Assigning Absolute Configuration

The Cahn-Ingold-Prelog R/S System

The rules for assignment of priorities in order to assign absolute configuration are based on the same set of rules which have been used previously for assigning E and Z stereochemistry. The procedure is fairly straightforward for simple compounds; first, you assign priorities to the groups attached around the chiral center. Next, you rotate the molecule so that the lowest priority group is pointing towards the back (away from you). Finally, you examine the remaining group priorities and determine if they are now arranged so that the priority decreases clockwise (R, for rectus) or counterclockwise (S, for sinister).

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These rules are restated below, with examples:

Sequence priorities to the four substituents are assigned by  looking at the atoms attached directly to the chiral center.

1. The immediate substituent atom with higher mass number  gets  higher priority. 

2. Different isotopes of the same element are assigned a priority according to their mass number.

3. If two substituents have the same immediate substituent atom,  then the atoms are evaluated evaluate  progressively further away from the chiral center until a difference is found. i.e. If a decision regarding priority cannot be reached using Rule #1, compare the atomic numbers of the second atoms in each substituent, then the third, etc., until a difference is found.

   

4.  Double or triple bonded substituents , are treated as an equivalent set of single-bonded atoms.

            

Once the priorities have been assigned, rotate the molecule in space so that the lowest priority group is pointing back. Connect the three remaining groups in order of decreasing priority and examine the direction of the resulting rotation. Rotation which is clockwise is termed R (rectus; right) and rotation which is counterclockwise is termed S (sinister; left).

     

While discussing optical isomerism, we must distinguish between relative and absolute configuration (arrangement of atoms or groups) about the asymmetric carbon atom. Let us consider a pair of enantiomers, say (+)^- and (–)^- lactic acid.

We know that they differ from one another in the direction in which they rotate the plane of polarised light. In other words, we know their relative configuration in the sense that one is of opposite configuration to the other. But we have no knowledge of the absolute configuration of the either isomer. That is, we cannot tell as to which of the two possible configuration corresponds to (+)  - acid and which to the (–)  - acid.

D and L System

The sign of rotation of plane-polarized light by an enantiomer cannot be easily related to either its absolute or relative configuration. Compounds with similar configuration at the asymmetric carbon atom may have opposite sign of rotations and compounds with different configuration may have same sign of rotation. Thus d-lactic acid with a specific rotation + 3.82^o gives l-methyl lactate with a specific rotation -8.25°, although the configuration (or arrangement) about the asymmetric carbon atom remains the same during the change

Obviously there appears to be no relation between configuration and sign of rotation. Thus D-L-system has been used to specify the configuration at the asymmetric carbon atom. In this system, the configuration of an enantiomer is related to a standard, glyceraldehyde. The two forms of glyceraldehyde were arbitrarily assigned the absolute configurations as shown below.

If the configuration at the asymmetric carbon atom of a compound can be related to D (+)-glyceraldehyde, it belongs to D-series; and if it can be related to L(–)-glyceraldehyde, the compound belongs to L-series. Thus many of the naturally occurring a-amino acids have been correlated with glyceraldehyde by chemical transformations. For example, natural alanine (2-aminopropanoic acid) has been related to L(+)-lactic acid which is related to L(–)-glyceraldehyde. Alanine, therefore, belongs to the L-series. In general, the absolute configuration of a substituent (X) at the asymmetric centre is specified by writing the projection formula with the carbon chain vertical and the lowest number carbon at the top. The D configuration is then the one that has the substituent 'X' on the bond extending to the 'right' of the asymmetric carbon, whereas the L configuration has the substituent 'X' on the 'left'. Thus,

When there are several asymmetric carbon atoms in a molecule, the configuration at one centre is usually related directly or indirectly to glyceraldehyde, and the configurations at the natural (+)-glucose there are four asymmetric centres (marked by asterisk). By convention for sugars, the configuration of the highest numbered asymmetric carbon is referred to glyceraldehyde to determine the overall configuration of the molecule. For glucose, this atom is C–5 and, therefore, OH on it is to the right. Hence the naturally occurring glucose belongs to the D-series and is named as D-glucose.

However, the above system of nomenclature based on Fischer projection formulae, has certain disadvantages. Firstly before a name can be assigned to a compound, we must specify how its projection formula is oriented.

Secondly, sometimes the two asymmetric carbon atoms having the same kind of arrangements of substituents are assigned opposite configurational symbols. Thus for (–)-2, 3-butanediol we have

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