Recap
In the previous part of this article, we discussed special cases of molecules which lack stereocenters (chiral centers) but still possess chirality, which is another reason why true determination of chirality can only result from the observation of whether plane-polarized light is rotated by that pure compound. The special phenomenon where, because of geometrical considerations or steric interactions, each side of a typically symmetrical molecule lacking stereocenters is forced to assume different orientations with respect to the plane of symmetry. This makes the molecule non-superimposable, and thus it possesses an enantiomer. Such a phenomenon is known as axial chirality, which we have already demonstrated for molecules such as biphenyls, hexahelicenes and cyclophanes. One important idea that we may have forgotten to mention in the previous article is the idea that for axial chirality to exist in a molecule, the molecule must not be planar - in any case where the molecule assumes planarity, it will always be superimposable on its mirror image if a plane of symmetry exists.
In the second part of the previous article, a new way of depicting molecules with optical activity was demonstrated. There is always inevitable complexity where the depiction of large molecules with many stereocenters, especially sugars, is attempted. The Fischer projection negates the tedious task of drawing out the dash and wedge bonds by assigning horizontal bonds to be wedge bonds and vertical bonds to be dash bonds. Lastly, the article also demonstrated a better way of naming different enantiomers, using the Cahn-Ingold-Prelog (CIP) system. This system prioritizes substituents with higher atomic numbers over substituents with lower atomic numbers, and using such a ranking system, the order in which the substituents are arranged is determined. Clockwise orientations lead to the assignment of the letter R, while anticlockwise orientations lead to the assignment of the letter S (Fig. 1). The prefix R or S is placed at the front of a molecule’s name to designate the enantiomer.
Fig. 1: Assignment of R or S prefixes.
Diastereomers
In the previous articles, the molecules we have discussed always only possess one single chiral center or stereocenter, and we have not yet considered the possibility of multiple chiral centers. Such a possibility is found in the compound 2,3,4,-trihydroxybutanal (Fig. 2). We observe that such a molecule has two stereocenters and the hydroxyl substituents on these stereocenters can be either facing away from the viewer or facing towards the viewer, creating a pair of enantiomers (mirror images), which we have already discussed previously. However, we note also that a separate pair of enantiomers is also possible, which have one hydroxyl substituent facing towards the viewer and the other facing away (this order is reversed in its enantiomer). It seems all fine. However, what when we consider the relationship between the earlier pair of enantiomers and this pair of enantiomers?
Fig. 2: Isomers of 2,3,4-trihydroxybutanal.
When we compare the two molecules in Fig. 2, we note that they are structural isomers and stereoisomers of each other. However, they cannot be considered enantiomers, because they are not mirror images of each other. In this case, the relationship between the two molecules is considered diastereomeric. We would like to take this opportunity to raise two very important points that we likely have neglected to mention before; firstly, the number of stereoisomers in a compound is given 2n, where n refers to the number of stereocenters in the molecule. So in the case of 2,3,4-trihydroxybutanal, it will have 4 (22) stereoisomers, since two stereocenters are present on the molecule. Many molecules generally stick to this rule, but there are two notable exceptions that we have discussed before, which are meso compounds (Fig. 3) and compounds which display axial chirality. In the first case, the stereocenter is present, but there will be one less stereoisomer because the meso compound displays no optical activity. In the second case, the stereocenter is absent, but the stereoisomer still exists because of axial chirality (although hypothetically speaking, 20 = 1).
Fig. 3: Example of a meso compound.
The second important thing to note is the definition of enantiomers and diastereomers. These are not ‘physical determiners’; we cannot assume that a compound is always a stereoisomer or always a diastereomer. This is because diastereomers and stereoisomers only describe the relationship between two stereoisomers. For example, while one compound may be the enantiomer of another, it can also be a diastereomer relative to yet another compound. The enantiomers and diastereomers are thus better termed ‘enantiomeric’ and ‘diastereomeric’ relationships. Now, let us look at the differences between enantiomers and diastereomers. The enantiomers, as we have noted before, have identical physical and chemical properties, but this is not so for diastereomers. Diastereomeric relationships entail highly similar properties, however, since the two compounds are still structural isomers.
Second and more importantly, a pair of enantiomers will always both be chiral, but this may not be true for a pair of diastereomers. This is mainly explained by the existence of the meso form. Since a meso compound has a plane of symmetry, it will not have an enantiomer, and this means that a pair of enantiomers will never contain a meso compound, confirming their chirality. In contrast, the diastereomer of a meso compound does not necessarily need to be achiral, because the diastereomer would cause only one of two stereocenters to invert. In a meso compound, the two stereocenters would be on each side of the plane, and when only one of them is inverted, the plane of symmetry would no longer exist, allowing for the diastereomer of a meso compound to be chiral.
More Isomerism
There are, of course, alternative types of isomerism, other than stereoisomerism. Firstly, there is the case of syn-anti isomerism (Fig. 4), which is related to stereoisomerism. Syn and anti isomers entail two molecules, with the same structural formula, that have two adjacent stereocenters. A further requirement is that on each of the stereocenters there must be at least one substituent (typically excluding the carbon backbone) which is not a hydrogen atom. Where the substituents being considered (relative to each other) point in the same direction, the molecule is syn (in Fig. 4, both substituents in wedge bonds). Where the substituents do not point in the same direction, the molecule is anti (one substituent in a wedge bond while the other is in a dash bond).
Fig. 4: Diagram of syn-anti isomerism.
Lastly for this article, we will discuss cis-trans isomerism (Fig. 5). In cis-trans isomerism we will be discussing two general cases: for noncyclics, and for monocyclics. In both cases, the isomerism arises from restricted rotation, where substituents which are oriented in a certain way are unable to rotate; this will be elaborated on later. In general, moieties which possess cis-trans isomerism include C=C bonds (alkenes) and C-C bonds in cyclic compounds (note that in both cases, rotation about the carbon-carbon bond is not possible). Assigning cis-trans is relatively easy; where the two substituents on the adjacent carbon atoms are syn to each other, the molecule is the cis isomer. When the two substituents are instead anti to each other, the molecule is the trans isomer. This applies to both the alkene and the cyclic compound case. Such a definition is applied to the simplest form of cis-trans isomerism, where assigning the cis- or trans- prefix in front of the name of a molecule is sufficient (as in cis-but-2-ene).
Fig. 5: Diagram of cis-trans isomerism.
In this last paragraph, we will be discussing the nomenclature in the case where all four substituents on the molecule are different. In this case, we cannot simply apply the cis-trans nomenclature because there are no two similar substituents on each carbon that can be compared. Instead, we use the E-Z nomenclature. Firstly, the four substituents are arranged by priority using the CIP system. In the isomer where the top two substituents (with the highest atomic numbers) are syn to each other, it is known as the Z isomer. When the top two substituents are anti to each other, it is known as the E isomer.
Part 2 of this article is here.