STEREOCHEMISTRY

the study of chemistry in three

dimensions

Recall the tetrahedral geometry of a

carbon with 4 attached groups
(Jacobus Vant Hoff and Joseph
Achille LeBel; 1874)

Examples: Geometric
butanedioic acid

isomers

of

CHIRAL MOLECULES optically active; not

superimposable on its mirror image (from Gk.
cheir meaning hand); no plane of symmetry;
with asymmetric center
ACHIRAL MOLECULES have a plane of
symmetry

mirror
images
are
superimposable

Usually a carbon atom with 4 DIFFERENT groups

Groups around a chiral carbon:

H
Different isotopes of the same element
Different alkyl groups
Different functional groups

Max. number of stereoisomer = 2n

DEFINITIONS:
OPTICAL ACTIVITY the ability of some molecules to
rotate the plane of polarized light in either of two
directions
SPECIFIC ROTATION the observed rotation when light
at 589 nm (sodium D line; yellow light from a sodium
lamp) is used with a sample pathlength of 1 decimeter
(1 dm) and a sample concentration of 1 g/mL

Jean Baptiste Biot (1835) studied the interaction of

substances with plane-polarized light

Optically active substances have the ability to rotate the plane of

polarized light

[a]D = _______observed rotation (degrees)_____= a/lxC

pathlength, l (dm) x concentration, C (g/mL)

Types of optically active substances

Dextrorotatory rotates light in the
clockwise direction
(d) or (+) - stereoisomer

Levorotatory rotates light in the

counterclockwise direction
(l) or (-) - stereoisomer

Examples:
Compound

[a]D

Sucrose
Cholesterol
Benzene
Acetic acid
Penicillin V
Monosodium Glutamate
Morphine

+66.47
-31.5
0
0
+233
+25.2
-132

L--amino acids
L-DOPA

D-ribose

L-aspartame

EXAMPLES OF BIOACTIVE CHIRAL MOLECULES: Explain why

these molecules are chiral.

STEREOCHEMICAL REPRESENTATIONS

Consider: lactic acid

How can you draw the stereoisomers of

lactic acid?

WAYS OF DRAWING CONFIGURATIONAL ISOMERS

A. Using the flying wedge projection

C
HO
H3C

COOH

(+) lactic acid

[a] = +3.82

C
HOOC

OH
CH3

(-) lactic acid

[a] = -3.82

By convention:
ordinary lines represent bonds in the
plane of the paper or the writing surface
dashed wedges represent bonds going
into the plane of the paper and away from
the observer
heavy wedges represent bonds going
towards the direction of the observer

B. Using Fischer projections (E. Fischer, 1891)

Vertical lines represent bonds oriented away

from the observer
Horizontal lines represent bonds oriented
towards the observer

COOH
Substituents on
HORIZONTAL
H
linesticking
out
towards
the viewer

Orient MAIN with

the MOST OXIDIZED
group on TOP

OH
CH3

Substituents on the
MAIN chain- bends
away
from
the
viewer

 Mirror images that are non-superimposable

 identical physical properties EXCEPT for the

direction of rotation of plane-polarized light
(d) or (+): clockwise
(l) or (-): counterclockwise
RACEMIC MIXTURE/ RACEMATE
- A solution containing EQUAL amounts of
enatiomeric pair
- (dl) or ()
- Optically inactive
- E.g., (dl)-Ibuprofen (Advil)

(+)-carvone

(-)-carvone

D-limonene
Orange odor

L-limonene
Lemon odor

Sweet

Bitter

CHIRAL RECOGNITION OF ENANTIOMERS BY

CHIRAL ENZYMES

 Non-mirror images & non-superimposable

With DIFFERENT physical & chemical properties
STEREOSOMERS with more than one chiral
center

For molecules with more than one chiral center:

MAXIMUM no. of stereoisomers = 2n

n= no. of chiral centers

EXAMPLE: Draw the stereoisomers of

H3C

H
C

H
C

OH

CH3

COOH

 Molecules with chiral centers but are ACHIRAL

due to the presence of a SYMMETRY plane
Chiral centers have same set of substituents
EXAMPLE: Draw the stereoisomers of
H
H
HOOC
C
C
OH

OH

COOH

ABSOLUTE CONFIGURATION
- how the different substituents of a
chiral carbon are arranged in tri-dimensional
space

if the first three high priority groups

rotate in a clockwise direction

if the three high priority groups

rotate in the counterclockwise
direction.

Rule 1. Look at the two atoms directly attached to each

and rank them according to atomic number.

Rule 2. If a decision cant be reached by ranking the first

atoms in the substituent, look at the second, third, or
fourth atoms away from the double-bond carbons
until the first difference is found.

Rule 3. Multiple-bonded atoms are equivalent to

the same number of single-bonded atoms.

Step [1]. Assign priorities from 1 to 4 to each group

bonded to the stereogenic center.

Step [2]. Orient the molecule with the lowest priority

group (4) back (on a dash), and visualize the relative
positions of the remaining three groups (priorities 1,
2, and 3).

Step [3] Trace a circle from priority group 1 to 2 to 3.

If tracing the circle goes in the clockwise direction
to the right from the noon positionthe isomer is
named R.
If tracing the circle goes in the counterclockwise
directionto the left from the noon positionthe
isomer is named S.

 The letters R or S precede the IUPAC name of the

molecule.
For the enantiomers of 2-butanol:

Move the lowest priority atom to the top (or bottom)

WITHOUT altering the absolute configuration.

1. Fix one group & rotate the other three.

2. Look at the other three & determine rotation.
CH3
H

OH
COOH

RULES FOR MANIPULATING FISCHER PROJECTIONS

1. Fischer projections can be rotated on the page by
180 this means that all four groups must
exchange places to get another projection for the
same molecule.

2. Another allowed rotation: Hold one group steady

while rotating the other three groups either in the
clockwise or counterclockwise direction.

3. Turning a Fischer projection by 90 or 270 inverts

its meaning the projection for the enantiomer
will be drawn; this is the same as interchanging
only 2 out of 4 groups.

CH3
H

Cl

Cl

H
CH3

COOH

(R)
H

OH

COOH

ENANTIOMER
HO

(R)
HO

(S)

(S)

COOH

OH
COOH

COOH
DIASTEREOMER

(R)

OH
(S)

OH
COOH
MESOFORM

DIASTEREOMER

Active analgesic

Inactive

Anti-inflammatory

Liver toxin

Anti-nausea

Teratogen

For a disubstituted alkene:

For a disubstituted alkene:

For RING structures:

For RING structures:

For a trisubstituted alkene:

If the higher-priority groups on each carbon are on the same

side of the doublebond, the alkene is designated Z, for the
German zusammen, meaning together.
If the higher-priority groups are on opposite sides, the alkene
is designated E, for the German entgegen, meaning
opposite.

CONFORMATIONAL ANALYSIS
Recall: s bonds are centrosymmetric there is
essentially free rotation about C-C single bonds of
alkanes.
several arrangements of groups around C-C single
bonds.
These different arrangements that are
interconvertible by mere bond rotation even at low
temperatures are called conformations.

Stereochemical representations of conformers

Consider ethane and propane:
Use the C1-C2 bond as the reference bond.

1. Newman projection

*** Note that bond rotation is not entirely free

2. sawhorse projection

Energy diagram:

Dihedral angle

* Similar diagram for propane but DGstrain = 3.4 Kcal/mol

Conformations :

Energy diagram:

Magnitude of repulsive interactions of neighboring

groups around C-C bonds: summary
Interaction
H H eclipsing interaction

Strain E
1 kcal/mol

Strain components
Torsional strain

CH3 H eclipsing interaction 1.4 kcal/mol Torsional and steric strain

CH3 CH3 eclipsing
2.5 kcal/mol Steric strain
interaction
CH3 CH3 gauche interaction 0.9 kcal/mol Steric strain

**GENERALIZATION: In the analysis of bigger alkanes, the

conformation that minimizes these components of strain energy
corresponds to the state of lowest energy or the most stable
conformation. The conformation that maximizes these repulsive
interactions corresponds to the state of highest energy or the
least stable conformation.

Higher alkanes most stable conformation is a zig-zag shape;

minimizes eclipsing strain and gauche butane interactions

CONFORMATIONAL ANALYSIS OF
CYCLOALKANES
Components of ring strain (Adolf von Baeyer (1885)
1.angle strain due to expansion or compression of
bond angles
2.torsional strain due to eclipsing of neighboring
bonds.
3. steric strain due to repulsive interactions of atoms
approaching too close to each other

measure of ring strain: heats of combustion

Rotation is not entirely free; motion is hindered so

that the ring wont break.

Consequences:
Cyclopropane has to be
planar has angle
strain, torsional and
steric strain

cyclobutane
has
a
puckered structure in
order to relive eclipsing
or torsional strain

Cyclopentane has
also a puckered
structure with the
5th carbon out of
plane with respect
to
the
other
carbons

p.5-4

Cyclohexane has 2 conformations free of angle strain:

compare these two conformations. What are the
Newman and sawhorse projections of the two
conformations?
BOAT
CONFORMATION

CHAIR
CONFORMATION

What are the two kinds of C-H bonds in chair

cyclohexane?
AXIAL BONDS - bonds that project vertically upward
or downward
EQUATORIAL - bonds that project diagonally upward
or downward

MONOSUBSTITUTED CYCLOALKANES: Preferred

conformation is the substituent in equatorial
position

Position of
substitution

cis

trans

1,2-

a,e or e,a

e,e or a,a

1,3-

e,e or a,a

a,e or e,a

1,4

a,e or e,a

e,e or a,a

Cis DISUBSTITUTED CYCLOALKANES: a,e & e,a are

the same.

Trans DISUBSTITUTED CYCLOALKANES: e,e is the

preferred conformation.

Chrysanthemic acid-active
insecticidal constituents of
chrysanthemum flowers

Prostaglandin E1- potent

hormone controlling
extraordinary functions
in humans