Module F Naming enantiomers

 Enantiomers are different molecules with different properties,

Stereoisomers so they should have different names
Based on Bruice’s Organic Chemistry: Chapter 4  The two mirror image lactic acids should have different names

Learning Outcomes: By the end of this module, you will learn:

1. How to assign the configurations of stereocenters
2. What are diastereomers and meso compounds
3. How to resolve a racemic mixture
4. How to classify stereoisomers  (+)- or (−)- labels can only be used after we measure the optical rotation
5. How to assign the configurations of alkene double bonds
 But we do not want to have to measure optical activity every time we want
to name an enantiomer
1 2

Naming Enantiomers The Cahn-Ingold-Prelog (CIP) Convention

 1. Assign priorities to the four groups around the
 It would be more useful and convenient stereocenter, according to atomic number
to derive names and labels for  Eg.
stereocenters which is related to the
structure
 The configuration is the relative
positions of all substituents with
respect to each other at the
stereocenter
 We need a method to specify the
configuration of a stereocenter
3 4
 The Cahn-Ingold-Prelog (CIP) Convention The Cahn-Ingold-Prelog (CIP) Convention
 1. Assign priorities to the four groups around  2. Orient molecule so the lowest priority group is pointing
carbon by atomic number to the back.

2 2 1
2
1 4
4
1

3 3

3
5
6

The Cahn-Ingold-Prelog (CIP) Convention The Cahn-Ingold-Prelog (CIP) Convention

 3. Assigning the configuration:

Point thumb to the back
(to the lowest priority group)
1 1
4 4

2 3 3 2

If the priorities of the 3 If it corresponds to a

remaining groups correspond right hand (ie.
to left hand's turn (ie. anti- clockwise), it is R.
clockwise), it is S. Left Hand Right Hand

“Sinister” “Rectus”
7 8
 The Cahn-Ingold-Prelog (CIP) Convention CIP Rules: Extended Comparison (1)
 Q: What is the stereochemistry of this 2-bromobutane?
 The complete IUPAC name of this  In assigning priorities, if atomic numbers are the same, compare at
molecule is: the next set of bond connections, at the FIRST point of difference
2 1
(S)-bromochloroiodomethane

 Its enantiomer, a different

compound, has a different name:
3
(R)-bromochloroiodomethane”

Corresponds to left-hand
turn: S-configuration

9 10

CIP Rules: Extended Comparison (1) CIP Rules: Extended Comparison (1)

O (H ) O (C ) C (N, C, H) C (Cl, H, H )
C (H, H, H) C (C, H, H) C (C, C, H) C (C, H, H )
LOWER HIGHER LOWER HIGHER
LOWER HIGHER HIGHER LOWER

11 12
CIP Rules: Extended Comparison (1) CIP Rules: Extended Comparison (1)

1 1
1
1
3
2
2
2 2
3 4
3 4

4 3

 From the view with lowest priority bond

 This is (S)-2-bromobutane pointing towards us, this is a right hand turn
 So from the view looking down at C-4, it
13 would be the opposite, so it is (S) 14

CIP Rules: Extended Comparison (2)

CIP Rules: Extended Comparison (3)
Multiple bonds:
 A difficult comparison:
 Double bonds count as 2 bonds to identical atoms
 Triple bonds count as 3 bonds to identical atoms

C (O, O, C) C (O, O, C)
O (C), and O (C) O (C), and O (C) back to sp2-C
O, O, H O, O, H C (C, H, H) and C (C, H, H) C (0, 0, 0) Bonds not compared twice-
considered to be bonded to priority 0
HIGHER LOWER
15 16
 Another Example
The Cahn-Ingold-Prelog (CIP) Convention
 Serine is an amino acid first isolated from silk protein.
Which enantiomer is this one?  1. Assign substituent
1
priorities:

4  -NH2 has first priority

because N has higher
atomic no. than C or H
 -H has lower priority

Pause the video to do this exercise.

17 18

The Cahn-Ingold-Prelog (CIP) Convention The Cahn-Ingold-Prelog (CIP) Convention

 2. Orient molecule so the lowest priority group is pointing to the back.

 The other two groups are both

1
C, so we have to look at the 3 1
next point of difference
4 3
 This C bonded to O, H, H
2 2
 This C bonded to O, O, O
higher priority
 Corresponds to right-hand turn
 “(R)-serine”: this is the unnatural amino acid
19 20
Stereocenters at Atoms other than Carbon Stereocenters at Atoms other than Carbon
 Tetravalent nitrogen and phosphorus can be chiral  Trivalent nitrogen is tetrahedral and is chiral
 However, its configuration not stable so it is useless to determine it,
usually not assigned

https://www.youtube.com/watch?v=O-AD9I8c-GI
21 22

2-57

Stereocenters at Atoms other than Carbon Exercises

 You should be
 Chiral trivalent phosphorus inverts more slowly and is configurationally able to assign R
stable, and it is meaningful and expected to assign its configuration or S for each
stereocenter for
Lowest priority for lone pair electrons, even lower priority a molecule
than hydrogen
shown in any
representation
3 2 2 3  How quickly and
accurately can
you make the
assignments? Pause the video to complete this exercise
23 24
 Solutions No Correspondence to Optical Rotation
 The sign of optical rotation (+)- or (−)- has NO correspondence
to (R)- or (S)-configuration

25 26

Module F Compounds with Two or More Stereocenters

Stereoisomers  This is a
compound whose
Based on Bruice’s Organic Chemistry: Chapter 4 common name is
threonine, and its
IUPAC name is
2R, 3R 2S, 3S 2R, 3S 2S, 3R
2-amino-3-
Learning Outcomes: By the end of this module, you will learn:
hydroxybutanoic Diastereomers:
1. How to assign the configurations of stereocenters acid Stereoisomers
that are
2. What are diastereomers and meso compounds  Each not mirror
3. How to resolve a racemic mixture stereocenter images

4. How to classify stereoisomers should be

5. How to assign the configurations of alkene double bonds assigned as R or
S configuration
27 28
Compounds with Two or More Stereocenters Enantiomers and Diastereomers
2-Amino-3-hydroxybutanoic acid
 Enantiomers differ in optical activity, but otherwise their
physical properties are the same
 Eg. mp, bp, solubility, NMR, IR spectra, ….
 Diastereomers have different properties

Diastereomers: Stereoisomer mp pK []D

Stereoisomers
that are (2S,3R)-2-Amino-3-hydroxybutanoic acid 255 °C 9.24 28.4 °
not mirror
images
(2R,3S)-2-Amino-3-hydroxybutanoic acid 255 °C 9.24 +28.5 °
Moodle Stereochemistry drill for practice
(2S,3S)-2-Amino-3-hydroxybutanoic acid 273 °C 9.07 +8.7 °

29 30

Number of stereocenters and Number of stereocenters and

possible stereoisomers possible stereoisomers
 If n= number of stereocenters in a molecule, 2n is  Molecules with 2
the maximum number of stereoisomers possible stereocenters have
maximum of 22= 4
isomers, where the
Molecules with one configuration of
stereocenter can have 21= each stereocenter
2 isomers; in this case, can be specified as
two enantiomers of serine R or S

31 32
 Number of stereocenters Number of stereocenters and
and possible stereoisomers possible stereoisomers
 Not all molecules with 2 stereocenters have 4 stereoisomers  Having an internal plane of
 Eg. tartaric acid symmetry, the two apparent
enantiomers are actually identical

This isomer has a plane of

symmetry: achiral molecule
33 34

Meso Compounds Meso Compounds

 For tartaric acid, one diastereomer is chiral: two enantiomeric forms
 A meso compound has stereocenters but also a plane of
 The other diastereomer has two stereocenters but is achiral —we
called this a meso compound
symmetry, so it is achiral
 Thus having stereocenters is not a guarantee of chirality

Chiral Achiral —Meso compound

A total of 2 + 1 = 3 stereoisomers of tartaric acid exist.

35 36
 Meso Compounds Module F

 Meso compounds are diastereomers of (+)- or ()-enantiomers, so Stereoisomers

they have a completely different set of physical properties
Based on Bruice’s Organic Chemistry: Chapter 4

Learning Outcomes: By the end of this module, you will learn:

1. How to assign the configurations of stereocenters
2. What are diastereomers and meso compounds
3. How to resolve a racemic mixture
4. How to classify stereoisomers
5. How to assign the configurations of alkene double bonds

37 38

Racemic Mixtures and Resolution

Manual Resolution is not General
 A 50:50 mixture of two enantiomers is called a racemic mixture
or a racemate
 A racemic mixture is NOT optically active
 The equal and opposite rotations cancel each other out
 Eg. Paratartaric acid is a racemic mixture: contains 50% (+) -tartaric acid
and 50% (-)-tartaric acid
 The separation of the enantiomers of a racemic mixture is
called resolution
 Pasteur resolved (±)-tartaric acid crystals manually
 Not all compounds solidify into enantiomeric crystals! So this not a
general method of resolution

39 40
 Resolution of Racemic Mixtures Resolution of Racemic Mixtures
 Another method of resolution is to convert them to diastereomers
 A more general which can be separated, then converted back to the original molecules
method of resolution
Chiral
is to convert the
Achiral
racemate to
diastereomers which
can be separated, then
Same properties
convert them back to
Same solubility, (R)-1-phenylethylamine
the original molecules crystallization… has the role of a
resolving agent Different properties
 An achiral reagent cannot be
Separable
separated
cannot be used

41 42

Enantiomeric excess (ee) Module F

 A measure of enantiomeric purity Stereoisomers

 Defines how much of an excess of one enantiomer is in a Based on Bruice’s Organic Chemistry: Chapter 4
mixture

Learning Outcomes: By the end of this module, you will learn:

1. How to assign the configurations of stereocenters
2. What are diastereomers and meso compounds
3. How to resolve a racemic mixture
4. How to classify stereoisomers
5. How to assign the configurations of alkene double bonds

43 44
 A Review of Isomerism Constitutional Isomers
 Types of isomers:
 Different bond connections gives different carbon
backbone and/or different functional groups

A good clue is that the

IUPAC names are different

45 46

Stereoisomers Conformations vs. Configurations

 Same dog in different poses  Different dogs!

 Molecules with the same bond connections, but

different spatial arrangement of atoms

 Classified with respect to stability towards

interconversion (and therefore if they are separable):
 Different cyclohexanes! Different
 Conformational isomers vs configurational Isomers  Same cyclohexane, in different conformations configurational stereoisomers!
 Do not confuse these terms!

 To change from one configuration to

another, bonds have to be broken
47 48
 Stereoisomers Stereoisomers
 Molecules with the same bond connections, but different  Stereoisomers that are related as non-superimposable mirror
spatial arrangement of atoms images: enantiomers
 All other stereoisomers are diastereomers
 Classified with respect to structural relationships

49 50

Stereoisomers Module F

 Diastereomers are molecules with the same bond connections, but

different spatial arrangement of atoms that are not related as mirror Stereoisomers
images
 Includes cis, trans, and configurational (R/S) isomers
Based on Bruice’s Organic Chemistry: Chapter 4
CO2H
H NH2
H OH
Learning Outcomes: By the end of this module, you will learn:
CH3
1. How to assign the configurations of stereocenters
2. What are diastereomers and meso compounds
3. How to resolve a racemic mixture
Cis, trans
diastereomers
4. How to classify stereoisomers
5. How to assign the configurations of alkene double bonds

51 52
 Stereoisomerism in Alkenes Stereoisomerism in Alkenes
Alkane C-C bonds Alkene C=C bonds  The barrier for rotation of a carbon-carbon double bond creates the
possibility of isomers
 Alkene stereoisomers are also called geometric isomers, a kind of
diastereomer
 For disubstituted alkenes:
 A cis isomer - two protons on same side of the double bond
 A trans isomer – two protons on opposite sides of the double bond

 Alkenes have double bonds made of a -bond and a -bond

 Unlike alkanes, alkenes have  bonds that prevent rotation about -bond
 Rotation energy barrier = ~ 268 kJ/mol for ethene
 Recall that it was just 12 kJ/mol for ethane! 53 54

Stereoisomerism in Alkenes Geometric Isomers of Other Alkenes

 Cis, trans nomenclature
can only be used for
disubstituted double bonds
 Geometric isomers of
trisubstituted and
tetrasubstituted alkenes
 Cis- , trans-alkene isomers are NOT
cannot be named “cis” or
interconverted by a rotation, it would
“trans”
require breaking of the  bond
 Conversion can occur by bond breaking
and making, under strong heating, or
irradiation with light
55 56
 IUPAC E,Z System of Nomenclature Cahn-Ingold-Prelog Rules
 For each sp2-carbon of the double bond, assign priority to the two  Example:
substituents according to the Cahn-Ingold-Prelog (CIP) rules High priority groups on the same side of
L L the double bond
 Then, assign double bond configuration as Z or E:

H H This is a (Z)- alkene. Full IUPAC name is

“(Z)-2-Bromo-1-chloroprop-1-ene”

 The other CIP rules also apply:

 If atomic numbers are the same, compare at the next bond
connection, at the FIRST point of difference
 Double bonds count as 2 bonds to identical atoms
E -entgegen, opposite sides
Z - zusammen, on the same side  Triple bonds count as 3 bonds to identical atoms
57 58

CIP Rules: Extended Comparison Additional Examples

Lower
Higher C
CH2CH3  These can be named using cis/trans or
E/Z
HC C
C C H  But E/Z is used in IUPAC nomenclature
Higher
C C
HOH2C O  Cis/trans ring compounds can also be
Lower named using R/S to specify the
 C is bonded to (C, C) configuration of the stereocenters
 Next point of difference: C (C, H, H) vs. C (C, C, C)
 Some cyclic diastereomers cannot be
 C is bonded to (C, C) named using cis/trans; R/S must be
 Next point of difference: C (O, O, H) vs. C (O, H, H) used
 E/Z, R/S to designate configuration is
This is an (E)-alkene. 59 more generally applicable 60
 Additional Examples Exercise
 Suppose you are the only chemist in a team doing a project in an
outpost in Siberia. Communication in and out can only be by phone.
You need to order the following compounds as reference standards,
by giving their correct, unambiguous IUPAC names to Acme
Chemicals UK.

 D has higher priority than H

 First comparison, both are C(CCH)
 First point of difference C(HHH) vs C(CHH)
Pause the video to complete this exercise.
 This is the (Z)-isomer
61 62

Exercise Exercise
 Answers:  Draw, then give the full IUPAC names all of the double
bond isomers of 1-chloro-2,4-heptadiene.
 How many stereoisomers are possible?
(E)-3-methylhexa-1,3-diene

Pause the video to complete this exercise.

(2Z,4E)-5-bromo-2-methylpenta-2,4-dien-1-ol

(2E,4Z)-5-bromo-2-methylpenta-2,4-dien-1-ol is a different compound!

63 64
 Module F
Exercise
Stereoisomers
 Answers: Based on Bruice’s Organic Chemistry: Chapter 4

Check that you have achieved these learning outcomes, and can
give examples to explain and answer each of these questions:

1. How to assign the configurations of stereocenters

2. What different kinds of stereoisomers exist
3. How to resolve a racemic mixture
4. What diastereomers of alkenes exist

65 66

Summary of Chapter 4 Concepts: Summary of Chapter 4 Concepts:

Chiral molecules & Stereocenters Enantiomers
 Molecules that have two non-superimposable mirror image
 Enantiomers have the same chemical and
isomeric forms are chiral molecules physical properties
 The two mirror-image isomers are called “enantiomers” Except:
 Chiral molecules do not have internal symmetry  Interaction with plane polarized light: optical activity
 Stereocenters are atoms with 4 different substituents  Interactions and reactions with other chiral entities,
 The configuration of each stereocenter is named R or S using CIP eg. chiral reagents, living organisms
rules  Purity is expressed by enantiomeric excess (ee)
 Stereocenters do not guarantee chirality: eg. meso compounds

67 68
 Summary of Chapter 4 Concepts: Summary of Chapter 4 Concepts:
Optical Activity Optical Activity
 If a homogeneous sample shows no optical activity, the
 Optical activity is the ability to rotate plane-polarized light possibilities are:
 Enantiomers are optically active  It is an achiral compound
 A pair of enantiomers rotate polarized light in equal and opposite  It is a racemic mixture of a chiral compound
directions  If a homogeneous sample shows optical activity, the
 Achiral compounds are optically inactive possibilities are:
 Racemic mixtures are optically inactive  It is a pure sample of a chiral compound
 A non-racemic mixture (ee > 0) is optically active  It is a mixture of enantiomers of a chiral compound in which
one enantiomer is in excess: ee > 0

69 70

Major Topics of Chapter 4 After studing Chapter 4, you should be able to:
 Fischer projections
 Recognize and understand the implications of chirality and
 Chirality enantiomerism
 Enantiomers and their properties  Draw enantiomers and diastereomers as perspective drawings or
 Diastereomers and their properties Fischer projections
 Assign the configuration of any stereochemical elements by (R, S)
 Meso compounds and (E, Z), for molecules presented as any molecular representation
 Optical activity  As skeletal structures, Fischer and Newman projections, chairs, etc.
 Resolution
 Assigning stereocenter configurations- R or S
 Assigning double bond configurations- E or Z Towards Course Learning Outcomes 1 and 2

71 72