Stereochemistry: Chirality, Enantiomers, and Configurational Assignment

Core Review

Types of Isomers

• Constitutional isomers: Same molecular formula, different atom connectivity (e.g., butane vs. 2-methylpropane).
• Stereoisomers: Same connectivity, different spatial arrangement.
  • Enantiomers: Non-superimposable mirror images. MUST have opposite configuration at EVERY chiral center.
  • Diastereomers: Stereoisomers that are NOT mirror images. Differ at some (but not all) chiral centers.
  • Meso compounds: Have chiral centers BUT an internal plane of symmetry makes the molecule achiral (optically inactive).

Chirality and Stereocenters

A carbon is a stereocenter (chiral center) when it has four different groups attached. A molecule with one chiral center is always chiral. Molecules with multiple chiral centers may be chiral or meso (if an internal plane of symmetry exists).

Maximum number of stereoisomers = 2ⁿ where n = number of chiral centers. Meso compounds reduce this count from the theoretical maximum.

CIP Rules for R/S Assignment

1. Rank the four groups by atomic number of the atom directly attached to the chiral center. Higher atomic number = higher priority.
2. If there's a tie, move to the next atoms outward until a difference is found.
3. Multiple bonds are treated as the equivalent number of single bonds to that atom. (C=O is treated as C bonded to two oxygens.)
4. Orient the lowest-priority group (4) pointing away (dashed wedge).
5. Trace 1→2→3. Clockwise = R (rectus, right). Counterclockwise = S (sinister, left).
6. If group 4 is on a wedge (toward you), either mentally rotate OR assign as usual then flip (R→S or S→R).

For Fischer projections: If the lowest-priority group is on a vertical bond, trace 1→2→3 normally. If the lowest-priority group is on a horizontal bond, trace 1→2→3 then flip the answer.

E/Z Assignment for Alkenes

For each carbon of the double bond, assign priority to the two attached groups using CIP rules.

• (Z): Higher-priority groups on the same side (zusammen).
• (E): Higher-priority groups on opposite sides (entgegen).

Optical Activity and Specific Rotation

Enantiomers rotate plane-polarized light equally but in opposite directions. A (+) or (d) enantiomer rotates light clockwise; a (−) or (l) enantiomer rotates counterclockwise.

CRITICAL: R/S says NOTHING about (+)/(−). An R compound can be (+) or (−); these are unrelated properties determined only by experiment.

Racemic mixture: 50:50 mix of enantiomers → net rotation of 0 (optically inactive). Often denoted (±).

Specific rotation: [α] = α / (c × l), where α = observed rotation, c = concentration (g/mL), l = path length (dm).

Enantiomeric excess (ee): ee% = |[α]observed / [α]pure| × 100% = (% major − % minor).

Meso Compounds

A meso compound has 2 or more chiral centers but an internal plane of symmetry. It is achiral and optically inactive. Tartaric acid is the classic example: two chiral centers, but one stereoisomer (meso-tartaric acid) has a plane of symmetry.

Common Traps

• Assuming R = (+): The DAT loves testing this. R/S is a naming convention; optical rotation is an experimental measurement.
• Forgetting to check for meso: When a problem gives 2ⁿ stereoisomers but asks how many are optically active, subtract the meso compound(s).
• Fischer projection lowest-priority group: If group 4 is horizontal, trace 1→2→3 then INVERT. Students frequently forget this.
• Multiple bonds in CIP: C=O counts as C bonded to two oxygens (O,O). Not one "double-bonded O."
• E/Z vs. cis/trans: E/Z works for any alkene; cis/trans only works for disubstituted alkenes where each carbon has one H.