Lecture on Absolute Configuration

Introduction

• Absolute configuration describes the spatial position of atoms or groups in a chiral center.
• Chiral centers are atoms bound to four different substituents.
• Absolute configuration designates each chiral center as either 'R' or 'S'.
• Difference from relative configuration: Absolute does not depend on the position relative to other groups.

Assigning R or S Configuration

1. Assign Priorities Using Cahn-Ingold-Prelog (CIP) Rules
   • Rank substituents by atomic number (number of protons).
   • If atomic numbers are the same, use atomic mass.
   • If both atomic number and mass are the same, find the first point of difference.
   • Double and triple bonds are treated as multiple single bonds.

Example

• Chiral center with substituents: Hydrogen, Hydroxyl, Amine, Methyl
  • Oxygen (highest atomic number) is priority 1.
  • Nitrogen is 2, Carbon is 3, Hydrogen is 4.
• When isotopes (like hydrogen and deuterium) are involved, use atomic mass.
• For equivalent atomic numbers and masses, find the first point of difference in connected atoms.

Handling Multiple Bonds and Equivalent Atoms

• Treat multiple bonds as multiple single atoms.
• Example: A substituent double-bonded to oxygen counts as two oxygens.

Steps in Assigning Priorities

• Example 1:
  • Atom with substituents: Hydrogen, two different carbons, and a hydroxyl group.
  • Hydrogens are lowest, hydroxyl is highest.
  • For carbons, compare atoms they're bonded to.
• Example 2:
  • Central atom with Hydrogen, Nitrogen, two Carbons.
  • Identify first point of difference between similar carbons.

Final Configuration Determination

• Orient the lowest priority substituent in the back.
• Determine the order of the remaining substituents (1 to 3):
  • Clockwise: R
  • Counterclockwise: S
• Use the right-hand rule to avoid redrawing:
  • Thumb points to priority 4, fingers curl from 1 to 2 to 3.
  • If curl is 1 to 3 to 2, configuration is S.

Right-Hand Rule for Organic Chemistry

1. Thumb points to lowest priority (4).
2. Fingers point to highest priority (1).
3. Curl fingers to sequence through substituents:
   • 1 to 2 to 3: R
   • 1 to 3 to 2: S

Examples with Right-Hand Rule

• Example A:
  • Hydrogen in plane of page, priority 1 down and left.
  • Curl 1 to 2 to 3, configuration is R.
• Example B:
  • H going into page, priority 1 in plane.
  • Curl 1 to 3 to 2, configuration is S.
• Fischer Projection Tips:
  • Horizontal substituents come out of page (hug analogy).
  • Vertical substituents go into page.

Conclusion

• Follow CIP rules carefully to avoid errors.
• Right-hand rule helps visualize configuration without redrawing.
• Practice with different molecular orientations is essential.