Difficulty: Intermediate to Advanced | Prerequisites: CIP priority, R/S assignment, enantiomers vs diastereomers, basic reaction mechanisms
This set of notes ties stereochemistry to two larger themes: how chirality affects biological function (enzymes are stereospecific, so enantiomers of sugars and drugs behave differently in the body), and how chemists use stereochemistry as a diagnostic tool to work out reaction mechanisms (the alkyne-to-alkene reduction). The exam tested these ideas through a Star Trek scenario involving mirror-image biochemistry and through a series of questions about choosing the right alkyne to reveal whether a reduction is syn or anti. If you are comfortable with enantiomers, diastereomers, and optical rotation, this material builds naturally on that foundation.
Enantiomers rotate plane-polarised light by equal amounts in opposite directions, so the mirror image of a sugar with optical rotation +72° has optical rotation -72°. Diastereomers have entirely different physical and chemical properties. Enzymes are chiral catalysts that bind one enantiomer but not its mirror image. The Na/NH₃ reduction of internal alkynes gives trans alkenes (anti addition), which tells us the mechanism delivers hydrogens to opposite faces, unlike catalytic hydrogenation (syn addition).
Optical rotation (specific rotation)
The degree to which a chiral compound rotates plane-polarised light. Measured with a polarimeter. A positive value (+) means the compound rotates light clockwise (dextrorotatory); a negative value (-) means anticlockwise (levorotatory). Think of it as the fingerprint of a chiral compound's handedness.
Enantiomer
The non-superimposable mirror image of a chiral molecule. Enantiomers have identical physical properties (melting point, boiling point, solubility) except for the direction of optical rotation, which is equal and opposite.
Diastereomer
A stereoisomer that is not a mirror image. Diastereomers have different physical and chemical properties (different melting points, different solubilities, different reactivity with enzymes).
Constitutional isomer
A molecule with the same formula but different connectivity. Constitutional isomers have completely different physical and chemical properties, just as diastereomers do, but for a different reason: the bonds are arranged differently.
Enzyme specificity (stereospecificity)
Enzymes are proteins with chiral active sites. They bind substrates based on 3D shape, so an enzyme that processes one enantiomer of a sugar will typically not process the mirror image. In simple terms, a left-handed glove does not fit a right hand.
Alkyne
A hydrocarbon with a carbon-carbon triple bond (C≡C). Alkynes can be reduced to alkenes or alkanes.
Internal alkyne
An alkyne where the triple bond is flanked by carbon groups on both sides (e.g. 2-butyne, CH₃C≡CCH₃), as opposed to a terminal alkyne (RC≡CH) where one end is a hydrogen.
Trans alkene
An alkene where the two larger substituents are on opposite sides of the double bond. The Z/E system is the formal version: E corresponds to trans in most cases.
Syn vs anti addition (in alkyne context)
Syn addition delivers both hydrogens to the same face of the triple bond, giving a cis alkene. Anti addition delivers them to opposite faces, giving a trans alkene.
Mirror-image molecules and optical rotation
If a chiral compound has a specific rotation of +72°, its enantiomer has a specific rotation of -72°. The magnitudes are always equal; only the sign changes.
A racemic mixture (50:50 enantiomers) shows zero net rotation.
The "Trekose" example from the exam
Trekose is a sugar found in "good" Spock's body with optical rotation +72°.
"Evil mirror" Spock's biochemistry is inverted, meaning every stereocentre in his version of the sugar is flipped. That makes his sugar the enantiomer of Trekose.
The enantiomer of Trekose has optical rotation -72°.
Drawing the enantiomer of a sugar
Take the Haworth projection or Fischer projection and invert every stereocentre (swap every wedge and dash, or swap left and right on a Fischer projection).
The connectivity stays the same. Only the 3D arrangement changes.
Diastereomers of a sugar: different physical and chemical properties
The exam also asked for a stereoisomer with "completely different physical and chemical properties." That is a diastereomer, not an enantiomer.
To draw a diastereomer, invert some but not all stereocentres. Alternatively, draw a constitutional isomer (different connectivity entirely), which also has entirely different properties.
A diastereomer qualifies because it differs in melting point, solubility, reactivity, and optical rotation (not just the sign).
Why enzymes distinguish enantiomers
Enzymes are proteins made of L-amino acids, so their active sites are chiral environments.
A substrate fits the active site the way a hand fits a glove: the shape, charge distribution, and hydrogen-bonding pattern must match in three dimensions.
The enantiomer of a natural substrate has the wrong 3D arrangement at every stereocentre, so it cannot bind properly. The enzyme either processes it very slowly or not at all.
The "good Spock vs evil mirror Spock" reasoning
Good Spock's enzymes evolved to process Trekose (the natural enantiomer).
Evil mirror Spock's enzymes are themselves mirror images of good Spock's enzymes (made from D-amino acids in the mirror universe). They would process the enantiomer of Trekose.
If you fed Trekose to evil mirror Spock, his mirror-image enzymes could not process it, because the substrate-enzyme fit is wrong in every chiral dimension.
Real-world parallel
This is the same reason the pharmaceutical industry cares about chirality. Ibuprofen, for instance, has one enantiomer that is an effective anti-inflammatory and another that is inactive. Regulatory agencies increasingly require drugs to be sold as single enantiomers rather than racemic mixtures.
The reaction
Na/NH₃ (dissolving metal reduction) reduces a C≡C triple bond to a C=C double bond.
The product is an alkene, and the key question is: is it cis or trans?
The answer: trans alkene (anti addition)
Na/NH₃ reduction of an internal alkyne gives the trans (E) alkene exclusively.
This means the two hydrogen atoms are delivered to opposite faces of the former triple bond.
Contrast with catalytic hydrogenation
Catalytic hydrogenation (H₂/Pd or H₂/Pt of alkenes) delivers both hydrogens from the metal surface to the same face: syn addition, giving the cis product.
The alkyne Na/NH₃ reduction gives the opposite stereochemistry (trans), which tells us the mechanism must be fundamentally different.
What this means for the mechanism
If catalytic hydrogenation delivers both H atoms simultaneously from one face (syn), and the Na/NH₃ reduction gives trans, then the Na/NH₃ mechanism cannot involve simultaneous delivery of both hydrogens from one face.
The hydrogens must arrive stepwise, from opposite sides, or through an intermediate that allows the geometry to settle into the trans arrangement.
This is a powerful example of using product stereochemistry to deduce mechanistic information.
The problem
To determine whether a reduction gives cis or trans, you need to be able to tell the difference in the product. That means the product alkene must have distinguishable cis and trans isomers.
Why acetylene (HC≡CH) does not work
Acetylene is a symmetric terminal alkyne. Reduction gives ethylene (H₂C=CH₂), which has no cis/trans isomerism because both ends of the double bond are identical (two hydrogens on each carbon). You cannot tell syn from anti addition.
Why propyne (HC≡C–CH₃) does not work
Propyne is a terminal alkyne (one end is H). Reduction gives propene (CH₃CH=CH₂). Propene has only one substituent on one side of the double bond and two hydrogens on the other, so there is no cis/trans isomerism. Again, you cannot distinguish the stereochemistry of addition.
What does work: an internal alkyne with two different groups
You need an alkyne of the form R₁–C≡C–R₂ where R₁ and R₂ are different non-hydrogen groups (e.g. 2-butyne is borderline, but any asymmetric internal alkyne is ideal).
The reduction product R₁CH=CHR₂ then has clear cis and trans isomers. If the product is exclusively trans, that is diagnostic for anti addition.
A suitable example
2-pentyne (CH₃C≡CCH₂CH₃). Reduction gives pent-2-ene, which has distinct cis (Z) and trans (E) forms. Observing exclusively the trans product confirms anti addition.
Students often think enantiomers have different physical properties. They do not. The only measurable difference is the sign of optical rotation (and interaction with other chiral agents, such as enzymes).
Students often confuse "different physical and chemical properties" (diastereomer or constitutional isomer) with "opposite optical rotation" (enantiomer). The exam specifically asked for a stereoisomer with completely different properties, which means a diastereomer, not an enantiomer.
Students often try to use a terminal alkyne to test stereoselectivity. Terminal alkynes reduce to terminal alkenes that lack cis/trans isomerism, so they cannot reveal the stereochemistry of the addition.
Students often assume that because catalytic hydrogenation of alkenes is syn, the Na/NH₃ reduction of alkynes must also be syn. The Na/NH₃ reduction is anti, giving trans alkenes.
⚠️ The optical rotation of an enantiomer is equal in magnitude and opposite in sign. If Trekose is +72°, its enantiomer is -72°. Full stop.
⚠️ When the exam asks "why can good Spock's enzymes process Trekose but evil mirror Spock's cannot," the answer centres on chirality: enzymes are chiral, substrates are chiral, and the fit is stereospecific.
⚠️ To test the stereoselectivity of an alkyne reduction, you need an internal alkyne with two different substituents. This is a multi-part reasoning question worth 22 points, so practise explaining it in writing.
Fill in the blank: The enantiomer of a compound with optical rotation +25° has optical rotation ___.
True or False: Diastereomers have the same boiling point.
Fill in the blank: Na/NH₃ reduction of an internal alkyne gives a ___ alkene.
True or False: Acetylene (HC≡CH) is a suitable substrate to test whether a reduction is syn or anti.
True or False: An enzyme made of L-amino acids can process the enantiomer of its natural substrate equally well.
Answers: 1. -25°. 2. False (diastereomers have different physical properties). 3. Trans. 4. False (the product ethylene has no cis/trans isomerism). 5. False (the chiral active site is specific to one enantiomer).
Q: A naturally occurring amino acid has specific rotation +13.5°. What is the specific rotation of its enantiomer?
A: -13.5°. Enantiomers always rotate light by the same magnitude in opposite directions.
Q: You are given a sugar with four stereocentres. You invert two of them. Is the resulting compound an enantiomer or a diastereomer of the original?
A: A diastereomer. Only when all stereocentres are inverted do you get the enantiomer. Inverting some but not all gives a diastereomer.
Q: Explain in one sentence why an enzyme that digests D-glucose cannot digest L-glucose.
A: The enzyme's chiral active site is complementary to the 3D shape of D-glucose, and L-glucose (the enantiomer) does not fit that active site, so the reaction cannot proceed.
Q: Why is propyne unsuitable for determining whether the Na/NH₃ reduction is syn or anti?
A: Propyne is a terminal alkyne, so its reduction product (propene) lacks cis/trans isomerism. There is no stereochemical difference to observe, regardless of whether the addition is syn or anti.
Q: The Na/NH₃ reduction of 2-butyne gives exclusively trans-2-butene. What does this tell us about the mechanism, given that catalytic hydrogenation of alkenes delivers both H atoms from the same face?
A: The trans product means the two hydrogens end up on opposite faces (anti addition). Since catalytic hydrogenation is syn (same-face delivery), the Na/NH₃ mechanism must operate differently, delivering hydrogens stepwise from opposite faces rather than simultaneously from one face.
Optical activity and enzyme specificity connect to biochemistry courses, where the chirality of amino acids, sugars, and drug molecules is a recurring theme. The alkyne reduction material previews CHEM 238 content and illustrates a broader principle: stereochemical outcomes are diagnostic of mechanism. This same logic applies to SN2 (inversion) vs SN1 (racemisation), which you may encounter later in the course or in CHEM 238.
optical rotation, specific rotation, polarimeter, dextrorotatory, levorotatory, enantiomer, diastereomer, chiral, achiral, enzyme specificity, stereospecific, lock and key, active site, D-sugar, L-sugar, Trekose, mirror image biochemistry, alkyne reduction, dissolving metal reduction, Na NH3, Birch reduction, trans alkene, anti addition, syn addition, cis alkene, internal alkyne, terminal alkyne, 2-butyne, catalytic hydrogenation, stereoselectivity, mechanism probe, CHEM 237, CHEM 238, organic chemistry, University of Washington