120

100
100

80
Nilai

60 56

44

40
25

20
35 3 4 24 1
4 35 2 4 24 1
4 2
5
1 3 13 2 3 23 1 2.5 12.5
0
al n si si al n si si is n si si s n si l i
m ro n a m ro n a w ra k a g u t a a ota i la
r kt na ridi
s or ek
t
na ridis Le ku Ind
u is u Ik
a di
s T N
Fo Ele o F l o a u rid G s ri
tan ah R es Hi
b
tan ah
E
R es Hi
b
as a n
f ek Hi
b
m
a
e ni H ib
B d a J
ua Ar tu
r ua Ar tu
r
a n E
fe
k N
M k M k i f E
ru ru at
St St g
ne
rt o
k
e le
Ke
ek Nilai Rata2 Mahasiswa
Ef
Nilai Acuan
Konsep
 10
20
30
40
50
60
70
80

0
Muatan Formal

66 67
Struktur

62
Resonansi

22
Muatan Formal
57
53

Struktur
42
Resonansi
25
Basa Lewis
43 43
35

Efek Induksi
70
Persentase Keberhasilan

Nama Gugus
67

48

Hibridisasi
32
44 44

Nilai
Persentase Keberhasilan
OPTICAL ACTIVITY

PLANE-POLARIZED LIGHT
 PLANE-POLARIZED LIGHT BEAM
wavelength All sine waves (rays) in the
single  beam aligned in same plane.
ray or
photon

SIDE
. END
VIEW
VIEW
polarized beam
A beam is a collection
of these rays.
NOT PLANE-POLARIZED
frequency (  ) Sine waves
are not aligned
 = c in the same
 plane.
c = speed of light unpolarized
beam
 Optically Active
• Refers to molecules that interact with plane-
polarized light

Jean Baptiste Biot

French Physicist - 1815
He discovered that some natural substances
(glucose, nicotine, sucrose) rotate the plane
of plane-polarized light and that others did not.
TYPES OF OPTICAL ACTIVITY
new older

Dextrorotatory (+)- d-

Rotates the plane of plane-polarized light

to the right.
new older

Levorotatory (-)- l-

Rotates the plane of plane-polarized light

to the left.
 Specific Rotation []D
This equation corrects
 for differences in cell
[]Dt =
length and concentration.
cl Specific rotation calculated
in this way is a physical
property of an optically
active substance.
 = observed rotation You always get the same
c = concentration ( g/mL ) value of []Dt
l = length of cell ( dm )
D = yellow light from sodium lamp
t = temperature ( Celsius )
 The Polarimeter
observed
plane-polarized rotation
light  
Na lamp
sample cell

0
0
0
0
0

plane is
polarizer analyzer
rotated
chemistry
nerd

rotate to null
STEREOISOMERS

ENANTIOMERS
PASTEUR’S DISCOVERY

Louis Pasteur 1848

Sorbonne, Paris

2-
+
Na O O C CH CH CO O NH 4+
HO OC CH CH CO OH
OH OH OH OH

tartaric acid sodium ammonium tartrate

( found in wine must )
Pasteur crystallized this
substance on a cold day.
 Crystals of Sodium Ammonium Tartrate
Pasteur found two
hemihedral faces different crystals.

mirror
images

Biot’s results : (+) (-)

Louis Pasteur separated these and gave them to Biot to measure.
 Enantiomers
non-superimposable mirror images
(also called optical isomers)

W W

C C
X Y Y X
Z Z

Pasteur decided that the molecules that made the crystals,

just as the crystals themselves, must be mirror images.
Each crystal must contain a single type of enantiomer.
 Pasteur’s hypothesis eventually led to the discovery
that tetravalent carbon atoms are tetrahedral.

Van’t Hoff and C tetrahedral

LeBel (1874) carbon

Only tetrahedral geometry can lead to mirror image

molecules:

C C

Square planar, square pyrimidal or trigonal pyramid

will not work:
C C C
 ENANTIOMERS HAVE
EQUAL AND OPPOSITE
ROTATIONS

W Enantiomers W

C C
X Y Y X
Z Z

(+)-nno (-)-nno
dextrorotatory levorotatory
ALL OTHER PHYSICAL PROPERTIES ARE THE SAME
 O
H OTARTARIC ACID
H meso

H
OOC fromC
fermentation
O O H of wine
H H
Enantiomers
O
H O
H O
H O
H
H
OOC H H COO
H
H C
OOH H
OOC H

(+)-tartaric acid (-)-tartaric acid

enantiomers

O
H O
H meso ALSO FOUND
(as a minor component)
H
OOC COO
H
H H []D = 0
more about this
meso -tartaric acid compound later
O
H O
H O
H O
H
 TARTARIC ACID
(-) - tartaric acid (+) - tartaric acid
[]D = -12.0o []D = +12.0o
mp 168 - 170o mp 168 - 170o
solubility of 1 g solubility of 1 g
0.75 mL H2O 0.75 mL H2O
1.7 mL methanol 1.7 mL methanol
250 mL ether 250 mL ether
insoluble CHCl3 insoluble CHCl3
d = 1.758 g/mL d = 1.758 g/mL

meso - tartaric acid

[]D = 0o solubility of 1 g
mp 140o 0.94 mL H2O
d = 1.666 g/mL insoluble CHCl3
 RACEMIC MIXTURE
an equimolar (50/50) mixture of enantiomers

[ ]D = 0 o

the effect of each molecule is

cancelled out by its enantiomer
CHIRALITY, SYMMETRY PLANES
AND ENANTIOMERS
PLANES OF SYMMETRY
A SYMMETRIC OBJECT HAS A PLANE OF SYMMETRY
- ALSO CALLED A MIRROR PLANE

plane of
symmetry

mirror
plane
IF AN OBJECT HAS A PLANE OF SYMMETRY,
ITS MIRROR IMAGE WILL BE IDENTICAL

IDENTICAL MIRROR IMAGES WILL SUPERIMPOSE

(MATCH EXACTLY WHEN PLACED ON TOP OF EACH OTHER)
CHIRALITY
 An object without symmetry is CHIRAL
no symmetry

The mirror image

of a chiral object is
different and will not
superimpose on the
original object.
OBJECTS WHICH ARE CHIRAL
HAVE A SENSE OF “HANDEDNESS”
AND EXIST IN TWO FORMS
An object with symmetry is ACHIRAL ( not chiral).

The mirror image of an achiral

object is identical and will
superimpose on the original object.

plane of
symmetry
ENANTIOMERS

STEREOISOMERS
 ENANTIOMERS
non-superimposable
mirror images
Cl Cl
rotate

H F F
Br Br H
this molecule
is chiral Cl
note that the fluorine

H Br and bromine have been

interchanged in the

do interchanges in class
F enantiomer
 STEREOISOMERS

ENANTIOMERS are a type of STEREOISOMER

Stereoisomers are the same constitutional isomer,

but have a difference in the way they are arranged
in three-dimensional space at one or more of their
atoms.

and remember …...

 ENANTIOMERS HAVE
EQUAL AND OPPOSITE
ROTATIONS

W Enantiomers W

C C
X Y Y X
Z Z

(+)-nno (-)-nno
dextrorotatory levorotatory
ALL OTHER PHYSICAL PROPERTIES ARE THE SAME
STEREOGENIC CARBON ATOMS
 STEREOCENTERS

One of the ways a molecule can be chiral is to have a

stereocenter.

A stereocenter is an atom, or a group of atoms,

that can potentially cause a molecule to be chiral.

stereocenters - can
give rise to chirality
STEREOGENIC CARBONS
( called “chiral carbons” in older literature )

Cl This is one type of ….

stereocenter
…. others are possible

H F
Br
H
A stereogenic carbon is tetrahedral F
and has four different groups attached. Cl
Br
F
Cl ACHIRAL
Br
The plane of the paper
is a plane of symmetry

F F

Br Cl Cl
Cl Cl Br

TWO IDENTICAL GROUPS RENDERS A

TETRAHEDRAL CARBON ACHIRAL
ONE PAIR OF ATOMS ATTACHED TO A TETRAHEDRAL
CARBON IS IN A PLANE PERPENDICULAR TO THE
OTHER PAIR
plane 1

plane 2

Look at your
F model set !
Cl
Br
TWO VIEWS OF THE PLANE OF SYMMETRY

plane of
symmetry

F F

Cl Cl
Br Cl
Br
Cl
F side edge
Cl
Br view view
 ACHIRAL
A CARBON ATOM WITH THREE SIMILAR
GROUPS IS ALSO ACHIRAL …..

Cl Cl

Br Cl Cl
Cl Cl Br

Cl
Br
 plane of
symmetry
Cl
Cl

Cl Cl
Br Cl
Br
Cl
side view edge view
 CONFIGURATION

ABSOLUTE CONFIGURATION ( R / S )
 CONFIGURATION

The three dimensional arrangement of the

groups attached to an atom

Stereoisomers differ in the configuration at one or

more of their atoms.
 CONFIGURATION - relates to the three dimensional
sense of attachment for groups attached to a chiral
atom or group of atoms (i.e., attached to a stereocenter).

1 2 2 counter
clockwise 1
clockwise
C C
4 4
3 3
view with
substituent
of lowest
priority in
back
R (rectus) S (sinister)
SPECIFICATION OF CONFIGURATION

Enantiomers are assigned a CONFIGURATION

using the same priority rules we developed for
E/Z stereoisomers.

1. Higher atomic number has higher priority.

2. If priority cannot be decided based on the first

atom attached move to the next atom, following
the path having the highest prioity atom.
3. Expand multiple bonds by replicating the atoms
attached to each end of the bond.

CAHN-INGOLD-PRELOG
SEQUENCE RULE
 Naming Enantiomers
Cahn-Ingold-Prelog R,S-Nomenclature
Label all substituents at stereocenter, starting at
point of attachment, according to the sequence
rules in order of decreasing priority: a, b, c, d
(note color scheme). Look down C-d bond:
a

a, b, c clockwise : R c C d
R
b
a, b, c counterclockwise : S
Cahn-Ingold-Prelog
1966
 Sequence Rules
1. Order by atomic number, i.e. H = 1, lowest.
Hd

* Exception: lone pair,

a
I
C c
# “zero”. E.g., amines:
N :
R CH3
d
Br
b
2. If same priority at first atom: Go to first
point of difference.
CH3
-CH2CH3 -CCH3
‹H -CH2CH2SH -CH2CH2SCH3 ‹
CH3 D
-CH2CH2OH
‹ -CHCH3 -CH2CBr3
‹ -CHCH 3
3. Multiple bonds: Add double or triple
representations of atoms at the respective other
end of the multiple bond.

C C
H H H H C C C C
C C C C
C C
C C
N C
C O H C O C N C N
H O C N C
Procedure for Assignment
of R, S
Fischer Projection: A flat stencil
Br H
Br
CH3 C CH2CH3
H

Br
Eyes in the
plane of the CH3 CH2CH3
board
H

Depending on your starting dashed-wedged line

structure, several Fischer projections are possible
for the same molecule.
Fischer Projections
Rules for handling Fischer projections:
1. Don’t rotate.
2. The mutual exchange of
any pair gives the other
enantiomer
Therefore: Two exchanges leave absolute
configuration. Example: (2R)-Bromobutane

Br CH 3 C H 2CH 3
R R R
CH3 CH2CH3 Br H H Br

H C H 2CH 3 C H3
This procedure can be used to readily assign R,S :

Do double exchanges to place d on top.

Example:
a Br a d
c b
CH3 CH2CH3 c b b c

H a
R !!
d
d

Note: There are three possible arrangements for each, R orS, e.g., R :

d R d R d R

c a b c a b

b a c
Problem: Are these two molecules the same
or opposite enantiomers? R or S ?

F F

H CH3 I H

I CH3
Solution:
b
F F d

H CH3 H CH3 b a
d c S
I I c
a

b
F F d

I H I H c b
a d S
CH3 CH3 a
c
Two Stereocenters: The Chlorination of 2-
Bromobutane
Cl
Generates:
* Cl2, hν ** RR, RS SR, SS
-HCl
Br Br
Four stereoisomers

RR SS and RS SR are enantiomer pairs

Diastereomers

Diastereomers are stereoisomers that are not

image-mirror-image-related.
 Bromochlorofluoroiodomethane

1 1
I I
4
F C 4
C
2 F
Cl Br Br Cl
3 3
2

R S
Enantiomers
 NUMBER OF
STEREOISOMERS POSSIBLE
 How Many Stereoisomers Are
Possible?

maximum number of stereoisomers

sometimes fewer
than this number
= 2 n
,
will exist

where n = number of stereocenters

(sterogenic carbons)
 CH2OH OH RR
RS
CH3 *
C CH2 CH CH CH3 SR
* SS
CH3 CH3
22 = 4 stereoisomers
CH3
RRR RSS
* RRS SRS
RSR SSR
*
* OH SRR SSS

CH3 CH
CH3 23 = 8 stereoisomers
 FINDING STEREOCENTERS
(STEREOGENIC CARBONS)

O O O
CH3
*
*
CH3
CH3
plane
( indicates no stereoisomers )

stereoisomers (max) :
20 = 1 21 = 2 21 = 2
 FINDING STEREOCENTERS
(STEREOGENIC CARBONS)

O O O
CH3 CH3 CH3
* * *
* *
* CH3 CH3
CH3
plane
( but only if cis )

stereoisomers (max) :
22 = 4 22 = 4 22 = 4
FINDING STEREOCENTERS (CHIRAL CARBONS)

CH3
*
CH3

* *
CH3 CH3
*
*
* * CH3
HO *
H
n=8
28 = 256
TYPES OF ISOMERS
 ISOMERS CONSTITUTIONAL
Different compounds ISOMERS
with the same Isomers with a different
molecular formula order of attachment of
the atoms in their
molecules
each isomer could
have stereoisomers
ENANTIOMERS
STEREOISOMERS Stereoisomers whose
molecules are non-
Isomers with the same order
superimposible mirror
of attachment, but a different
images of each other
configuration (3D arrangement)
of groups on one or more of
the atoms DIASTEREOMERS
Stereoisomers whose
double bond or ring molecules are not mirror
with a ring images of each other
cis/trans both can apply
ISOMERS
(geometric) TYPES OF ISOMERISM
 MOLECULES WITH
TWO STEREOCENTERS

DIASTEREOMERS / MESO
 2-Bromo-3-chlorobutane

* *
C
H
3C
HC
H
CH
3 22 = 4 stereoisomers
4 3 2 1

C
lBr possible
SR SS
RS RR
C
lB
r B
rC
l
C
H
3When comparingCH butanes,C
3 H
the3comparisons C H 3
H
are H
done best using the eclipsedH H
conformation.

The C lB r and planes of symmetry

relationships BrC l
are not easily seen in other conformations.
C
H
3 H H C
H
3
HC
H
 CH3CHCHCH3
2-Bromo-3-chlorobutane
Cl Br

mirror
Cl Br Br Cl
S R S R
CH3 CH3 CH3 CH3
H H H H
enantiomers 1
diastereomers
Cl Br Br Cl
S S R R
CH3 H H CH3
H CH3 CH3 H
enantiomers 2
Models of the Isomers of 2-Bromo-3-chlorobutane
(methyl groups are reduced to a single red atom)

Br

Cl
CH3
enantiomers-1
H

diastereomers

enantiomers-2
 2,3-Dichlorobutane
( Replace the Bromine with a second Chlorine )

H H
* *
CH3CHCHCH3 CH3 C C CH3
Cl Cl Cl Cl
(2n = 4)

Cl Cl Cl Cl
Now there is the possibility of a plane of symmetry.
CH 3 CH CH
3 reduces CH
3the number of 3
The existence of a plane
H H H H
stereoisomers that are possible.
You will Cl find
not Cl all 2n (= 4) stereoisomers.
Cl Cl
CH3 H H CH3
 CH3CHCHCH3
C2,3-Dichlorobutane
l Cl

Cl Cl Cl Cl
S R mirror image
CH3 CH3 CH3 is identical CH3
H H H H
meso
diastereomers
Cl Cl Cl Cl
S S R R
CH3 H H CH3
H CH3 CH3 H
enantiomers
 MESO ISOMER

plane of symmetry
mirror

Cl Cl Cl Cl
S R
CH3 CH3 CH3 CH3
H H H H

Meso isomer - has a plane of symmetry and the

mirror image is identical to the
original molecule.
 Models of the Isomers of 2,3-Dichlorobutane
(methyl groups are reduced to a single red atom)

Cl
CH3
H meso

diastereomers

enantiomers
 CONCLUSION
2n = the maximum
number
When a molecule has
1. multiple stereocenters and
2. there is a possibility of an arrangement
with a plane of symmetry
you will not always find all of the 2n stereoisomers
that are possible.

Some of the stereoisomers may be meso isomers,

and their mirror images will be superimposable
(identical) - this will eliminate at least one of the
possible stereoisomers, and sometimes more.
 PHYSICAL PROPERTIES OF
ENANTIOMERS, DIASTEREOMERS
AND MESO COMPOUNDS
 ENANTIOMERS HAVE
REMEMBER : EQUAL AND OPPOSITE
ROTATIONS

W Enantiomers W

C C
X Y Y X
Z Z

(+)-nno (-)-nno
dextrorotatory levorotatory

ALL OTHER PHYSICAL PROPERTIES ARE THE SAME

 DIASTEREOMERS
IN CONTRAST : MAY HAVE
DIFFERENT ROTATIONS

AND ALSO DIFFERENT PHYSICAL PROPERTIES

 O
H O
H mesoTARTARIC ACID HAS THREE
STEREOISOMERS
from fermentation of wine
H
OOC COO
H
H H
Enantiomers
O
H O
H O
H O
H
H
OOC H H COO
H
H C
OOH H
OOC H

(+)-tartaric acid (-)-tartaric acid

enantiomers

O
H O
H meso Diastereomers

H
OOC COO
H
H H
meso -tartaric acid
O
H O
H O
H O
H
 TARTARIC ACID
Enantiomers

(-) - tartaric acid (+) - tartaric acid

[]D = -12.0o []D = +12.0o
mp 168 - 170o mp 168 - 170o
solubility of 1 g solubility of 1 g
D
0.75 mL H2O 0.75 mL H2O i
1.7 mL methanol 1.7 mL methanol a
250 mL ether 250 mL ether s
t
insoluble CHCl3 insoluble CHCl3 e
d = 1.758 g/mL d = 1.758 g/mL r
e
o
meso - tartaric acid m

[]D = 0o
e
solubility of 1 g r
0.94 mL H2O s
mp 140o
d = 1.666 g/mL insoluble CHCl3
CIS / TRANS RINGS

DIASTEREOMERS
 1-Bromo-2-chlorocyclopropane
note that the cis/trans isomers are also diastereomers
Br R Cl Cl R Br
S S
cis

enantiomers
diastereomers
Br Br
R R S S
trans
Cl Cl

enantiomers
 1,2-Dibromocyclopropane
mirror image identical

Br Br Br Br
cis

meso
diastereomers

Br Br
trans
Br Br

enantiomers
DISUBSTITUTED CYCLOHEXANES

USING PLANAR RINGS FOR STEREOCHEMICAL ANALYSIS

 1-Bromo-2-chlorocyclohexane
cyclohexanes may be analyzed using planar rings

Br Cl Cl Br cis

enantiomers
diastereomers

Br Br trans

Cl Cl
enantiomers
 1,2-dichlorocyclohexane
mirror image identical

Cl Cl Cl Cl cis

meso
diastereomers

Cl Cl trans

Cl Cl
enantiomers
DOT NOTATION CAN ALSO BE USED

plane of symmetry
is readily seen

Cl Cl Cl Cl Cl Cl

cis (meso) trans (enantiomers)

 Isomers of Dichlorocyclohexane
DOTS MAKE FIGURING CYCLIC ISOMERS EASY

cis trans

Cl
Cl
Cl Cl Cl Cl Cl Cl
1,1-dichloro meso enantiomers
cis 1,2-dichloro
Cl Cl
cis trans
both meso Cl Cl Cl
trans
Cl Cl Cl
Cl Cl
meso enantiomers
1,4-dichloro 1,3-dichloro
INTERCHANGING GROUPS

SOLVING A PROBLEM
 INTERCHANGES
ONE STEREOCENTER

CH3 CH3

C C

Br H F H
F Br
enantiomer

ODD: 1..3..5…etc interchanges = enantiomer

EVEN: 2..4..6...etc interchanges = original compound
 PROBLEM: ARE THESE IDENTICAL
OR ARE THEY ENANTIOMERS?
YOU CAN USE
CH3 H INTERCHANGES

C C

Br H CH3 F
F Br

H H
CH3 Br 2
1 C
C C C
CH3 F
Br H CH3 H CH3 Br Br
F F F
ENANTIOMER SAME ENANTIOMER
3
 AN EASIER WAY IS TO DETERMINE THE
ABSOLUTE CONFIGURATION OF EACH MOLECULE

CH3 H TIP HYDROGEN

ROTATE TO BACKWARDS
THE RIGHT
C C

Br H CH3 F
F Br
3 1 Br
CH3
H ENANTIOMERS H

S R
Br F CH3 F
1 2 3 2
 C
lCl
MORE THAN ONE STEREOCENTER
C
lCl C l C
l
To form an enantiomer you must
interchange all of the stereocenters.
C
H3 C H 3 C H 3 C
H3
H H H H

C
lCl C
lCl
C
H3 H H CH3
H C
H3 C
H3 H

two stereocenters
enantiomer
two interchanges
 If a compound has more than one stereocenter,
C Hand
3C H C Honly
you C Hinterchange
3 one of them,
you will form a distereomer.
Cl Cl

Cl Cl Cl Cl
C H3 CH3 C H3 CH3
twoHstereocenters
H
one interchange
H H

Cl Cl Cl Cl
CH3 H
diastereomer H C H3
H CH3 CH3 H
 COPING TECHNIQUES
IF HYDROGEN IS NOT IN BACK - REVERSE YOUR RESULT !

1
Cl
3 2
CH3 F =S ( after reversal )

REDUCTIO AD NUMERAE (reduce to a set of numbers)

1 2
=S
2 1
3 4
4 two 3
interchanges
 THERE ARE MANY METHODS
THAT LEAD TO A SOLUTION

THERE IS NO SINGLE CORRECT METHOD

TO SOLVE A STEREOCHEMICAL PROBLEM

USE WHATEVER METHOD WORKS BEST FOR YOU

 RELATIONSHIPS
AMONG STEREOISOMERS
COMPARING TWO STEREOISOMERS

Two
Stereoisomers

nonsuperimposable not
mirror images mirror images

Enantiomers Diastereomers
DETERMINING CHIRALITY / OPTICAL ACTIVITY

molecule has one or

more stereocenters
no plane of plane of
symmetry symmetry
mirror image
superimposes
no yes

has an enantiomer is meso

is chiral is achiral

optically optically
active inactive
FISCHER PROJECTIONS
“Sawhorse” Projection EVOLUTION OF THE
CHO FISCHER PROJECTION
HOCH2 OH
H

Fischer Projection
Orient the
main chain CHO CHO
vertically with
the most H OH H OH
oxidized group
at the top. CH2OH CH2OH
Substituents will Main chain bends
stick out toward away from you
you like prongs
 CH3

OH H OH
ORIENTATION OF H H OH
THE MAIN CHAIN H OH
AND THE
SUBSTITUENTS CH3
IN A FISCHER
PROJECTION
OH
H

H OH
continuation
of the main chain
INCREASING OXIDATION STATE
C=O on carbon-2 increases
the priority of C-OH

CH3 CH2 OH CH OH CHO COOH

C O O O
C C
H OH

increasing oxidation state

In the Fisher projection the main chain is oriented

with the most highly oxidized group at the top.
rotate CH3
90o
H Cl
Cl Br main chain in red

CH3 CH3
H H
orient main chain H Br
vertically

CH3 CH3
H
Cl Cl

Br convert to
Br
H Fischer CH3
CH3 Projection
OPERATIONS WITH FISCHER PROJECTIONS
Mirror images (enantiomers)
CHO CHO are created by switching
OH HO substituents to the other side.

OH HO
This is equivalent to turning
CH2OH CH2OH the molecule over like a
pancake.

CHO enantiomers CH2OH

O H
diastereomers HO
All stereocenters must be
OH HO switched to get an enantiomer
CHO
CH2OH CH3 (the mirror inverts them all).
OH
HO
If you switch only some of the stereocenters,
CH2OH not all of them, you get a diastereomer.
OPERATIONS WITH FISCHER PROJECTIONS

CHO CH2OH

. OH
OH
HO
HO
CH2OH CHO
180o

Rotation by 180o in the plane

No other angle of rotation
of the paper does not change
is allowed.
the molecule.

Rotation can be used for comparisons …..

Does A have an enantiomer A* ?

A CH3 A* CH3 C H3
Br Br 2) rotate Br
Br Br Br
CH3 CH3 CH3
1) reflect

3) compare

NO !
 THE MOLECULE WAS MESO !

A CH3 The molecule did not have

an enantiomer because it
Br was not chiral.

Br It had a plane of symmetry,

rendering it a meso molecule.
CH3
plane of symmetry
 CHO CHO
OH HO ENANTIOMERS
OH HO
OH HO all stereocenters
OH HO
have been
inverted HOME STUDY
CH 2 OH CH2 OH
Can you find all 16
(2n = 16) stereo-
CHO CHO CHO CHO isomers? Group
HO OH OH OH them as pairs of
enantiomers. Do
OH HO OH OH
not repeat any!
OH OH HO OH
OH OH OH HO
CH2 OH CH 2 OH CH 2 OH CH 2 OH
CHO CHO CHO
HO OH OH DIASTEROMERS
HO HO HO
only some
OH HO OH stereocenters
OH OH HO have been
CH2 OH CH2 OH CH 2 OH inverted
FURTHER HOME STUDY

Find all of the stereoisomers for this compound. Group all

enantiomers in pairs. Are there any meso stereoisomers?

COOH
OH
OH Will you find 16 (24 = 16)
OH stereoisomers? Why or
why not?
OH
COOH
 DETERMINATION OF
R / S CONFIGURATION
IN FISCHER PROJECTIONS
 PLACE THE PRIORITY=4 GROUP IN ONE OF THE VERTICAL
POSITIONS, THEN LOOK AT THE OTHER THREE

2 4
#4 at top position
CHO H
1
4 H OH OHC CH2OH
2 3
CH2OH OH R
3 1
alternatively: BOTH IN BACK
SAME RESULT
2 1
CHO 3 R OH 2
1 HOCH2 CHO
4 H OH
CH2OH 4 H
3 #4 at bottom position
 FOR THE MENTALLY AGILE
WHY BOTHER INTERCHANGING?
JUST REVERSE YOUR RESULT!

Same molecule
as on previous
2
slide. S reverse R
CHO
H OH 1 Same result
4
as before.
CH2OH
3

H coming
toward you
CYCLIC ROTATION OF GROUPS IN A
FISCHER PROJECTION
YOU MAY FIX ONE GROUP AND THEN ROTATE THE OTHER THREE

2 4
CHO H
1 2
4 H OH rotate HO CHO
1
CH2OH CH2OH R configuration
3 fixed 3
2
CHO
Any of the four 1
H OH This rotation does not
groups may be 4
fixed change the molecule.
fixed.
CH2OH
3
OTHER EXAMPLES
 3- Chloro-2-butanol

enantiomers-1 enantiomers-2

CH3 CH3 CH3 CH3

OH HO HO OH
Cl Cl Cl Cl
CH3 CH3 CH3 CH3

diastereomers
 2,3-Dichlorobutane

enantiomers
CH3 CH3 CH3 CH3
Cl Cl Cl Cl
Cl Cl Cl Cl
CH3 CH3 CH3 CH3

meso

diastereomers
STEREOCENTERS OTHER THAN
STEREOGENIC CARBON
 TETRAHEDRAL ATOMS
NON-CARBON STEREOCENTERS

STEREOGENIC CARBONS are not

the only possible stereocenters in a molecule.

Any atom which is tetrahedral with four different

groups has the potential to be stereogenic.

CH3
CH 2 CH3 CH3
Si H +N +P
H
CH 3
CH 2 CH3 CH2 CH3
CH 2 CH 2 CH3
PYRIMIDAL ATOMS WITH AN
UNSHARED PAIR

Pyrimidal atoms can be stereocenters.

.. .. ..
P CH 3 -O S + Cl N CH P h
CH 3 2
CH 2 CH 3 F CH 2 CH 3

If the atoms do not invert (see next slide) these

molecules will be chiral.
 INVERSION OF SMALL AMINES
Small amines (those with H, CH3, or CH2CH3 groups)
exhibit fast inversion rates:

CH3
.. CH2CH3
H
N
N
CH 3 CH 2 CH 3
.. H
 INVERSION OF SMALL AMINES

.... CH3 CH 2 : = priority 4

H CH3
S N
N
CH3 CH 2 CH3 R RACEMIC MIXTURE
H
.. OF ENANTIOMERS

If fast inversion occurs, a pyrimidal nitrogen will not be an

active stereocenter.

With larger groups, the rate of inversion slows.

If the groups are large enough, inversion stops completely.

When there is no inversion, an amine with three different

groups attached will be a stereocenter.
A CHIRAL AMINE IN ACID SOLUTION
In acid solution, fast inversion may occur if one of the
attached groups is a hydrogen atom (H).

PROTON EXCHANGE
H
S
.. H
N
CH 2 CH2 CH3
+ +
+H +N -H
N H H R
CH2 CH2 CH 3 CH2 CH 2 CH 3 ..
amine 1 ammonium ion amine 2

Removal of a different hydrogen (blue) from the ammonium

ion than the one added (red), causes a change (inversion)
of configuration.
BICYCLIC AMINES ARE USUALLY RIGID
..... and they do not invert

CH3
.. The nitrogen is rigidly held in
*
N the bicyclic rings and cannot
* invert.
NOTE: Without the exo methyl group
CH3 there would be a plane of symmetry
* * and the molecule would be meso.
H
N*
Tröger’s base
N
* []D = 287o
The rings cannot invert.
AZIRIDINES DO NOT INVERT
Aziridine = a three-membered ring
containing a nitrogen atom.

.. CH 3
OCH 3
*N *: N CH 3
CH 3 O * *
H H
trans cis
diastereomers
This amine does not invert even at 200o

The transition state would be planar,

requiring a 120o angle.
STEREOCENTERS THAT DO NOT
INVOLVE A STEREOGENIC ATOM
 NOT ALL STEREOCENTERS ARE ATOMS
Sometimes a group of atoms (none of which is a
stereocenter itself) can confer chirality.

Cl Cl
C CH 3 H3 C C remember that
C C C C an allene has a
F H H F twist in the center

The allene group (C=C=C) is a stereocenter.

An allene is chiral when four different groups are
attached ..... try it with any two groups the same!

Also notice that this group is a stereocenter, and

it has no stereogenic (chiral) carbon atoms.
 COMPARISON OF THE ALLENE AND
STEREOGENIC CARBON STEREOCENTERS

The allene group is just like a stretched out

tetrahedral carbon.
C l CC l l C l C l CC l l
C H 3 HC 3 C C C CC C C C C C H C 3 C C C CH H H3 C3 3 C H H 3 3 CC C CC C C C CC
H F H FF H F HH H HH F FF

remember the
twist

both ends are

perpendicular
 SPIRO COMPOUNDS CAN ALSO BE CHIRAL

CH3 H3 C

H H

F F
Cl Cl
enantiomers

CH 3 H3 C C H 3 H 3 C
F F F

Cl C l H H H H Cl

enantiomers
 HEPTIHELICENE
has no stereocenters - all sp2 atoms
six rings join seven rings
compare: perfectly overlap

coronene heptihelicene
(completely planar) heptihelicene has an enantiomer
(makes a helix which is chiral)
has no enantiomer helices may be right- or left-handed
trans - CYCLOOCTENE
( Remember that this is the smallest ring
which can contain a trans double bond.)

H H

H H

enantiomers

This molecule has no stereocenters,

but it is chiral.

The enantiomers have either a

right-handed or a left-handed twist.
SUMMARY
THERE IS NO REQUIREMENT FOR ATOMIC
STEREOCENTERS FOR A MOLECULE TO BE CHIRAL

Stereogenic Carbon Atoms (or P, or N, or S atoms)

are not required to be present for a molecule to be
chiral !

The entire molecule can be chiral

(it can be its own stereocenter).

It doesn’t even matter whether there are any other

stereocenters present that we recognize as the usual
sources of chirality (including allenes, spiro rings, etc.)

A chiral molecule needs only to

have no symmetry of any kind.
 TESTING FOR CHIRALITY
The only definitive test for chirality is to take the
mirror image of the molecule and check if it will
superimpose :

chiral = mirror image doesnt superimpose

achiral = mirror image does superimpose

It doesn’t matter if you recognize any stereocenters

or not ! The entire molecule can be chiral !
 NOTE ALSO THAT

A compound can have stereocenters and not be chiral.

meso compounds are an example

COOH
Br
Br R
R OH
CH 3
S
H OH
CH 3 S
H COOH

STEREOCENTERS give a molecule the possibility of

being chiral, but they do not assure
it; a plane of symmetry is possible.
 Enantiomers and Physiological Activity

The handedness of the chiral herbicide metolachlor.

Drugs: Enantiomers Act Very Differently
O O

H2N R NH2
S
OH HO
H NH2
H2N H O
O

Bitter Sweet

Asparagine

Cl Cl
H3C H H CH3
HO OH
S O R
O

O Cl Cl O
Active Inactive
Dichlorprop
(Herbicide)

H OH HO H
H H
N CH2OH HOH2C N
S R

OH HO

Antagonist Bronchodilator

Albuterol
 Enantiomer Recognition
In nature: Enzymes, receptors

Synthetic: Enantiomerically pure reagents and catalysts

 Enantioselectivity:
Generating One Enantiomer from
Achiral Material

Which? A “handed”
reagent
or catalyst can
tell
the difference

Nevertheless, we still need a chiral auxiliary to generate a

new stereocenter selectively. What generated the “first”
enantiomer?
Amplification of Chirality from Extremely Low to Greater than 99.5% ee by
Asymmetric Autocatalysis
Itaru Sato, Hiroki Urabe, Saori Ishiguro,Takanori Shibata, and Kenso Soai*
Angew. Chem. Int. Ed. 2003, 42, 315