Todd:Chem3x11 ToddL1

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Chem3x11 Lecture 1

This lecture is an overview of isomerism, then some material on stereocentres and what chiral molecules look like in ¹H NMR spectroscopy.

Key concepts

• There are two different kinds of stereoisomers
• Conformations of alkanes governed by sterics and electronics
• Prochiral centres become interesting in a chiral environment

Kinds of Isomerism

Constitutional isomers are the easiest to think about. The molecules are put together differently. Interview each atom in Molecule A in turn by asking "What other atoms are you bonded to?", then do the same for each atom in Molecule B. If the answers you get are different, Molecules A and B are constitutional isomers.

Scheme 1: Different connectivity: A simple example of constitutional isomers

Atoms in stereoisomers would give you the same answer since the atoms are connected to each other the same way, only the positions of the atoms in space changes. The easiest kind of stereoisomers to conceptualize are those around a double bond, i.e. E- and Z- isomers. To interconvert these you'd need to break the double bond, and when a bond needs to be broken we call that configurational isomerism.

Scheme 2: Same connectivity: A simple example of configurational isomers

Stereocentres are like that too, so enantiomers are configurational isomers.

Scheme 3: Same connectivity: Another simple example of configurational isomers

Stereoisomers you can interconvert without breaking any bonds are both interesting and not. The example below concerns alkanes, which seems silly because we never isolate the alkane isomers under normal conditions - the bond rotation is too easy/fast. But there are some very interesting and important examples of this kind of isomerism, particularly in Nature. Isomers of this kind, where all the atoms are connected to each other the same way, but there is a difference in the 3D arrangement of atoms BUT the isomers can be interconverted without breaking any bonds are called conformational isomers.

Scheme 4: Isomer Summary. Yes, all the terms begin with C

An Example of Conformational Isomers - The Rotations of Alkanes

Alkanes (acyclic ones) can rotate about each C-C bond. The different arrangements in space can be interconverted without breaking any bonds, and we call these structures conformational isomers. Typically the interconversion is super-fast and we can't isolate the separate isomers. If it becomes possible to see the separate isomers by e.g. ¹H NMR spectroscopy we sometimes call them rotamers, or, more formally and generally atropisomers.

Different conformational isomers have different arrangements of atoms in space, and these will have different energies, e.g. ethane, below.

Scheme 5: Conformational isomers of ethane

Why do these isomers interconvert so quickly? Pretty low barrier to rotation:

Scheme 6: Karplus Diagram for Ethane

For butane there is a greater preference for the conformation where the methyl groups are far apart. Everything's still moving very quickly, but the extended conformation (where the methyl groups are as far from each other as possible) is the lowest in energy. That's why we draw alkane chains as zig-zags, typically.

Scheme 7: Karplus Diagram for Butane

When butane is in one of its eclipsed conformations, the steric clashes explain the high energies.

Scheme 8: Eclipsed Conformations of Butane

In the staggered conformations, we should just learn a couple of commonly-used terms: gauche and antiperiplanar

Scheme 9: Meaning of the terms gauche and antiperiplanar, taken from the excellent Stereoelectronic Effects Oxford Chemistry Primer

The gauche conformation of butane still has a bit of a steric clash, and obviously the clashes are going to be lowest in the antiperiplanar conformation, which becomes our mental picture of butane, as the statistically most likely conformation.

Scheme 10: Gauche Conformation of Butane is Not the Lowest in Energy

Butane (and lots of other alkanes) are therefore easily understood in terms of sterics. But that's not the complete story. As with everything in organic chemistry, there is always a mixture of sterics and electronics. In ethane, for example, there are no "bulky" groups providing any steric clashes. There is still a small preference for the staggered conformation. But actually the energetic cost of the eclipsed conformation is surprisingly large, given that there are only H's "clashing" here.

Scheme 11: Surprisingly High Energetic Cost of Ethane's Eclipsed Conformation

To understand this, we should look at the orbitals involved. We humans draw a bond as a thin line. Remember it's a cloud of electrons, so a cloud of negative charge. So bonds don't like to be near each other. This is just another way of talking about a steric clash. But the fact that the H's in ethane are small shouldn't make us forget that the C-H bonds prefer not to be near each other either. So the eclipsed conformation is disfavoured because of a clash of the bonding electrons in the eclipsed bonds. We call this torsional strain.

Scheme 12: Electrons in Filled C-H σ Bonds Repel

There's something else, which is more subtle and which becomes important in lots of other cases we don't have time for. There is actually a benefit to the staggered conformation. The electrons in one C-H σ bond can overlap with the empty C-H σ* bond on the adjacent position. This would seem like a problem, but it's not. Any two-electron interaction between a filled orbital and an empty orbital is energetically favourable (i.e. bonding).

Scheme 13: Bonding-antibonding Interactions in Ethane's Staggered Conformation

A molecule is a complex electronic structure, and unexpected interactions between orbitals in three dimensions can explain a whole range of things that may seem puzzling when molecules are drawn as dull 2D objects.