Chapter 3: Stereochemistry

Learning Objectives

By the end of this section, you should be able to:

 Describe the classification of stereoisomers
 Illustrate staggered/ eclipsed conformations using Newman projections
 Illustrate chair/boat conformational isomers for cyclohexane rings and relate them to stability
 Identify axial/equatorial positions on cyclohexane rings
 Illustrate optical and geometric (cis-trans-) isomers
 Identify chiral molecule by locating its stereogenic centre
 Draw enantiomers of chiral molecule using perspective formula, wedge-and-dash and Fischer
projections
 Determine the absolute configuration of a 3-dimensional chiral molecule using R/S notation
system

Isomers
 Isomers: compounds that have the same molecular formula but are not identical
 Conformational isomers
 Conformational isomers or conformers are stereoisomers that can rapidly interconvert at room temperature. Because they interconvert rapidly,
conformational isomers cannot be separated (isolated). They have the same structural formula but differ in orientations of atoms in a 3D space.

1. Rotation about C-C single bonds (type of conformational isomer)

 Conformation isomers result from the fact that there is free rotation about a C–C single bond. So compounds that contain C–C single bonds have many
interconvertible isomers
 Energy required to rotate the conformers is called rotation energy
 The different isomers (conformations) can be represented by Newman projections
Newman projection (simple molecules):
 View the C-C bond along the axis of the bond
 Bonds from the centre of the circle are one the front, those along the perimeter are from rear carbon
Eclipsed conformation (atoms perfectly aligned) Staggered conformation  (atoms not aligned)

Higher energy conformation  higher steric repulsion Lower energy conformation lower steric repulsion
Rotating the rear carbon (learn to visualise)  red H is the target

 The staggered conformation is more stable compared to the eclipsed because in eclipsed conformation there is steric repulsion of the atoms/groups
 Newman projections for cycloalkanes (cyclohexane):
 Although the C-C bonds are not freely rotatable, it has 2 common conformations from partial rotation of C-C single bonds:
1. Chair MEMORISE E,A and Perspective formula 2. Boat (NO NEED TO KNOW HOW TO DRAW)

 More stable than ‘boat’ as it is strain free  less stable than ‘chair’ as there is steric
 Stable conformations are the ones where bulky substituents are located at di-equatorial positions repulsions of substituents at axial positions
than axial positions to avoid 1,3 diaxial repulsions  This is also known as steric repulsion of
 Lower energy conformation flagpole atoms/molecules.
 Higher energy conformation
 Conformers are interconvertible by a ring flip
 A ring flip results in the groups in the equatorial position  axial position vice versa. However groups will remain “up” or “down”

3. Planar conformation is not very common

Configurational isomers
Configurational isomers are stereoisomers that can cannot interconvert unless a covalent bond breaks. Because they cannot interconvert, and differ in at
least 1 chemical &/or physical property configurational isomers can be separated (isolated)

1. Geometric isomers (Cis and Trans isomers)

 The alkenes and cycloalkenes (C=C double bonds) can exhibit geometric isomerism because there is no free rotation at the C=C double bond, and there
is restricted rotation within a disubstituted ring.
 They differ in geometric orientation of atoms, not in the structural arrangement.
Cis-Trans isomers:
This only applies to disubstituted alkenes 
 Compounds that have 2 non-identical substituents (NOT GRPS!) on each of the doubly bonded carbon atom
 OR 2 non-identical substituents (NOT GRPS!) on each of the 2 adjacent carbon atoms in a cycloalkane ring.
Cis isomers Trans isomers

H/CH3 groups are on the same side of different ends of double bond H/CH3 groups are on the different sides of different ends of double bond

H groups are on the same end/plane (1 axial down & 1 equatorial down) H groups are on different ends/planes
(Can also be 1 equatorial up & 1 axial up)
 The 2 similar/ identical groups (can refer to H) are on the same side  The 2 similar or identical groups (can refer to H) are on opposite sides
 Tip: in practice u can also look if at the substituents’ side  Tip: in practice u can also look if at the substituents’ side
 Cannot be changed into one another (unless covalent bods are broken and reformed) ie. Are non-interconvertible

Alkenes with 2 identical groups at one end of the double bond do not have geometric isomerism (e.g. But-1-ene)

2. Optical isomers
 Contains a carbon bonded to four different substituents termed a stereogenic centre (or a stereo centre)  indicated by an asterisk (*)

 A compound with a stereogenic centre can exist as 2 different isomers, known as enantiomers.
 A molecule that has a non-superimposable (cannot be arranged to be the same) mirror image is a chiral molecule. Chiral molecules must have at least
one stereogenic centre and do not contain a plane of symmetry. Optically active molecules
 Achiral molecules contain a plane of symmetry. An achiral compound and its mirror image can be superimposed. Achiral molecules cannot exist as
enantiomers.

Ways to draw enantiomers once the stereogenic centre has been determined
Perspective formulas Wedge-and-dash Fischer projection formulas
 - Draw the 1st enantiomer by arranging by
arranging the 4 different groups bonded to the
stereogenic centre in any order.
- Draw the 2nd enantiomer by making a mirror
image of the 1st enantiomer  interchanging the 2
groups of the wedge and dashes
- Draw the 1st enantiomer by arranging by
arranging the 4 different groups bonded to the
stereogenic centre in any order.
- Draw the 2nd enantiomer by interchanging
any of the 2 groups.
- Same as Wedge and dash
- But use perpendicular lines to represent the bonds projecting
away and horizontal lines to represent bonds projecting towards

Naming Enantiomers using the R,S system

The R,S system of nomenclature indicates the configuration of an enantiomer. For any pair of enantiomers, one will have an R configuration and another with S configuration.
Perspective formulas Wedge-and-dash Fischer projection formulas

1. Rank first atoms attached to the stereogenic centre 1. Rank atoms attached to the stereogenic centre
according to atomic number (↑ atomic no. ↑ priority), if according to atomic number (↑ atomic no. ↑ priority), if
there is a tie, look at the next highest priority atom bonded to there is a tie look at the next atom that is joined to the
the C ruled out , note for double bonds take it as 2 atoms target one
bonded to centre C*
2. If the #4 priority is on a dash (behind):
2. Rotate the molecule to your perspective OR switch 2 - Clockwise = R
atoms such that #4 is at the back (dash line) and reverse the - Anticlockwise = S
rules where R to s or S to r If the #4 priority is on a wedge (front), reverse the
rules:
3. If the #4 priority is on a dash (behind): - Clockwise = S
1. Rank atoms attached to the stereogenic centre
according to atomic number (↑ atomic no. ↑ priority), if
there is a tie look at the next atom that is joined to the
target one
2. If the #4 priority is on a vertical line (behind):
- Clockwise = R
- Anticlockwise = S
If the #4 priority is on horizontal line (front), reverse
the rules:
- Clockwise = R
 - Clockwise = R - Anticlockwise = R - Anticlockwise = S
- Anticlockwise = S
If the #4 priority is on a wedge (front), reverse the rules:
- Clockwise = R
- Anticlockwise = S
It #4 is on a planar, exchange atom so #4 is behind and
reverse the rules.
 Note the ‘back carbon’ is always
downward ‘Y’ and front carbon is an
upward ‘Y’

For this case to visualize, rotate the

eye and molecule to your perspective
Draw the R and S configuration of the structure below