Difficulty: Intermediate | Prerequisites: Lewis structures, VSEPR, hybridisation (Ch. 1–2), conformational analysis (Ch. 4–5).
Stereochemistry is where organic chemistry stops being flat. Most biological molecules are chiral, meaning they exist as non-superimposable mirror images, and enzymes, receptors, and drug targets routinely distinguish one mirror image from the other. This set of notes covers chapters 6 and 7 (second half): how to spot chirality centres, assign their absolute configuration using the Cahn–Ingold–Prelog (CIP) rules, and determine whether a molecule is chiral or achiral. If conformational analysis and Newman projections still feel shaky, revisit those before diving in here.
A chirality centre is a carbon bonded to four different groups. You assign it R or S using the CIP priority rules, which rank substituents by atomic number. A molecule with chirality centres can still be achiral if it has an internal plane of symmetry (a meso compound). Exam questions test your ability to find these centres, assign configurations, and recognise when symmetry cancels out chirality.
Chirality centre (stereogenic centre, stereocentre, chiral carbon)
A carbon atom bonded to four different substituents. This is the most common source of chirality in organic molecules. In simple terms, if a carbon has four distinct groups attached, it is a chirality centre.
Chiral
A molecule that is not superimposable on its mirror image. Think of it as a molecule that has a "handedness," the way your left hand is not identical to your right.
Achiral
A molecule that is superimposable on its mirror image. In simple terms, the molecule and its mirror image are the same compound.
R and S configuration
Labels for the absolute spatial arrangement of groups around a chirality centre. R (from Latin rectus) means the priority sequence runs clockwise; S (from Latin sinister) means it runs anticlockwise. These are assigned using the CIP rules.
Cahn–Ingold–Prelog (CIP) priority rules
A systematic method for ranking substituents on a chirality centre by atomic number. Higher atomic number gets higher priority. When two atoms are identical, you move outward along the chain until a difference is found.
Plane of symmetry (mirror plane, sigma plane)
An imaginary plane that divides a molecule into two halves that are mirror images of each other. If a molecule has a plane of symmetry, it is achiral, even if it contains chirality centres.
Meso compound
A molecule that has chirality centres but is achiral overall because it possesses an internal plane of symmetry. Think of it as a molecule where one half cancels out the chirality of the other half.
Look for sp3-hybridised carbons bonded to four different groups. Ring carbons count, so trace the path in each direction around the ring to see whether the two "ring substituents" differ.
Implicit hydrogens are easy to overlook. If a carbon in a line drawing has three bonds drawn, the fourth substituent is hydrogen.
Heteroatoms (N, O, S) are not chirality centres in the usual introductory course context unless specifically discussed (nitrogen inverts rapidly in most amines, so it is not a stable stereocentre).
Identify the four substituents on the chirality centre.
Rank them by atomic number of the atom directly attached to the stereocentre: higher atomic number = higher priority. For example, Br (35) > O (8) > C (6) > H (1).
If two substituents start with the same atom, move outward along each chain until you reach a point of difference. Compare at that point.
Double and triple bonds are handled by the "phantom atom" rule: a C=O is treated as if the carbon is bonded to two oxygens (one real, one phantom) and the oxygen is bonded to two carbons (one real, one phantom).
Orient the molecule so the lowest-priority group (usually H) points away from you, straight back.
Read the remaining three groups in order of decreasing priority. If the sequence traces a clockwise arc, the centre is R. If anticlockwise, it is S.
Shortcut when H is coming toward you: If you cannot easily rotate the molecule so that H points away, assign the configuration as though H were already in the back, and then reverse the answer. Clockwise with H toward you = S. Anticlockwise with H toward you = R.
A molecule is chiral if it is not superimposable on its mirror image. The most reliable test is to look for a plane of symmetry. If none exists, the molecule is chiral.
A molecule with one chirality centre is always chiral.
A molecule with two or more chirality centres may or may not be chiral. If there is an internal plane of symmetry that maps one stereocentre onto another, the molecule is a meso compound and therefore achiral.
A cyclohexane with a substituent on C1 going up (wedge) and the same substituent on C4 going up (wedge) has a plane of symmetry through the ring. Even though C1 and C4 are both stereocentres, the molecule is achiral.
The key test: can you draw a plane that cuts the molecule into two halves that are mirror images of each other? If yes, the molecule is meso and achiral.
Pharmaceutical companies must control stereochemistry because one enantiomer of a drug can be therapeutic while the other is inactive or harmful. Thalidomide is the classic (and tragic) example: the (R)-enantiomer was a sedative, while the (S)-enantiomer caused birth defects. Modern drug design routinely targets single enantiomers.
Students often think that having chirality centres automatically makes a molecule chiral. It does not. A meso compound has chirality centres but is achiral because of an internal plane of symmetry.
Students sometimes confuse the direction of optical rotation (+/–) with R/S configuration. These are unrelated. R does not mean (+) and S does not mean (–). Optical rotation is an experimental measurement; R/S is an assignment based on CIP rules.
When the lowest-priority group is not pointing away from you, students frequently forget to invert the initial assignment. If H faces toward you and the priority sequence is clockwise, the correct answer is S, not R.
Students often try to assign R/S from a flat (2D) drawing without first thinking about the 3D arrangement. Wedge-and-dash notation exists for a reason: use it to establish which groups point toward you and which point away.
⚠️ Expect at least one question that gives a complex molecule (possibly with a ring) and asks you to find and label every stereocentre as R or S.
⚠️ Meso compounds appear frequently. You will likely be asked whether a molecule is chiral or achiral, and you need to check for a plane of symmetry before answering.
⚠️ Several past exam questions have tested whether two molecules are identical, enantiomers, diastereomers, or constitutional isomers. Knowing R/S is the fastest way to determine the relationship.
⚠️ CIP priority with double bonds (phantom atom rule) is a common exam stumbling point.
True or false: A molecule with exactly two chirality centres is always chiral.
False. It could be a meso compound.
Fill in the blank: When the lowest-priority group points toward the viewer and the remaining groups trace a clockwise arc, the centre is assigned ______.
S (you must invert because H is toward you).
True or false: R configuration always corresponds to (+) optical rotation.
False. There is no direct relationship between R/S and (+)/(–).
Fill in the blank: In the CIP system, a C=O double bond is treated as if the carbon is bonded to ______ oxygens.
Two (one real, one phantom).
True or false: An achiral molecule can contain chirality centres.
True. Meso compounds are the example.
Q: A molecule has two stereocentres, both with the same four substituents. One is R and the other is S. Is the molecule chiral or achiral? Explain.
A: Achiral. When two identically substituted stereocentres have opposite configurations (one R, one S), the molecule has an internal plane of symmetry. It is a meso compound.
Q: You are looking at a chirality centre where the lowest-priority group (H) is on a wedge (pointing toward you). The remaining three groups, in order of decreasing priority, trace an anticlockwise arc. What is the configuration?
A: R. Because H is toward you rather than away, you invert the initial reading. Anticlockwise with H toward you becomes R.
Q: Rank the following substituents by CIP priority: –CH₃, –OH, –NH₂, –Br.
A: Br (35) > OH (8) > NH₂ (7) > CH₃ (6). You rank by atomic number of the atom directly attached to the stereocentre.
Q: A cyclohexane ring has –Cl at C1 (wedge) and –Cl at C2 (dash). Is the molecule chiral? Why or why not?
A: Yes, it is chiral. The two chlorines point in opposite directions relative to the ring, so there is no plane of symmetry that maps one onto the other. Both C1 and C2 are stereocentres, and without a mirror plane the molecule is chiral (this is a pair of diastereomers relative to the cis isomer).
Q: Explain the phantom atom rule for a carbon involved in a C=C double bond when assigning CIP priorities.
A: A double bond between C and C is treated as if each carbon is bonded to a phantom copy of the other. So the carbon of the stereocentre "sees" two carbons (one real, one phantom) from the double bond, and the doubly bonded partner also "sees" an extra phantom. Phantom atoms have no further substituents.
Chirality connects directly to reaction stereochemistry (the next set of notes). Whether a reaction produces a single enantiomer, a racemic mixture, or a meso compound depends on the mechanism, and you need R/S fluency to describe the outcome. This topic also ties into biological chemistry: enzymes are chiral catalysts that interact with substrates in a stereospecific way, which is why (+)-glucose and (–)-glucose behave completely differently in your body.
Stereochemistry, chirality, chiral centre, stereogenic centre, stereocentre, asymmetric carbon, R configuration, S configuration, Cahn–Ingold–Prelog rules, CIP priority, absolute configuration, chiral vs achiral, plane of symmetry, mirror plane, meso compound, optical activity, enantiomers, handedness, non-superimposable mirror images, CHEM 237, organic chemistry, UW, University of Washington, chapters 6 and 7