Stereochemistry

Constitutional Isomers: same molecular formula, different connectivity.

Stereoisomers: same molecular formula, same connectivity, different arrangement of atoms in space.

Consider the following molecules:

cis-1,2-dichlorocyclopentane trans-1,2-dichlorocyclopentane

What is their relationship?

H

H

Cl

Cl

Cl

H

Cl

H

These cis/trans isomers exist because…?

What about? C C

H3C

H CH2F

CH2Cl

C C

H3C

H CH2Cl

CH2F

which is cis and which is trans?

Substituents on each end are prioritized using the Cahn-Ingold-Prelog convention and the geometry is labelled as Z or E…

C C

Y

W X

Z

C C

higher priority

higher priority

C C

higher priority higher priority

Z isomer E isomer

Z – Zusammen (together) E – entgegen (across)

The Cahn-Ingold-Prelog Rules for Determining Substituent Priority:

Substituents are evaluated by comparing atoms that are equidistant from the point of interest.1. The higher the atomic number, Z, the higher the priority.2. For atoms with the same Z, the heavier isotope has higher priority (13C vs 12C, 2H(D) vs 1H).3. If the atoms attached are the same, then move out to the next ‘shell’ of atoms connected to each of the identical atoms and list them in decreasing atomic number. The group with an element having a higher Z at the first point of difference has the higher priority.4. If all the atoms in the second shell are identical, go to the next shell and repeat the process until the first point of difference is found.5. If a substituent contains π–bonds, interpret them as multiple σ–bonds between the same atoms (e.g. an aldehyde has a carbon which is bonded to 2 oxygen atoms and one hydrogen atom.

C

CH2F

CH2CH2Br

C

C

C

H OCH3

OCH3

HH

OCH3

C

CF3

CH2SH

Use the Cahn-Ingold rules to assign priority to the following groups…

What about multiple bonds (Rule #5 in the Cahn-Ingold Rules)?

C N

COH

O

C N

N00

N00

C000

C000

C

O

O0

O H

C000

C

C

C

CH3 CH3

CH3

C

H

Use the Cahn-Ingold Rules to assign priority to the following groups:

How do you know when molecules are the same?

Molecules are identical if, in equivalent conformations, they are superimposable.

C C

H3C

HH

CH2CH3

C C

H

HH3C

CH2CH3

C C

H

HH3C

CH2CH3

C C

H3C

HH

CH2CH3

If the connectivity of two molecules differs, then they are constitutional isomers. If the connectivity is the same but the molecules are not superimposable, then they are stereoisomers.

C

CH3Cl

H3CO

HC

CH3

Cl

CH3

OH

C

H

ClCH2CH3

CH3C

H

ClH3CH2C

H3C Are molecules A and B the same?

C

H

ClH3CH2C

H3C

A B

B

Configuration: the arrangement in space of the substituents around a given asymmetric atom.

Stereocenter (asymmetric, chiral, or stereogenic):

any tetrahedral atom,

frequently carbon, which has 4

different substituents.

Chirality and Enantiomers

Since these two molecules are nonsuperimposable mirror images of each other, they are called enantiomers and are said to be chiral.

Chirality (n): is a property of objects such that they are nonsuperimposable on their mirror image.

Chiral (adj): an object is chiral if it is nonsuperimposable on its mirror image.

Enantiomers: are stereoisomers that are nonsuperimposable mirror images of one another.

C

H

ClCH2CH3

CH3C

H

ClH3CH2C

H3C

Recall:

Achiral (adj): an object is achiral if it is superimposable on its mirror image. If an object has a plane of symmetry it is not chiral.

Enantiomers have identical physical properties in all respects (thus difficult to separate from each other), except they rotate plane-polarized light in opposite directions. Substances that rotate plane-polarized light are said to be optically active.

2-butanol: One molecule rotates plane polarized-light clockwise (+) while the other rotates plane-polarized light counter clockwise (-). Therefore, these two molecules would be named (+)-2-butanol and (-)-2butanol.

Thus a 50/50 mixture of two enantiomers (called a racemic mixture) will not rotate plane polarized light.

C

H

OHH3CH2C

H3C C

H

HOCH2CH3

CH3

Absolute configuration: the actual arrangement in space of the substituents around a given asymmetric atom that can be designated R or S. Also applies to E/Z.

Note how the ‘optical activity’ of molecules (+ vs -) says nothing about the absolute configuration around the chiral centre(s).

Thus a 50/50 mixture of two enantiomers (called a racemic mixture) will not rotate plane polarized light.

The Cahn-Ingold-Prelog Convention is used to assign the absolute configuration of a chiral centre.

•we assign priorities (1-4) to the substituents of a chiral atom.•orient the molecule such that the lowest priority substituent points away from you.•if the remaining substituents are arrayed 1-2-3 in clockwise order, then the center has R configuration.•if the remaining substituents are arrayed in a counter clockwise order, then the center has S configuration.

C

C

1

2 3

4

1 2

3

4

C12

3

4

12

3

4

=

=

R

S

Any molecule with a single asymmetric carbon atom must be chiral.

C

H

ClCH3

CH2CH3C

H

ClCH2CH3

CH3

There are only 2 possible configurations for chiral centres…

These two configurations cannot be interchanged without breaking bonds.

What happens when we switch two groups on an asymmetric carbon atom?

C

H

ClCH3

CH2CH3

Assign the configuration to all stereocentres:

C

CH2OH

HH3CCl

CH3

Cl

O

BrH

OO

Cl

H O

Cl

H

Can molecules without asymmetric atoms be chiral?

C C C

H

Cl

H

ClC C C

H

Cl

H

Cl

OH

HO

HO

OH

Atoms other than carbon...

NH3CH2C CH3

PhN

H3CH2C CH3

Ph

NH3CH2C Ph

CH3

CH3CH2Br

NH3CH2C CH3

Ph

CH2CH3

Br

PH3CH2C CH3

Ph

SH3CH2C

PhO

Molecules with two chiral centres…

H3C

C C

HO

BrH

HCH3

CH3

CC

OH

Br H

HH3C

H3C

C C

HO

HBr

HCH3

CH3

CC

OH

HBr

HH3C

Stereoisomers that are not enantiomers are called…

Diastereomers have different physical properties and can easily be separated from one another. A molecule can have a maximum of 2n possible stereoisomers (n = number of stereocenters).

Diastereomers: are stereoisomers that are nonsuperimposable, non-mirror images to each other.

1 2

3 4

H

Br

IH

ClBr

F CH3

For the following molecule, draw all stereoisomers and indicate which are enantiomers and which are diastereomers.

Recall 1,2-dichlorocyclopentane. How many stereocentres does 1,2-dichlorocyclopentane have? Draw all the stereoisomers for 1,2-dichlorocyclopentane.

Fischer Projections: a short hand notation for showing absolute configurations. In no way do these diagrams attempt to show the actual shape of molecules.

CH OH

CHO

CH2OH

CHO

CH2OH

H OH

90°

CHOHOH2C

H

OH

==

CHOHOH2C

H

OH

180°

CHO

CH2OH

HHO=C HHO

CHO

CH2OH

=

A 90° or 270° rotation of a Fischer projection generates…

A 180° rotation of a Fischer projection generates…

Use models to convince yourself this is true!

Fischer projections were developed to aid in drawing molecules (sugars, actually) with many chiral centres. It is easy to spot enantiomers and superimposable molecules when drawn as these projections.

CHO

HO H

HO H

CH2OH

CHO

OHH

OHH

CH2OH CHO

HO H

HO H

CH2OH

CHO

HO H

H OH

CH2OH

StereochemistreeStereochemistree

Is the connectivitythe same?

Yes No

Constitutional isomersAre theysuperimposable?

Identicalmolecules

They are stereoisomers.Are they mirror imagesof each other?

Enantiomers Diastereomers

No

Yes

Identical after rotation about single bondsto equivaent conf ormations?

Yes

No

Conformers

NoYes

Do they have the samemolecular f ormula?

Yes No

Different molecules