Stereochemistry Constitutional Isomers: same molecular formula, different connectivity. Stereoisomers: same molecular formula, same connectivity, different arrangement of atoms in space. Consider the following molecules: cis-1,2-dichlorocyclopentane trans-1,2-dichlorocyclopentane What is their relationship?

These cis/trans isomers exist because…? What about? which is cis and which is trans?

Substituents on each end are prioritized using the Cahn-Ingold-Prelog convention and the geometry is labelled as Z or E… E isomer Z isomer Z – Zusammen (together) E – entgegen (across)

The Cahn-Ingold-Prelog Rules for Determining Substituent Priority: Substituents are evaluated by comparing atoms that are equidistant from the point of interest. 1. The higher the atomic number, Z, the higher the priority. 2. For atoms with the same Z, the heavier isotope has higher priority (13C vs 12C, 2H(D) vs 1H). 3. If the atoms attached are the same, then move out to the next ‘shell’ of atoms connected to each of the identical atoms and list them in decreasing atomic number. The group with an element having a higher Z at the first point of difference has the higher priority. 4. If all the atoms in the second shell are identical, go to the next shell and repeat the process until the first point of difference is found. 5. If a substituent contains π–bonds, interpret them as multiple σ–bonds between the same atoms (e.g. an aldehyde has a carbon which is bonded to 2 oxygen atoms and one hydrogen atom.

Use the Cahn-Ingold rules to assign priority to the following groups…

What about multiple bonds (Rule #5 in the Cahn-Ingold Rules)?

Use the Cahn-Ingold Rules to assign priority to the following groups:

How do you know when molecules are the same? Molecules are identical if, in equivalent conformations, they are superimposable. If the connectivity of two molecules differs, then they are constitutional isomers. If the connectivity is the same but the molecules are not superimposable, then they are stereoisomers.

Are molecules A and B the same? Chirality and Enantiomers Stereocenter (asymmetric, chiral, or stereogenic): any tetrahedral atom, frequently carbon, which has 4 different substituents. Configuration: the arrangement in space of the substituents around a given asymmetric atom.

Chirality (n): is a property of objects such that they are nonsuperimposable on their mirror image. Chiral (adj): an object is chiral if it is nonsuperimposable on its mirror image. Achiral (adj): an object is achiral if it is superimposable on its mirror image. If an object has a plane of symmetry it is not chiral. Enantiomers: are stereoisomers that are nonsuperimposable mirror images of one another. Recall: Since these two molecules are nonsuperimposable mirror images of each other, they are called enantiomers and are said to be chiral.

Enantiomers have identical physical properties in all respects (thus difficult to separate from each other), except they rotate plane-polarized light in opposite directions. Substances that rotate plane-polarized light are said to be optically active. 2-butanol: One molecule rotates plane polarized-light clockwise (+) while the other rotates plane-polarized light counter clockwise (-). Therefore, these two molecules would be named (+)-2-butanol and (-)-2butanol. Thus a 50/50 mixture of two enantiomers (called a racemic mixture) will not rotate plane polarized light.

Thus a 50/50 mixture of two enantiomers (called a racemic mixture) will not rotate plane polarized light. Note how the ‘optical activity’ of molecules (+ vs -) says nothing about the absolute configuration around the chiral centre(s). Absolute configuration: the actual arrangement in space of the substituents around a given asymmetric atom that can be designated R or S. Also applies to E/Z.

The Cahn-Ingold-Prelog Convention is used to assign the absolute configuration of a chiral centre. we assign priorities (1-4) to the substituents of a chiral atom. orient the molecule such that the lowest priority substituent points away from you. if the remaining substituents are arrayed 1-2-3 in clockwise order, then the center has R configuration. if the remaining substituents are arrayed in a counter clockwise order, then the center has S configuration. = R = S

There are only 2 possible configurations for chiral centres… These two configurations cannot be interchanged without breaking bonds. Any molecule with a single asymmetric carbon atom must be chiral. What happens when we switch two groups on an asymmetric carbon atom?

Assign the configuration to all stereocentres:

Can molecules without asymmetric atoms be chiral?

Atoms other than carbon...

Molecules with two chiral centres… 1 2 3 4 Stereoisomers that are not enantiomers are called… Diastereomers: are stereoisomers that are nonsuperimposable, non-mirror images to each other. Diastereomers have different physical properties and can easily be separated from one another. A molecule can have a maximum of 2n possible stereoisomers (n = number of stereocenters).

For the following molecule, draw all stereoisomers and indicate which are enantiomers and which are diastereomers.

Recall 1,2-dichlorocyclopentane. How many stereocentres does 1,2-dichlorocyclopentane have? Draw all the stereoisomers for 1,2-dichlorocyclopentane.

Fischer Projections: a short hand notation for showing absolute configurations. In no way do these diagrams attempt to show the actual shape of molecules. A 90° or 270° rotation of a Fischer projection generates… A 180° rotation of a Fischer projection generates… Use models to convince yourself this is true!

Fischer projections were developed to aid in drawing molecules (sugars, actually) with many chiral centres. It is easy to spot enantiomers and superimposable molecules when drawn as these projections.

Stereochemistree