CHAPTER 5: STEREOISOMERISM
 Isomers: different compounds with same formula
 Constitutional isomers: different constitution
(order of connectivity of atoms)
 Stereoisomers: same constitution but different
spatial arrangement of atoms
 To maintain overlap in pi bond, C=C bonds cannot
freely rotate; cis and trans different compounds
o There are also types of stereoisomerism
besides cis and trans
CHIRALITY
 Chiral object: asymmetric, which means not same
(not superimposable) on mirror image
o Mirror images of chiral molecules have
many identical properties, but not
identical, so pharmacology can be different
o Carbon bonded to 4 unique groups of
atoms is a chirality centre
 Cahn-Ingold-Prelog system: designate each
chirality centre as having either “R” or S”
configuration
o 1. Using atomic numbers, prioritize 4
groups attached based on highest
 Look at atoms one layer at a time
(atoms bonded to next atom,
organized by highest atomic)
 Double bonds count as two single
bonds (so if aldehyde, then list for
the C is O,O,H)
o 2. Arrange molecule in space so lowest
priority group faces away
 Switching two groups will produce
opposite configuration, so switch
back afterward
 Switching two groups returns to
original configuration
o 3. Count group priorities from 1-3 to
determine whether CW or CCW
o 4. CW = R and CCW = S
ENANTIOMERS
 Enantiomers: stereoisomers that are mirror images
of each other but not superimposable
o One way to draw enantiomer of chiral
compound is invert dashes and wedges of
a chirality centre
 Only a chiral compound can have enantiomer
o Enantiomer will have opposite
configuration at chirality centres
 Enantiomers have same physical properties but
differ in (a) how they interact with other chiral
compounds and (b) optical activity
 Plane-polarized light: light  polarizer (filter) 
electromagnetic waves travel in only one plane
 Optical active: compounds that rotate the plane of
plane-polarized light
o Polarimeter tube and chiral compounds
will rotate
 Degree to which rotated depends on sample
concentration and pathlength of the light
o Specific rotation: observed rotation under
standard conditions of 1g/mL, 1dm, unique
to each compound
o [] = /c*l
  is observed rotation, c is
concentration in g/mL, l is
pathlength in decimeters
o Will also be affected by temperature and
wavelength of light, so reported as []T
o (+) rotation is dextrorotary, (-) is levorotary
 No direct relationship between (+)/(-) and R/S
because the former is dependent on conditions
while the latter is not
o E.g. same compound can rotate (-) at some
temperature but (+) at another
o Therefore magnitude and direction of
optical rotation determined experimentally
 Enantiomers rotate to equal degrees but in
opposite directions
o Racemic mixture: 50/50 mixture of two
enantiomers
 Optical rotation cancels out, so
overall rotation is 0 degrees
o If one enantiomer present in excess, then
there will be optical rotation but less than
the pure enantiomer
 Enantiomeric excess (ee)
 %ee = |observed |/| of pure
enantiomer| * 100%
DIASTEREOMERS
 Diastereomers: stereoisomers that are not mirror
images
o Have different physical properties
 Maximum number of stereoisomers : 2n, where n is
the number of chirality centres
SYMMETRY AND CHIRALITY
 A compound with one chirality centre will be chiral
 If more than one, could have rotational symmetry
and reflection symmetry
o Rotational: 180 about axis and still
superimposable
 o Reflectional: mirror across plane and are
still superimposable
 Rotational symmetry irrelevant to chirality
 If reflectional symmetry then achiral, if lack plane
of symmetry then generally achiral
o If no plane but has reflectional symmetry
through inversion about central point in
molecule, which is essentially reflection
about central point, then also achiral
 Meso compounds: even number >0 of chirality
centres, has plane of symmetry, achiral
o Meso compounds have less than predicted E and Z DESIGNATIONS FOR ALKENES
number of stereoisomers
FISCHER PROJECTIONS
 Horizontal lines represent attachments coming out
 Vertical lines represent going back into page
 Most useful for drawing molecules with multiple
chirality centres like sugars
o Quickly assess enantiomer, diastereomer,
meso relationships
CONFORMATIONALLY MOBILE COMPOUNDS
 Molecules can rotate around single bonds, but
chiral centres cannot invert configuration through ELECTRON DENSITY
single-bond rotations
 Conformations of butane are chiral but constantly
interconvert (enantiomers), so achiral compound
 (cis)-1,2-dimethylcyclohexane chiral but
interconvert and plane of symmetry (meso)
CHIRALITY WITHOUT CHIRALITY CENTRES
 Atropisomers: stereoisomers that would be
interchangeable through rotation of sigma bond,
but hindered rotation of single bond, but because,
different conformations are “stuck”
o Intermediate stage of conformational
change too high in energy, does not form
o Instead of chirality centres, have axis of
chirality; enantiomers
 Allenes: compounds that possess two adjacent C=C
double bonds; may or may not be chiral depending
on the substituents
o If two groups on each end of allene are
different, then will be chiral
o Have enantiomeric relationship
RESOLUTION OF ENANTIOMERS
 Most methods of separating compounds takes
advantage of different physical properties
o Distillation: based on boiling point
o Recrystallization: based on solubility
o But don’t work for enantiomers because
identical physical properties
 Pasteur performed first resolution of enantiomers
(formed mirror-image crystals) but doesn’t work
for most pairs of enantiomers
 Use chiral resolving agent: add enantiomer of
another compound, resulting reaction produces
diastereomeric salts
o Once separated, convert back into
enantiomers with base
 Affinity chromatography : equip glass column/tube
with chiral adsorbent; enantiomers will interact
different and travel through at different rates
 For molecules with different groups attached to
C=C double bond, E/Z notation used instead of
cis/trans notation
o Cis/tran only works if like group on each
carbon of the alkene
 1. Prioritize groups attached to C=C based on
atomic number (same as Cahn-Ingold)
 2. If top priority groups on same side, then Z, and if
on opposite sides, then E
 Many reactions of organic compounds occur
because atoms or bonds of high “electron density”
want to share electrons with atoms or bonds of
low “electron density”
 Wave is dense: electrons are more versus less
“present,” or high versus low probability of finding
them there
 Bromoethane
o Bromine has three lone pairs of electrons
(high density regions), more than its share
of electrons in C-Br bond because higher
EN, bears +, nucleophilic
o C1 has three non-polar bonds (neither
electron rich nor poor), less than its share
of electrons, bears -, electrophilic
o C2 and hydrogens: no lone pairs, all non-
polar bonds, neither nucleophilic nor
electrophilic
o Species that are electron rich react by
donating to C1 (e.g. OH-), species electron
poor react at Br (e.g. Ag+), C2 and H are
not charged and less reactive
 Ethene
o Pi orbitals contain most available (i.e.
highest energy) electrons: nucleophilic
o Adding electrons not favored because no
+ and only anti-bonding orbitals available
o Pi bond will react with electrophile