH3
Non-superimposable
N s p imp s bl mirror
mi images.
im s
CH3CH2 CH CH3

Image and mirror image Different molecules.

are NOT the same E
Enantiomers.
ti m s
CH3 CH3 CH3

Enantiomers = molecules that are non-

H
C C
H CH3CH2
C superimposable mirror images.
images
OH HO OH
CH3CH2 CH2CH3 H
Rotate by 180o Ethanol does not have an enantiomer.
enantiomer
about C-C bond Different.
External Not superimposable
mirror on the
h orignal,
l
Stereochemistry plane Stereochemistry

“Handed” 2-D vs. 3-D Representation

p

H HCl Cl
H
O Cl

H Cl
OH Cl ClH

OH Cl

The word “chiral” is greek and means ”handed.”

Stereochemistry Stereochemistry
S-Glyceraldehyde R-Glyceraldehyde
 V&S, 5th Ed
Chirality a general property of handedness Plane of Symmetry Explored Figure 5-4

An object, non-superimposable on its mirror image

is chiral
Achiral – molecules
(objects) that are not
chiral.
Obs: Chiral objects lack a
plane of symmetry. C* stereocenter, asymmetric center, asymmetric
A structure
t t with
ith a plane
l of
f carbon,
b chiral
hi l center, chiral
hi l carbon.
b
symmetry is achiral and Molecules containing stereogenic centers may be
mustt b
be identical
id ti l with
ith it
its chiral.
hi l
mirror image. If a molecule contains only one chiral center, the
molecule
l l must be
b chiral.
hi l
Stereochemistry Stereochemistry

Properties
p of Enantiomers
Physical properties of enantiomers are almost
identical, except for their optical activity.
Asside
e

Stereochemistry Stereochemistry
Lets introduce another drawing Fischer Projections - introduced
convention….
convention CH3 CH3
CH3

F C Cl F Cl
C
F
H
Cl H H

Dash/wedge Fischer Projection

g
bond dwg
Vertical lines go back.
Horizontal lines come out.
out
Vertex = a saturated carbon.
(Carbon not shown!)
Stereochemistry Stereochemistry

Fischer Projections – be careful

CH3 F
CH3
?
?
Wh t happens
What h pp ns if
F Cl F Cl you rotate by 90o H CH3
in the plane of
H the page? Cl
H
A. The rotated drawing g represents
p the CH3 F
same molecule.
H C CH3
B The rotated drawing represents a
B.
F C Cl

new molecule. H Cl
C The
C. Th rotated
t t d drawing
d i h has llostt all
ll
R S
meaning and cannot be interpreted
by a practicall organic chemist. Ans: It “generates” the enantiomer
Stereochemistry Stereochemistry
Be careful w/ Fischer projections.
and now lets address how we name Nomenclature
enantiomers diastereomers,
enantiomers, diastereomers etc.….
etc OH

CH3CH2 CH CH3

CH3 CH3

H
C C
CH3CH2
OH OH
CH3CH2 H

Stereochemistry Stereochemistry

Nomenclature Nomenclature
Cahn Ingold Prelog Priority Rules
Cahn-Ingold-Prelog
To apply:
1. Assign a priority to each atom/group attached
to a chiral center.
center
a. Atoms of higher atomic #.
b Isotopes of higher mass.
b. mass
c. When atoms directly bonded are identical,
step out 1 atom (and again as necessary).
necessary)
2. Redraw so lowest priority points away from
observer; examine remaining 3 groups:
a. If organized in clockwise fashion, R
b If organized in counterclockwise fashion,
b. fashion S
Stereochemistry Stereochemistry
Nomenclature Nomenclature
Cahn Ingold Prelog Priority Rules
Cahn-Ingold-Prelog Cahn Ingold Prelog Priority Rules
Cahn-Ingold-Prelog
c c
F L
Lowest priority F
d c
H F H-atom

C
a Br C
Cl
H d Br Cl b a Br b
a Cl
b
c (S)-bromochlorofluormethane
F
d c a
H F H-atom Br
d a
H Br H-atom
C
a Br Cl b a Br Cl b C
c F Cl b c F Cl b
Stereochemistry (S)-bromochlorofluormethane Stereochemistry
(R)-bromochlorofluormethane

5.4 How many chiral centers are present in

-cadinene??

CH3

H3C
CH(CH
( 3)2

Stereochemistry Stereochemistry
5.5 What is the complete name of the Draw (2S)-1-bromo-2-chloro-3-ethylpentane
following? Br Cl CH2CH3
CH3 Br
H H
H2C CH CH CH2CH3
C CH2 C *
H 3C CH3 a
Cl Cl
H-atom

b H
C
BrCH2 CH(CH2CH3)2 CH(CH2CH3)2
c BrCH2

Stereochemistry Stereochemistry

5.6 Is the following molecule chiral?

H3C Cl
C

H H

C
Cl CH3

Stereochemistry Stereochemistry
Is life too easy for us? Molecules with more than 1 chiral center
Is the following molecule chiral? Maximum number of stereoisomers possible = 2n.
H n = number of asymmetric centers.
H3C Cl Consider 3-bromo-2-butanol HO B
Br

C C
H3C CH CH CH3
Cl CH3
H H H
Plane of HO
H H
OH HO
H
Rotate
R t t180o H3C CH 3 H3C
C about central C Symmetry! C C C

C-C bond
Cl
C CH3
C Cl
C CH3
C C C C
Br Br H3C
H H H
H3C CH 3 Br
In looking for planes of symmetry, do not
restrict yourself wrt rotation about single
bonds 2S, 3R 2R, 3S
Stereochemistry Stereochemistry

5.7 What is the stereoconfiguration of the Molecules with more than 1 chiral center
molecule shown Maximum number of stereoisomers possible = 2n.
HO n = number of asymmetric centers.
H
H3C
C
Consider 3-bromo-2-butanol HO B
Br

H3C CH CH CH3
C
H3C HO H
OH HO H
OH
H H CH 3 H
CH 3
Br H3C H3C
C
C C C

C C C C
Br Br H3C CH 3
H H H H
H3C CH 3 Br Br

2S, 3R 2R, 3S 2S, 3S 2R, 3R

Stereochemistry Stereochemistry
Molecules with more than 1 chiral center Fischer Projections – applied to
HO
H3C
H H
OH
CH 3
HO
H3C
O
H H
OH
CH 3
2,3-dichlorobutane
C Cl Cl
C C C
Max of 4 stereoisomers
H3C CH CH CH3
C C C C
Br Br H3C CH 3
H H H H
H3C CH 3 Br Br

2S, 3R 2R, 3S 2S, 3S 2R, 3R CH3 CH3 5.9 Gives…

H Cl Cl H

• 4 different stereoisomers (22). H Cl Cl H Rotate by

180o.
• 2 pairs of enantiomers.
• 4 pairs of diastereomers CH3 CH3
stereoisomers which are not enantiomers.
Stereochemistry Stereochemistry

Fischer Projections – applied to Fischer Projections – applied to

2,3-dichlorobutane CH3 CH3 CH3 2,3-dichlorobutane
Cl Cl
Cl H
Max of 4 stereoisomers
H Cl H Cl
Max of 4 stereoisomers
H3C CH CH CH3
H Cl Cl H Rotate H Cl
by
CH3 CH3 180o. CH3

Same as original
CH3 CH3 CH3 meso-2,3-dichlorobutane No enantiomer
A meso cmpd
Cl H
A achiral molecule that contains chiral
H Cl H Cl

H Cl Cl H Rotate by H Cl centers.
180o.

CH3 CH3 CH3

Same as original
No enantiomer
Stereochemistry Stereochemistry
A meso cmpd
Fischer Projections – applied to
CH3 CH3 CH3 2,3-dichlorobutane
H Cl Cl H H Cl
Max of 4 stereoisomers
H Cl Cl H Rotate H Cl
by
CH3 CH3 180o. CH3

Same as original
meso-2,3-dichlorobutane No enantiomer
A meso cmpd
CH3 CH3
S R
H Cl Cl H Of 4 possible
S R stereoisomers,
Cl H H Cl
only 3 are unique.
CH3 CH3
Assign (R) or (S) to each stereocenter
Stereochemistry