Chirality
Chirality - the Handedness
of Molecules
Isomers
we concentrate on enantiomers and diastereomers
Enantiomers
 Enantiomers: nonsuperposable mirror images
 as an example of a molecule that exists as a pair of
enantiomers, consider 2-butanol
OH
C H
H3 C
CH2 CH3
Origin al molecu le
HO
H C CH
3
CH3 CH2
Mirror image
Enantiomers
 one way to see that the mirror image of 2-butanol is not
superposable on the original is to rotate the mirror
image
OH
C H
H3 C
CH2 CH3
Original molecule
180°
OH
H C CH
3
CH3 CH2
Mirror image
rotate by 180°
about the
C-OH b on d
OH
H3 C
C CH CH
2
3
H
The mirror image
rotated b y 180°
Enantiomers
 now try to fit one molecule on top of the other so that all
groups and bonds match exactly
OH
The mirror image
turn ed by 180°
C CH CH
2
3
H3 C
H
OH
The original molecule
C H
H3 C
CH2 CH3
 the original and mirror image are not superposable
 they are different molecules
 nonsuperposable mirror images are enantiomers
Enantiomers
 Objects that are not superposable on their mirror
images are chiral (from the Greek: cheir, hand)
 they show handedness
 The most common cause of enantiomerism in
organic molecules is the presence of a carbon with
four different groups bonded to it
 a carbon with four different groups bonded to it is called
a stereocenter
Enantiomers
 If an object and its mirror image are
superposable, they are identical and there is no
possibility of enantiomerism
 such an object is achiral (without chirality)
 An achiral molecule, consider 2-propanol
 notice that it has no stereocenter
OH
C H
H3 C
CH3
Origin al molecu le
OH
H C CH
3
H3 C
Mirror image
Enantiomers
 to see the relationship between the original and its
mirror image, rotate the mirror image by 120°
OH
C H
H3 C
CH 3
Origin al molecu le
120° OH
H C CH
3
H3 C
Mirror image
rotate by 120°
about th e
C-OH bond
OH
C H
H3 C
CH3
The mirror image
rotated b y 120°
 after this rotation, we see that all atoms and bonds of
the mirror image fit exactly on the original
 the original and its mirror image are the same
Enantiomers
 To summarize
 an object that is nonsuperposable on its mirror image is chiral
(it shows handedness)
 the most common cause of chirality among organic molecules
is the presence of a carbon with four different groups bonded
to it
 we call a carbon with four different groups bonded to it a
stereocenter
 an object that is superposable on its mirror image is achiral
(without chirality)
 nonsuperposable mirror images are called enantiomers
 enantiomers, like gloves, always come in pairs
Drawing Enantiomers
 Following are four different representations for one of the
enantiomers of 2-butanol
OH
C H
H3 C
CH2 CH3
(1)
H
H3 C
OH
C
CH2 CH3
(2)
H OH
OH
(3)
(4)
 both (1) and (2) show all four groups bonded to the
stereocenter and show the tetrahedral geometry
 (3) is a more abbreviated line-angle formula; although we
show the H here, we do not normally show them in line-angle
formulas
 (4) is the most abbreviated representation; you must
remember that there is an H present on the stereocenter
Drawing Mirror Images
 on the left is one enantiomer of 2-butanol
 on the right are two representations for its mirror image
(in this case, its enantiomer)
OH
One en antiomer
of 2-b utanol
OH
OH
Alternative rep res entations
for its mirror image
The R,S System
 To assign an R or S configuration
 assign a priority from 1 (highest) to 4 (lowest) to each
group on the stereocenter;
 orient the stereocenter so that the group of lowest
priority is facing away from you
 read the three groups projecting toward you in order
from (1) to (3)
 if reading the groups is clockwise, the configuration is R
(Latin, rectus, straight, correct)
 if reading the groups is counterclockwise, the
configuration is S (Latin: sinister, left)
The R,S System
 The first step in assigning an R or S configuration to a
stereocenter is to arrange the groups on the
stereocenter in order of priority
 priority is based on atomic number
 the higher the atomic number, the higher the priority
Atom or
Grou p
-I
-Br
-Cl
-SH
-OH
-NH2
O
-COH
O
-CNH2
O
-CH
-CH2 OH
-CH2 NH2
-CH2 CH3
-CH2 H
-H
Reason for Priority: First Point of D ifferen ce
(Atomic numbers)
iodine (53)
bromin e (35)
ch lorine (17)
su lfu r (16)
oxygen (8)
nitrogen (7)
carbon to oxygen, oxygen, th en oxygen (6 ->8, 8, 8)
carbon to oxygen, oxygen, th en nitrogen (6 ->8, 8, 7)
carbon to oxygen, oxygen, th en hydrogen (6 ->8, 8, 1)
carbon to oxygen (6 -> 8)
carbon to nitrogen (6 -> 7)
carbon to carbon (6 -> 6)
carbon to hydrogen (6 -> 1)
hydrogen (1)
The R,S System
 Example: assign priorities to the groups in each set
(a) -CH2 OH and -CH2 CH2 OH
O
(c) -CH2 OH and -CH2 CH2 COH
(b) -CH2 CH2 OH and -CH2 NH2
(d) -CH2 NH2
O
and -CH2 COH
The R,S System
 Example: assign priorities to the groups in each set
(a) -CH2 OH and -CH2 CH2 OH
-CH2 OH
-CH2 CH2 OH
Higher priority Lower priority
O
(c) -CH2 OH and -CH2 CH2 COH
O
-CH2 OH
-CH2 CH2 COH
Higher priority Low er priority
(b) -CH2 CH2 OH and -CH2 NH2
-CH2 CH2 OH
-CH2 NH2
Lower priority Higher priority
(d) -CH2 NH2
O
and -CH2 COH
O
-CH2 NH2
-CH2 COH
Higher priority Low er priority
The R,S System
 example: assign an R or S configuration to each
stereocenter
OH
(a)
C
H
H3 C
CH2 CH3
2-Bu tanol
H2 N H
(b)
C
H3 C
COOH
Alanin e
The R,S System
 example: assign an R or S configuration to each
stereocenter
1
(a)
3
H3 C
OH
C
4
R
H
CH2 CH3
2
(R)-2-Butan ol
R
1
4
H2 N H
(b)
R
C 2
H3 C
COOH
3
(R)-Alanine
R
The R,S System
 Because enantiomers are different compounds, each must
have a different name
 here are the enantiomers of the over-the-counter drug
ibuprofen
H CH3
COOH
The in active enantiomer
of ib uprofen
H3 C H
HOOC
The active enan tiomer
 the R,S system is a way to distinguish between enantiomers
without having to draw them and point to one or the other
The R,S System
 returning to our original three-dimensional drawings of
the enantiomers of ibuprofen
4
3
3
H CH3
1
2
COOH
R
(R)-Ibuprofen
(the in acti ve en antiomer)
H3 C H4
1
2
HOOC
S
(S)-Ibuprofen
(the acti ve enenti omer)
Chirality in Biomolecules
 a molecule and its enantiomer or one of its
diastereomers elicit different physiological responses
 as we have seen, (S)-ibuprofen is active as a pain and
fever reliever, while its R enantiomer is inactive
 the S enantiomer of naproxen is the active pain
reliever, but its R enantiomer is a liver toxin!
H3 C H
HOOC
H3 C H
HOOC
OCH3
(S)-Ib uprofen
(S)-N aproxen
Stereocenters
 A molecule with n stereocenters has a maximum
number of 2n stereoisomers
 a molecule with one stereocenter, 21 = 2 stereoisomers
(enantiomers) are possible
 for a molecule with two stereocenters, a maximum of 22
= 4 stereoisomers (two pair of enantiomers)
 for a molecule with three stereocenters, a maximum of
23 = 8 stereoisomers (four pairs of enantiomers) is
possible
 and so forth
Fischer Projection Formulas
 Fischer Projection: show configuration of chiral
molecules in two-dimensional representation
 Vertical bonds are directed away
 Horizontal bonds are directed toward you
OH
H
H3CH2C
H
OH
CH2CH3
H
OH
CH2CH3
Enantiomers & Diastereomers
 2,3,4-Trihydroxybutanal
O
* *
HOCH2 -CH-CH-CH
OH OH
two stereocenters; 22 = 4 stereoisomers exist
Two Stereocenters
 2,3,4-trihydroxybutanal
CHO
CHO
H
C
OH HO
C
H
H
C
OH HO
C
H
CH2 OH
CH2 OH
(a)
(b)
A p air of enantiomers
(Erythreose)
CHO
CHO
H
C
OH HO
C
H
HO
C
H
C
OH
H
CH2 OH
CH2 OH
(c)
(d)
A pair of en antiomers
(Threos e)
 diastereomers: stereoisomers that are not mirror images
 (a) and (c), for example, are diastereomers
Meso Compounds
 Meso compound: an achiral compound possessing two or
more stereocenters
 tartaric acid
 two stereocenters; 2n = 4, but only three stereoisomers exist
COOH
COOH
H
C
OH HO
C
H
H
C
OH HO
C
H
COOH
COOH
A meso compound
(plane of symmetry)
COOH
COOH
H
C
OH HO
C
H
HO
C
H
C
OH
COOH
H
COOH
A pair of enantiomers
Stereoisomers
 example: mark all stereocenters in each molecule and
tell how many stereoisomers are possible for each
OH
(a) CH2 =CHCHCH2 CH3
HO
(d)
HO
(b)
CH3
CH3
(e)
OH
(c)
NH2
OH
COOH
NH2
OH O
OH
OH
(f)
NH2
Stereoisomers
 example: mark all stereocenters in each molecule and
tell how many stereoisomers are possible for each
 solution:
OH
(a) CH2 =CHCHCH2 CH3
*
21 = 2
HO
* COOH
HO
NH2
(d)
21 = 2
OH O
OH
(b)
CH3
CH3
21 = 2
*
*
(e)
*
22 = 4
(c)
OH
* *
OH
NH2
2
2 =4
* OH
(f)
* NH2
22 = 4
Three Or More Stereocenters
 how many stereocenters are present in the molecule on
the left?
 how many stereoisomers are possible?
 one of the possible stereoisomers is menthol
 assign an R or S configuration to each stereocenter in
menthol
OH
2-Is op ropyl-5-meth ylcyclohexanol
OH
Menthol
Three Or More Stereocenters
R
*
*
*
OH
2-Is op ropyl-5-meth ylcyclohexanol
23 = 8 possible stereoisomers
S
R
OH
Menthol
Stereoisomers
 The 2n rule applies equally well to molecules with
three or more stereocenters
H
H3 C
H3 C
*
HO
*
*
*
*
* *
*
Cholesterol h as 8 stereocenters;
256 s tereoisomers are poss ible
H3 C
H
H
HO
H
H
H
Th is is th e stereoisomer found in
human metabolism