The document outlines the principles of stereochemistry in organic chemistry, focusing on Cahn-Ingold-Prelog rules for stereochemical assignments, differentiation between enantiomers and diastereomers, and the concept of chiral molecules without stereogenic centers. It highlights mechanisms for assigning stereochemistry, the uniqueness of diastereomers, and the properties of meso compounds, along with prochiral and stereogenic centers. Key concepts such as optical activity, axial and helical chirality, and examples of chiral molecules are also discussed.

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Organic Chemistry II
Mechanism and
Stereochemistry
Dr Andrew Marsh C515
a.marsh@warwick.ac.uk
Dr David J Fox B510
d.j.fox@warwick.ac.uk

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Today’s Lecture
1. Cahn-Ingold-Prelog rules for stereochemical assignment
2. Enantiomers - molecules with one stereogenic centre
3. Diastereomers - molecules with two or more stereogenic
centres
4. Chiral molecules without a stereogenic centre
CGW = Organic Chemistry J Clayden, N Greeves, S Warren 2nd
Edition OUP 2012

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Molecular shape and asymmetry
O O
mirror plane
spearmint caraway seed
(-)-carvone (+)-carvone
N
NH
O
O
O
O H
S-thalidomide
N
N H
O
O
O
OH
mirror plane R-thalidomide
sedative, hypnotic teratogenic
anti-abortive
pp. 302 – 311 CGW 2/e
H
H Cl
Br
H
HCl
Br
mirror plane rotate 180°
H
H Br
Cl
IDENTICAL
H
H Cl
Br
rotate 180°

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Optical Activity
pp. 309 CGW 2/e
polariser
analyser (polarising filter)polarised light
(electric field oscillating
in one direction only)
view
optically active compound
in solvent
monochromatic
light source

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Assignment of stereochemistry
• If an atom has four different groups around it, the centre is
STEREOGENIC and the molecule will be CHIRAL
• Cahn-Ingold-Prelog sequence rules (C-I-P) are used to
assign stereochemistry to that centre
• Revision: CGW p.308
If we assign a PRIORITY to these groups such that a>b>c>d and then re-draw the
molecule such that the lowest priority (d) points away from us:
a
c
b
d
re-draw a
bc
R stereochemistry

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C-I-P Assigning Priority
• We assign priority to the groups around the central atom according to atomic
number
Br
H
F
Cl
Br
H
F
Cl
view
direction
mirror
Br
FCl
anticlockwise = S
Br
ClF
clockwise = R
view
direction

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Assigning Priority 2
• Functional groups containing the same atom, look to the next
substituent to decide priority. e.g. butan-2-ol
• Use ‘single bond equivalents’ to decide which group takes priority.
For example, a carbonyl group = 2 C-O bonds, an alkene = 2 C-C.
HO
H
CH2CH3
H3C
OH
H
CH2CH3
CH3
view
direction
mirror
OH
CH2CH3H3C
OH
CH3H3CH2C
view
direction
R S
1
23
1
2 3

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Diastereomers
• Chiral molecules with two stereogenic centres are called
diastereomers. Diastereomers have different physical properties such
as m.p., b.p. solubility etc. Hence they are separable by standard
purification techniques, unlike enantiomers.
• Certain pairs of diastereomers can be mirror images of each other
and are thus enantiomers.
• Consider the reaction of butan-2-ol with 2 chloropropanoic acid.....
Me
OHEt
*
Me
Cl
HO
O
*+
Et
Me
O
O
Me
Cl
H+
CGW p. 311-315

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Et
Me
O
O
Me
Cl
Et
Me
O
O
Me
Cl
R, S R, R
Et
Me
O
O
Me
Cl
S, S
Et
Me
O
O
Me
Cl
S, R
enantiomers
diastereomers
diastereomers
diastereomersdiastereomers
CGW p. 315

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meso-Compounds
If a molecule has any symmetry element e.g. internal plane of symmetry, σ or
centre of inversion, i, it is rendered optically inactive and is designated meso-.
centre of inversion
CO2HHO2C
OHHO
meso-tartaric acid
CO2HHO2C
HO OH
CO2HHO2C
HO OH
(–)-tartaric acid(+)-tartaric acid
HO2C
CO2H
OH
OH
HO2C
CO2H
OH
OH
R
R S
S
S
R
HO2C
CO2H
OH
OH
m.p. 206°m.p. 168-170°m.p. 168-170°
[α]D = +12° (water, 20°C) [α]D = –12° (water, 20°C) [α]D = 0° (water, 20°C)

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Examples
CH3
OH
H
Br
F
Cl
Mark stereogenic centres with *
Classify R or S
Br
CH3
OHC
Br
CO2H
H

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Molecules without a stereogenic
carbon atom
Many atoms are stereochemically well-defined and thus can be considered as
stereogenic. Examples include sulfur and phosphorous.
DiPAMP - an enantiopure hydrogenation catalyst R-methylphenyl sulfoxide

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Chiral molecules without a
stereogenic centre
ALLENES - axial chirality since the
double bonds are hybridised at 90°
Biphenyls exhibit ATROPISOMERISM
If C-C rotation is restricted
CGW p. 319

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Helical Chirality
Examples of helical molecules include hexahelicene which can be resolved into two
enantiomers. When viewed from above, the right handed helix is described as P (plus) and
the left handed helix is called M (minus).

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Enantio/ diasterotopicity
A PROCHIRAL centre is one that can become stereogenic if one group is replaced by a
new, different one:
Ha and Hb are HETEROTOPIC and can be assigned C-I-P prochirality descriptors
H3C
O
OH
Ha Hb
H3C
O
OH
HO Hb
transformation
R-lactic acidpropionic acid
CGW p. 820-823

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Classification of prochiral centres
We simply use an extension of the Cahn-Ingold-Prelog rules for stereochemical
nomenclature to designate the heterotopic atoms pro-R or pro-S. We choose each of
the two atoms in turn giving it higher priority (1
H becomes 2
H for example) than the other
and carry out the usual C-I-P ranking procedure:
H3C
O
OH
Ha Hb
propionic acid
Ha
H3C
O
OH
Ha > Hb
Hb
CH3
O
HO
pro-R
pro-S
Hb > Ha

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Enantiotopic/ Diastereotopic Faces
R1
O
R2
NuNu
OH
R2
R1
Nu
OH
R2
R1
Nu
R1 > R2
Re-face attack
R2 > R1
Si-face attack
X
Y Z
If X>Y>Z front as viewed is Re-

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Examples
HO F
Ha Hb O
H3C
Cl
N
CH3
CH3
HO

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You should be able to:
(i) Use R/S configuration according to C-I-P nomenclature.
(ii) Define and use the terms enantiomer and diastereomer.
(iii) Recognise non-carbon atom stereogenic centres.
(iv) Define axial and helical chirality and give examples.
(v) Identify and use prochiral centres and faces.
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