CHM 136 H
Stereochemistry
Chapter 5 excluding 5.3, 5.4, 5.10, 5.12
Chapter 25: 25.2 only
McMurry, 9th edition
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Chapter 7: 7.4, 7.5
Isomers
Different compounds with the same molecular formula
Constitutional isomers:
isomers with different
atomic connectivities
Stereoisomers: isomers
with the same atomic
connectivity but with
different geometries
O
OH
H
Br
H
Br
H
Br
Br
H
2
1
2
McMurry 9th Ed., Section 7.5
Di-substituted alkenes can be named cis or trans:
Cahn-Ingold-Prelog rules for naming alkenes
First, a brief look at alkene stereochemistry
cis trans
We need rules for naming
tri- and tetra-substituted alkenes
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Tri- and tetra-substituted alkenes
Two stereoisomers:
Z: the two groups of higher priority are on
the same side of the double bond
E: the two groups of higher priority are on
the opposite side of the double bond
We determine priority with the Cahn-Ingold-Prelog rules
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3
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The Cahn-Ingold-Prelog rules
1. Rank atoms on each end of the double
bond in decreasing atomic number
Br > Cl > F > O > N > C … > H
2. If the first atoms in the substituent are the
same, look at the 2nd, the 3rd, the 4th, ….,
until the first difference is found
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3. Multiple-bonded atoms are equivalent to same number
of single bonded atoms
E.g. when you see: prioritize using:
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mirror
The mirror image:
Chirality = "handedness"
objects that do not have a
mirror plane are CHIRAL
objects that contain a
mirror plane are ACHIRAL
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Properties of chiral objects
A chiral object and its mirror image
cannot be superimposed
achiral: can be superimposed
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chiral: cannot be superimposed
Molecules that possess a mirror plane are ACHIRAL.
mirror plane
Some molecules are achiral, some are chiral:
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Chiral molecules cannot be superimposed on their mirror image
Some molecules are achiral, some are chiral:
A chiral molecule:
mirror plane
Some molecules are achiral, some are chiral:
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Which are chiral and which are achiral?
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Chiral molecules and their non-superimposable
mirror images are called “enantiomers”
chiral
enantiomers
The chirality often originates from a tetrahedral carbon atom that is
bonded to four different substituents. Such a carbon centre is called a
"chirality centre" or "stereocentre"
chirality centre
13Molecules with odd numbers of chirality centres are chiral.
Biology is full of chiral molecules
alanine:
sucrose (table sugar):
chiral
chiral
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Which of the following drugs is/are chiral?
Where are the chirality centres?
Aspirin Tylenol Advil
(acetaminophen) (ibuprofen)
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melting point:
So how can enantiomers be differentiated from each other?
2. optical activity
1. interactions with other chiral molecules/environments
−112 °C 91 °C 1.255 g/mL
S R
e.g. 2-bromobutane
density:boiling point:
Enantiomers have identical physical properties
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1. interactions with other chiral molecules/environments
E.g. many biological receptor sites are chiral – will only
“accept” one particular enantiomer of a substance
- biological molecules often have
different tastes, smells, toxicities
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(+)-carvone
smells like
caraway
(-)-carvone
smells like
spearmint
2. optical activity
chiral molecules are
optically active –
they rotate
plane-polarized light
one enantiomer rotates light to
the right = (+) or d-enantiomer
other enantiomer rotates light to
the left = (−) or l-enantiomer
(S)-(+)-lactic acid (R)-(–)-lactic acid
observeranalyzerpolarizer sample tube
light
source
unpolarized
light
polarized
light

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- optically active compounds must be chiral:
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one enantiomer rotates light to
the right = (+) or d-enantiomer
other enantiomer rotates light to
the left = (−) or l-enantiomer
(S)-(+)-lactic acid (R)-(–)-lactic acid
- equal concentrations of enantiomers will rotate light in opposite
directions by the same amount:
e.g. 1.00 g/mL (R)-(−)-lactic acid:  = −3.82°
1.00 g/mL (S)-(+)-lactic acid:  = +3.82°
1.00 g/mL (S)-2-bromobutane:  = +23.1°
1.00 g/mL 2-bromo-2-methylbutane:  = 0.0°
Indicating chirality
- how to indicate the different configuration of substituents
around each chirality centre?
1. Identify the chirality centre
lactic acid
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2. Determine the priorities of
attached groups
3. Rotate molecule to put the
lowest priority group at the back
H at the back behind C
the Cahn-Ingold-Prelog rules
left hand turn
(anti-clockwise)
lactic acid
Its enantiomer:
(S)-
1
2
3
right hand turn
(clockwise)
“R” and “S” are the (absolute) configurations of a chirality centre
4. Determine direction from 1st to 2nd to 3rd priority groups
2
1
3
lactic acid(R)-
Easy to remember! R = "right"
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REVIEW: determining group priorities: the Cahn-Ingold-Prelog rules
2. If the first atoms in the group are the same,
look at the 2nd, the 3rd, the 4th ….,
1. Rank atoms attached to the chirality centre
in decreasing atomic number:
Br > Cl > F > O > N > C … > H
3. Multiple-bonded atoms equivalent to same number of single
bonded atoms
When you see: prioritize using:
When you see: prioritize using:
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Let's try some examples
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Assign absolute configuration to the chirality centres in the
following molecules.
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Artemisinin (anti-malaria drug)
2015 Nobel Prize in Physiology or Medicine
R
R
S
R SS
R
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both C2 and C3 can be either R or S
threonine
Molecules with >1 chirality centre
For n chirality centres, a maximum of 2n stereoisomers exist.
2 3
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- two stereocentres
Four stereoisomers are possible:
2R,3R 2R,3S 2S,3R 2S,3S
e.g. (2S,3R)-2-amino-3-hydroxybutanoic acid
- configuration is given in parentheses at the front of the name:
S SR R
SR SR
The four possible stereoisomers
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enantiomers – must have opposite
configuration at ALL chirality centres
Non superimposable mirror images
diastereomers - configuration not
opposite at all chirality centres
NOT mirror images!
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D-glucoseD-galactose
R
Diastereomers have different physical and chemical properties
e.g. boiling point, spectra, solubility, etc.....
R
S S
m.p. = 167oC m.p. = 146oC
R
R
R S
D-mannose
m.p. = 133oC
S
R
R S
E.g. tartaric acid
= meso compound
A molecule can have chirality centres but still be achiral
RS
RS
meso compounds have
an internal mirror plane
RS
The molecule and its mirror image are superimposable = achiral
RRSS
Its other two stereoisomers
are enantiomers
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Fischer projections (Section 25.2)
Fischer represented chirality centres differently:
Fischer
projection
1852-1919
Emil Fischer
the molecule
appears flat
central C atom
is not shown
horizontal lines
out of the page
vertical lines
into the page
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- two (or more) chirality centres:
R,R-tartaric acid
normally, the longest
carbon chain is
drawn vertically
R
R
COOH
COOH
OH
HO H
Hrotate
the vertical line connecting the two middle
chirality centres lies in the plane of the page
all other vertical lines go into the page
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Fischer projections can be rotated according to certain rules
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180o
same as
keeping one group fixed
and rotating the others
How are Fischer projections useful?
- helpful for visualizing molecules with
two or more chirality centres
e.g. sugars and sugar derivatives
CH=O
OH
OH
OH
HO
H
H
H
H
CH2OH
by convention, the carbon with the
higher oxidation state is put at the top
D-glucose
COOH
COOH
OH
HO H
H
- it is easy to draw mirror images COOH
COOH
H
H OH
HO
R,R
tartaric acid
S,S
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Practice
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Draw Fischer projections of all of the isomers of 2,3-dichlorobutane.
What is the relationship between the isomers?
Prochirality
An achiral molecule is prochiral if, in a single chemical step,
it can be converted into a chiral product.
H2
2-butanone 2-butanol
prochiral chiral
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H2
Stereochemical result of prochirality
2-butanone
prochiral
and
clockwise = re face
counterclockwise = si face
racemic mixture!
Trigonal planar atoms can have prochiral faces:
or
si face
re face
H
H
Stereochemical Result of Prochirality
(S)-2-Butanol
(R)-2-Butanol
“re” and “si” refer to the reactant, NOT the product!!
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Defining pro-R and pro-S substituents:
1. Raise the priority of the atom of interest over the other (identical)
atom without changing the priority relative to the other
substituents
2. Use the usual method to determine the configuration of the
chirality center
prochiral centre
" "
" "
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3 4
Tetrahedral atoms can be prochiral centres:
Practice
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Label the relevant hydrogen atoms in sec-butanol as pro-R and pro-S.
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Summary isomersconstitutional
Isomers
different connectivity
Enantiomers
Non superimposable
mirror images
same connectivity
stereoisomers
Diastereomers
Non superimposable
non mirror images
cis - trans
diastereomers
(E/Z)
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meso compounds
Superimposable mirror images
RS
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