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5.2 How to Assign R and S Configuration

Sep 30, 2025

Overview

This lecture explains how to assign absolute configurations (R and S) to chiral centers using the Cahn-Ingold-Prelog system, and how to name chiral molecules accordingly.

Chiral Centers and Absolute Configuration

  • Chiral centers are carbons bonded to four different groups, existing as non-superimposable mirror images (enantiomers).
  • The absolute configuration describes the spatial arrangement of these groups as R (rectus, right) or S (sinister, left).

Cahn-Ingold-Prelog Priority Rules

  • Assign priorities (1–4) to groups attached to the chiral center based on descending atomic number.
  • If two groups have the same first atom, compare the next set of atoms attached.
  • For double bonds, treat them as if the atom is bonded multiple times to the same atom.

Assigning R and S Configurations

  • Orient the molecule so the lowest priority group (4) is pointing away (dashed bond).
  • Trace a path from group 1 → 2 → 3:
    • Right-handed (clockwise) = R
    • Left-handed (counterclockwise) = S
  • If group 4 is toward you (wedge), reverse the result.
  • If group 4 is in the plane, swap it with another group, assign configuration, and invert the answer.

Complicated Scenarios and Tricks

  • For complex molecules, repeatedly compare atoms outward from the chiral center until the first difference is found.
  • Swapping any two groups on the chiral center gives the opposite configuration.

Naming Chiral Molecules

  • Name the molecule normally, then add the absolute configuration in parentheses at the start.
  • For one chiral center: (R)- or (S)- before the name, e.g., (R)-2-chlorohexane.
  • For multiple chiral centers: include location and configuration, e.g., (2R,3S)-2-chloro-3-methylhexane.

Key Terms & Definitions

  • Chiral Center — a carbon atom attached to four different groups.
  • Absolute Configuration — R or S label describing the 3D arrangement of groups on a chiral center.
  • Cahn-Ingold-Prelog Rules — a system for assigning priorities to substituents.
  • Enantiomers — non-superimposable mirror image molecules.
  • Stereocenter — any atom at which the interchange of two groups produces a stereoisomer.

Action Items / Next Steps

  • Practice assigning R and S configurations using the rules.
  • Try naming molecules with one or more chiral centers including the proper configuration labels.