CH264 Mechanism and Stereochemistry Lecture 1 Undergraduate Year 2 module on shape and reactivity of mostly organic molecules.

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CH264/1
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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