MEDCHEM.2 Chirality II – Assignment of R- and S-configurations

What rules are used to assign (R) and (S) enantiomers

Cahn-Ingold-Prelog rules are used

Explain the steps of Cahn-Ingold-Prelog rules

1. Locate the chiral carbon

2. Assign the highest to lowest priority to the four atoms bonded to the chiral carbon according to their atomic number The higher the atomic number, the higher the priority

3. If there are 2 or more identical atoms, then priorities of the substituents are established by the sets of atoms one further bond away.

4. For multiple bonds, the order of priority is Triple> Double>Single

5. Rotate molecule so that the lowest priority group is at the back

6. Draw an arrow from the highest to lowest priority group

7. If the direction of the arrow is clockwise =(R) enantiomer

8. If the direction of the arrow is anti clockwise = (S) enantiomers

What is the Double-Switch Trick

In order to assign the stereochemistry you must be able to manipulate the structure on paper so that the lowest priority group is in the back orientation

Interchanging any two groups inverts the stereochemistry. So switch the lowest priority group to the desired position.

Then switch the other two groups. The “double-switch” does not change the stereochemistry.

What is the Fischer Projections

Horizontal line is coming out of the plane (towards you)

Vertical line is going back behind the plane of the paper (away from you)

How can the Fisher Projections can be rotated

The Fisher Projections can be rotated by 180 degrees ONLY

How can the Fisher Projections can be manipulated

If one group of a Fischer projection is held steady, the other three groups can be rotated clockwise or anticlockwise

How do you assign R and S configuration to Fischer Projections

1.Assign priorities to the four substituents according to the Cahn-Ingold-Prelog rules.

2.Perform the two allowed manipulations of the Fischer projection to place the lowest priority group at the top (or bottom).

3.If the priority of the groups 1-2-3 are clockwise then assign the center as R, if 1-2-3 are counterclockwise then assign the center as S.