CH3
H
H2C
CH3
CH3
H
H3C
CH2
Stereoisomerism
Subtle Changes Create
Fragrant Differences
2
Enantiomers
Stereoisomers
Isomers
Diastereomers
Structural
Isomers
3
Chirality and Enantiomers
 Gloves
v. Socks
 Chiral


Exhibits handedness
Non-superimposable images in mirror test
 Achiral


Does not exhibit handedness
Identical or superimposable images in mirror
test
4
Enantiomers
A
pair of molecules related as
nonsuperimposable mirror images
 Look at 2-chloropropane


Chiral?
Superimposable mirror images?
 Now,


look at 2-chlorobutane
Superimposable mirror images?
Chiral?
5
Stereogenic Centers
C
atom with 4 different groups attached
to it
 Marked with an asterisk (*)
 Indicates existence of enantiomers
 Lacks plane of symmetry
6
Configurations and R-S
Convention
 Arrangement
of groups around
stereogenic center
 Enantniomers…opposite configurations
 Need for identifying each enantiomer

Cahn-Ingold-Prelog (CIP) system…otherwise
known as the R-S system
7
R-S Convention
 Four
groups attached to stereogenic
center are placed in priority order
(abcd)
 Stereogenic center is then observed from
the view point opposite the lowest priority
group, d


If remaining groups form clockwise array,
then it’s R
If counterclockwise, then it’s S
8
R-S Convention—Assigning Priority
of Groups
 Rule



1
Atoms directly attached to stereogenic C
are ranking according to At#...>At# =
higher priority
H always has lowest priority
If H is a group, then you’ll look down the
C-H bond to view the molecule, otherwise
look down the C-lowest priority bond
9
R-S Convention—Assigning Priority
of Groups
 Rule




2
Used if Rule 1 does not allow you to reach a
decision…two groups are identical
Work outward from the stereogenic center
until a decision is reached
Ethyl has higher priority than methyl
Saturated cyclic cpds follow same rules
10
R-S Convention—Assigning Priority
of Groups
 Rule



3
Required to handle unsaturated bonds and
aromatic rings
Multiple bonds are treated as if the atoms
involved bonded singly to each other
vinyl group, CH=CH2
CH CH2
C
C
11
E-Z Convention of Cis-Trans Isomers
 Eliminates
ambiguity
 Prioritize each group attached to doublebonded C, and do same for other C in
double bond
 E (entgegen)—if both higher priority
groups on opposite side of double bond
 Z (zusammen)—if high priority groups are
on same side of double bond
12
Polarized Light
13
Polarized Light and Optical
Activity
14
Polarized Light and Optical
Activity






= observed rotation depends on
Molecular structure
Concentration
Length of sample tube
Wavelength of light
Temperature
 Dextrorotatory
(+)
 Levorotatory ()
15
Calculating Specific
t
Rotation…[]
[] =
t


lxc
= observed rotation
 l = length of tube in dm
 c = concentration of soln in g/mL
 t = temperature of soln…usually RT (298K)
  = wavelength of light (typically 589.3 nm,
that of sodium vapor’s D-line )
16
What Makes a Molecule Optical
Active
 Achiral
molecules cancel polarity…
1 molecule rotates light in one direction,
while mirror image molecule rotates light
in opposite direction…cancelling activity
 Chiral molecule solns consisting of a single
type of enantiomer (R or S, but not both)
are optically active…a 1:1 mixture of R&S
enantiomers are known as racemic
mixtures and are optically inactive
17
Properties of Enantiomers
 Baseball



Ball
Bat
Glove
 Identical
achiral properties (mp, bp, D)
 Different chiral properties


Direction of rotation of plane –polarized
light
NOT degrees of rotation
18
Lactic Acid Enantiomers
(S)-(+)-lactic acid
[]
25°C
+3.33
D
(H2O)
mp = 53°C
(R)-()-lactic acid
[] 25D °C3.33 (H O)
2
mp = 53°C
19
Enantiomers in Biology
 Neither
R nor S dictates () or (+)
 Direction can determine rxn that will
occur



Lactic acid dehydrogenase reacts with (+)lactic acid to make pyruvic acid, but not
with ()-lactic acid
()-adrenalin, cardiac stimulant; (+)adrenalin is ineffective
One could be toxic, the other harmless
20
Fischer Projections





Replaces dashed and solid wedges to 2dimensions
Stereogenic C is intersection of horizontal and
vertical
Horizontal represent groups connected to
stereogenic C above (toward you) plane of
page
Vertical represent groups connected to
stereogenic C below (away from you) plane
of page
If lowest priority group is not on vertical arm,
rotate three of four groups to make it so
21
Fischer Projections
CO2H
H
OH
CH3
(R)-lactic acid
22
Compounds with More Than One
Stereogenic Center
 Biochemistry,
carbohydrate chemistry
 Consider 2-bromo-3-chlorobutane
2


stereogenic centers
Each center could be R or S
Four isomers: (2R,3R), (2S,3S), (2R,3S), (2S,3R)
23
Compounds with More Than One
Stereogenic Center
CH3
CH3
CH3
CH3
Br
C
H
H
C
Br
Br
C
H
H
C
Br
H
C
Cl
Cl
C
H
Cl
C
H
H
C
Cl
CH3
CH3
CH3
CH3
(2R,3R)
(2S,3S)
(2R,3S)
(2S,3R)
-2-bromo-3-chlorobutane suffix for all
Remember to rotate 3 of 4 groups to get lowest
priority on vertical axis
24
Compounds with More Than One
Stereogenic Center
 (2R,3R)
& (2S,3S) enantiomers
 (2R,3S) & (2S,3R) also enantiomers of each
other
 So, how are (2R,3R) & (2R,3S) related to
each other
CH3
CH3
Br
C
H
Br
C
H
H
C
Cl
Cl
C
H
CH3
CH3
25
Diastereomers
 (2R,3R)
& (2R,3S) are stereoisomers, but
not enantiomers
 Diastereomers—stereoisomers that are not
mirror images of each other


May differ in all properties, including achiral
properties…mp, bp, D, rotation, degrees of
rotation…could be everything
2 different cpds
26
Calculating Number of
Stereoisomers
 As
number of stereogenic centers (n)
increases, so does number of
stereoisomers
 Every time a stereogenic center is added,
R and S configurations are possible


Rule: 2n = number of stereoisomers
What is the maximum number of
enantiomers equation?
27
Meso Compouds
 Occur
when diastereomers are achiral
and therefore identical isomers
 Optically inactive due to achirality
 Consider 2,3-dichlorobutane
28
Meso Compounds
CH3
CH3
CH3
CH3
Cl
C
H
H
C
Cl
Cl
C
H
H
C
Cl
H
C
Cl
Cl
C
H
Cl
C
H
H
C
Cl
CH3
CH3
enantiomers, chiral
CH3
CH3
identical, achiral,
meso
29
Meso Compouds
 Plane
of symmetry
 Represent a single cpd
 Same 4 groups attached
 Superimposable mirror images
CH3
 Identical
 Achiral
C
Cl
Cl
C
CH3
CH3
H
H
C
Cl
H
H
C
Cl
CH3
30
A Research Project on Meso Cpds
and Racemic Mixtures
 Conduct
independent research on Louis
Pasteur’s work with tartaric acid.
 Learn all that you can about his work
 Be prepared to discuss such work on
examination
31
Stereroisomers
A
Conformers
B
Configurational
Isomers
Chiral
C
Achiral
Enantiomers
Diastereomers
32
Combinations of Stereoisomers
 Consider
cis-2-butene and trans-2-butene,
also known as Z-2-butene and E-2-butene
33
Combinations of Stereoisomers
 Consider
staggered and eclipsed ethane
34
Combinations of Stereoisomers
 Consider
acid
(R)-lactic acid and (S)-lactic
35
Combinations of Stereoisomers
 Consider
meso-tartaric acid and (R,R)tartaric acid
36
Stereochemistry and Rxns
 Achiral
reactants  chiral product (both
enantiomers are formed at equal rates
and in equal concentrations—racemic
mixture)
 Chiral and achiral reactants  new
stereogenic center (diastereomers,
different rates, different concentrations)
37
Achiral Reactants  Chiral
Product
 Write
the rxn of 1-butene with
HBr…remember Markovnikov’s Rule
38
Achiral Reactants  Chiral
Product
+
Br -
CH3CH2CH=CH2 + H+  CH3CH2CHCH3 
2-butyl cation
CH3CH2CHCH3
Br
39
Achiral Reactants  Chiral
Product
(S)-2-bromobutane
H
CH3CH2—C
Br -
CH3
Br
C H
CH3CH2 CH3
(R)-2-bromobutane
CH3CH2
H
C CH3
Br
40
Achiral Reactant + Chiral
Reactant 
 Write
HBr.
+
the rxn of 3-chloro-1-butene with
CH3CHCH=CH2 + HBr 
Cl
41
Achiral Reactant + Chiral
Reactant 
CH3
Cl
R
C
CH3
H
CH
CH2
(R)-3-chloro-1-butene
HBr
Cl
H
R
C
R
C
CH3
H
Br
+
CH3
(2R,3R)-2-bromo-3-chlorobutane
Cl
Br
R
S
C
H
C
H
CH3
(2S,3R)-2-bromo-3-chlorobutane
The Cl group remains R; the new stereogenic center can be
either R or S.
42
Resolving Racemic Mixtures
 Separation
of racemic mixture’s
enantiomers is resolution

Convert to diastereomers
 By
letting enantiomers react w/chiral reagent
 Pasteur was 1st to resolve racemic mixture

Convert separate diastereomers back to
enantiomers
 Same
concept as specificity in biological
rxns—enzymes usually chiral reagent