Stereoisomers

Naming of Enantiomers

Compounds with a chiral center, such as 2-butanol, can exist as two mirror image stereoisomers known as enantiomers. There are a number of ways to represent the enantiomers; in the columns below one of the enantiomers is shown on the left of the mirror plane and the other on the right.

The absolute configuration of an asymmetric atom is designated by the Cahn-Inglod-Prelog system (also known as the R,S system) that was introduced earlier in this program for (E) and (Z) alkenes. In this method the four different groups about a central atom are assigned priorities in a decending order (1, 2, 3 and 4) according to the sequence rules. Chiral centers are assigned (R) or (S) configurations depending of the spacial orientation of the priority sequence about the center. There are a number of ways to visualize and assign (R) or (S) configurations from the various types of stereochemical structures. Various textbooks recommend different methods. The primary method used here will rely on Fischer projections. To use the method one should practice converting other stereochemical representations to Fischer projections. Molecular models are very helpful in learning these techniques.

First we will review the sequence rules.

Sequence Rule 1

Groups are arranged in priority in order of decreasing atomic number of the groups attached to a carbon.

Atoms commonly encountered in organic compounds from high to low priority:

I Br Cl S P Si F O N C B H

Sequence Rule 2

If atoms attached directly to a carbon are the same, the one substituted with atoms of higher atomic number takes precedence.

In the above examples, look at the two groups attached to the green carbons. In both instances the atom directly attached is a carbon, so no decision of priority can be made. In the left hand case the first carbon is further attached to two hydrogens (At. No. 1) and a carbon (At. No. 12). In the right hand case, the first carbon is further attached to two hydrogens (At. No. 1) and a bromine (At. No. 35). The right example, therefore, is of higher priority.

If the second array of atoms permits no choice, the third atoms out are examined, etc. etc.

Sequence Rule 3

If an atom is attached to another atom by multiple bonds of the p-p p (double or triple in the case of carbon) both atoms are regarded as being replicated.

Sequence Rule 4

An isotope of higher mass number takes precedence, i.e., D has higher priority than H.

As a first example we will return to the Fischer projections of the enantiomers of 2-butanol.

Using the sequence rules assign priority numbers 1 to 4 to the groups about the chiral center and write these numbers on a duplicated Fischer projection. In the cases above the OH is 1, CH₃CH₂ is 2, CH₃ is 3 and H is 4.

With the lowest priority number (4) at the bottom, the remaining priority numbers are then read in order (1 -> 2 -> 3). If the sequence goes clockwise the chiral center is designated (R). A counterclockwise order is given the designation (S).

^{1. Assign the (R) or (S) absolute configuration to the following compound.

One trick to assigning (R) or (S) by a consistent process is to get the lowest priority group (4) at the bottom of the projection formula. Suppose after group priority assignments projection I is obtained. Interchange of the relative positions of two substituents gives the enantiomer. Two such interchanges returns the beginning configuration. Thus in the sequence below III is equivalent to I and structure III is readily seen to be (R).

The double interchange can be done in one operation, e.g.,}

2. Assign designations to the following:

3. Assign (R) or (S) absolute configurations to the following compounds:

(a) (R) (b) (R)

4. Assign (R) or (S) absolute configuration to the following compound.

(R). Isobutyl has higher priority that hexyl.

There is no set procedure for the manipulation of stereo formulas to allow the assignment of (R ) or (S). The method outlined above seems to be reliable for novices. After some experience you may fine others methods more convenient. Any chiral center which projects the (4) priority group away from the observer will allow the immediate reading of the other groups, in a clockwise sequence for (R) stereochemistry or a counter-clockwise sequence for (S) stereochemistry.

The inference of the above is that any chiral center which has the lowest priority group (4) toward the observer and the other groups in a clockwise sequence will be (S), etc.

Use whatever method or methods your feel comfortable with. Verify the above using a tetrahedral model with labels (1), (2), (3) and (4).

5. Give the complete name including stereochemical descriptor for the following compound.

(S)-2,2-Dimethyl-3-nonanol

6. Give the complete name including stereochemial descriptor for the following compound.

(R)-3,3-Dimethylcyclohexanol

Problem: Draw the projection formula for (S)-2-bromohexane.

Solution: Write out the groups attached to the chiral center and assign priorities.

Rewrite the groups on a standard projection for a (S) center.

7. Draw the projection formula for (S)-3-hexanamine.

8. Assign the configuration of the following compound:

(S)-1-Ethynyl-2-cyclohexen-1-ol

When a compound contains two or more chiral centers, locants are used in conjunction with stereochemical descriptors.

9. Give the complete name including stereochemical descriptors of the following compound.

(2S,3S)-2-Chloro-3-pentanol

For the sake of completeness several advanced topics in stereochemical nomenclature will now be presented. You may or may not wish to review this material depending on your own interest or the assignment by your instructor.

Sequence Rule 5

A missing substituent, i.e., a non-bonded electron pair, on a chiral heteroatom is regarded as being of zero atomic number and therefore ranks lower than H^.

Chiral nitrogen

Chiral sulfur

Some advanced examples of the use of R/S nomenclature:

Unknown absolute but known relative configuration:

Spoken as "R star, S star". It is arbitarily assumed that the lowest locant has the descriptor R *.

Other stereochemical descriptors are used for special systems. In bicyclic systems wherein each birdge contains at least one atom, e.g., [2.2.1], [2.2.2], [3.2.1], etc. systems, a substituent not on the main bridge is designated by the prefix exo- proceeding the locant when it is cis to the main bridge and by endo- when it is trans to the main bridge. The main bridge is chosen as follows (in order):

1. Bridges containing heteroatoms

2. Bridges containing fewer atoms

In steroids and in sugars when structures are written in the following "standard" orientations substituents above the "plane" are denoted as b, those below as a.

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Alkynes