_” STEREOCHEMISTRY “_

              Stereochemistry, a subdiscipline of chemistry, involves the study of the relative spatial arrangement of atoms within molecules. An important branch of stereochemistry is the study of chiral molecules.

Stereochemistry is also known as 3D chemistry because the prefix "stereo-" means "three-dimensionality".

The study of stereochemical problems spans the entire range of organic, inorganic, biological, physical and supramolecular chemistries. Stereochemistry includes methods for determining and describing these relationships; the effect on the physical or biological properties these relationships impart upon the molecules in question, and the manner in which these relationships influence the reactivity of the molecules in question (dynamic stereochemistry).

History and Significance

Louis Pasteur could rightly be described as the first stereochemist, having observed in 1849 that salts of tartaric acid collected from wine production vessels could rotate plane polarized light, but that salts from other sources did not. This property, the only physical property in which the two types of tartrate salts differed, is due to optical isomerism. In 1874, Jacobus Henricus van 't Hoff and Joseph Le Bel explained optical activity in terms of the tetrahedral arrangement of the atoms bound to carbon.

Cahn-Ingold-Prelog priority rules are part of a system for describing a molecule's stereochemistry. They rank the atoms around a stereocenter in a standard way, allowing the relative position of these atoms in the molecule to be described unambiguously. A Fischer projection is a simplified way to depict the stereochemistry around a stereocenter

1. What are we talking about?

        The bottom line of this whole chapter is learning the difference between isomers. There are two types of isomers, constitutional and stereoisomers. Constitutional isomers are two compounds that have the same atoms present, but differ in their connectivity. ie:

        These compounds contain the same number of atoms, but the oxygen has been moved to form an ether instead of an alcohol. Therefore, these compounds are constitutional isomers.

Stereoisomers also have the same atoms present, however the connectivity is the same. This means the same number of hydrogens will be attached to each carbon and the same number of carbons will be attached to each carbon. Picture this:

Now, these structures both appear to be the same, but careful observation will reveal that the amine groups attached are in the cis conformation on the left and the trans conformation on the right. Therefore, the same atoms are present, but just in a different spatial arrangement.

Not to beat this idea into your head, but here is another example of a stereoisomer, but this time we will use a hydrocarbon chain.

Notice that the chain on the left is in the cis conformation at the double bond and the chain on the right is trans. This makes them stereoisomers.

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2. I understand that chiral compounds are mirror images of each other that are not superposable, but how do I tell they are superposable?

          The easiest way to tell if the mirror image is superimposable or not and superposable is to find the stereochemistry at the stereocenter. This entails you to find the stereocenter first and then label the groups attached to it in order of their priority. This means the atom with the highest atomic number will be labeled A and the next highest B. The next step is to rotate the molecule so the D group is facing away from you.

ie.

If the groups go from A to C clockwise, it is in the R configuration. If the groups are arranged counterclockwise, it is in the S configuration.

Practice a few

A B C

          A has two stereocenters. The top stereocenter is an R configuration and the bottom stereocenter is an S configuration. For B the stereocenter is an S. C does not have to be considered because there are two of the same groups attached, and is not chiral.

If the two compounds you are looking at are mirror images of each other, but the configuration at the stereocenter differs, they are not superposable. Therefore they are chiral compounds. If they are superposable, then they are achiral.

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3. How do I tell the difference between an Enantiomer and Diastereomer?

       The easiest way to tell apart an enantiomer and a diastereomer is to look at whether or not the compounds are mirror images of each other. The best way to learn this is through practice. Here are a few examples, see if you can determine whether or not the compounds are enantiomers, the same, or diastereomers.

Hint: first determine if the compounds are mirror images of each other, and then find the individual stereochemistry around each chiral carbon. Remember the hand rule or the clockwise/counterclockwise arrangement discussed in the previous section.

D

        If you are having problems determining the configuration at each stereocenter, I suggest building a model.

A is a pair of diastereomers, because the configuration is S, S in the first compound and R,S in the second compound.

B is a tricky one. They are both in the trans configuration and there is a plane of symmetry. Also, notice there is no carbon with four different groups. Therefore, they are not enantiomers and there is no stereochemistry.

C does not have a carbon with four different groups, so it does not have a stereocenter either.

D is a pair of enatiomers. Notice they are mirror images of each other.

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4. There is an R and there is an S, but I don’t know what to do with them. Help!

If you have read the past few sections you know what the S and R designations are. They tell what type of stereochemistry is found at the stereocenter. Finding the stereochemistry at the stereocenters can help determine whether two compounds are enantiomers or diastereomers. Also, R and S versions of the same compound will have different optical activity values.

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5. Quick Review of optical activity

Optical activity is the only physical property that differs from one enantiomer to the next. Optical activity is measured when plane polarized light is passed through a compound. When the light passes through the compound, it is bent either with positive rotation (dextrorotary) or with negative rotation (levorotary). There is no correlation between positive or negative rotation with the S or R configuration. S can be either dextrorotary or levorotary and the R enantiomer will be the opposite of the S. The value given to optical activity is specific rotation. The equation to figure out specific rotation can be found page 203 in your textbook.

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6. Okay, I’m getting this stereocenter thing, but somebody had to go and screw everything up and stick two stereocenters together.

When dealing with two or more stereocenters on the same compound, there are a lot of possibilities. The first possibility is that the compounds are enantiomers of each other, the second that they are diastereomers, and finally that they can be meso compounds. Diastereomers occur when the compounds have the same chemical formula, but are not mirror images of each other.

ie.

Now look at these same atoms arranged differently to form an enatiomer. These compounds are mirror images of each other. However, they do have different stereochemistries, which makes them enantiomers.

You should also look at these next compounds and discover what makes them different from the above.

       These compounds appear to be enatiomers, because they are mirror images of each other. They really are not. The middle two compounds are the meso compound, since they are the same. The outside two compounds are enatiomers of each other. Therefore, a meso compound is observed with stereoisomers where you would expect four different possible structures (two pairs of enantiomers), but there are only three stereoisomers.

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7. Fischer Projections doesn’t mean a weekend out on the lake. How do I interpret them?

Fischer projections are a quick way to show three dimensions without the hassle of having to draw 3-D. They are very effective for those of us who lack artistic skills. When you look at the diagram the horizontal lines represent atoms that are coming out at you. The vertical lines mean they are going away from you. Fischer projections can be rotated 180 degrees and still be the same compound. However, if you flip it vertically or horizontally, it becomes the enantiomer.

This Fischer projection has been flipped horizontally. These two are enatiomers of each other. The first projection has an S, R configuration. The second projection has an R, S configuration.

Now lets look at a vertically flipped diagram.

T

hese compounds are enatiomers of each other.

Finally, notice what happens when the diagrams are rotated 180 degrees in the plane of the paper.

The configuration at each stereocenter remains the same.

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8. Cyclic Compounds

If you are anything like me, it is very hard for you to determine the stereochemistry in cyclic compounds the best way is just practice. Hopefully, this area will help. Do your best to determine the stereochemistry.

Analysis: