R and S Configuration: R & S Nomenclature, Assigning R & S configurations, Cahn-Ingold-Prelog Rules
This is a newer and more systematic method of simplyfing absolute configuration to optically active compounds. R and S cofiguration was proposed by R.S.Chan, C.K.Ingold and V.Prelog and therefore, it is also called Cahn-Ingold-Prelog Rules or CIP rule.
Cahn-Ingold-Prelog system is based on the actual three dimensional or tetrahedral structure of the compound. In order to specify configuration about an assymetric carbon, the groups attached to assymetric carbon are first assign and order of priority determined by the sequence rule. If the tetrahedral model viewed from the direction opposite of the smallest atom (blue atom in the figure), then according to the sequence rule,
1. If the eye while moving from 1 → 2 → 3 travel in a clockwise or right hand direction, the configuration is designed as R (comes from a Latin word Rectus which means Right).
2. If the eye while moving from 1 → 2 → 3 travel in a counterclockwise or left hand direction, the configuration is designed as S (comes from a Latin word Sinister which means Left).
Note: In the given molecule, atoms attached to assymetric carbon is arranged in highest to lowest priority order as 1 > 2 > 3.
Sequence Rule to Assign R/S Configuration
1. The atoms or groups directly bonded to the assymetric carbon atom are arranged in order of decreasing atomic number and assigned priority 1,2,3,4 accordingly.
For example: I > Br > Cl > F > O > N > C > H.
2. When two or more groups have identical first atoms attached to asymmetric carbon, the priority order is determined by considering the atomic numbers of the second atoms and if the second atoms are identical the third atoms along the chain are examined.
For example: -CH2-CH2-CH3 > -CH2-CH3 > -CH3
3. If the first atoms of the groups have same substituents of higher atomic number, the one with more substituents takes priority.
For example: CHCl3 > CH3Cl
4. When isotopes of the same atom are attached to assymetric carbon, then priority is given to isotopes with higher atomic weights.
For example: 3H (tritium) > 2H (deuterium) > 1H (hydrogen).
5. When a doubly or triply bonded atom attached to assymetric carbon atom, then it is considered equivalent to two or three singly bonded atoms.
For example: >C=O considered as two oxygens are attached to carbon and two carbons are attached to oxygen, -C≡N considered as three nitrogens are attached to carbon and three carbons are attached to nitrogen.
Find out the R/S configuration in the given molecule.
Answwr: The priority order of the groups attached to the assymetric carbon is
OH > CHO > CH2OH > H
Applying the sequence rule to the glyceraldehyde, we find the configuration R as shown below.
Shorcuts For Assigning Absolute Configuration On Paper
According to the Cahn-Ingold-Prelog convention, when assigning absolute configuration to a chiral carbon the lowest priority group that's attached to that carbon must be pointing away from an observer. On paper, if the observer looking at the page, then the lowest priority group is pointing away from the observer, going behind the plane of the paper. In a 3D formula this is indicated thus:
When the formula is given as shown above, it's easy to assign configuration. Just assign priorities to the other three substituents and see if they are arranged clockwise or counterclockwise when the observer follows them in order of decreasing priorities. The carbon has the (S) configuration in the above molecule.
If the lowest priority group is not presented to us already positioned towards the back of the chiral carbon, then remember the following basic principle:
Every time any two substituents are exchanged, the opposite configuration results.
Case-1: If the lowest priority group is positioned in front of the chiral carbon we can still assign configuration by following the arrangement of the other three groups as given, but the configuration obtain will be the opposite of the actual one.
With the lowest priority group positioned in the front rather than towards the back, the central carbon appears to have the (R) configuration. The actual configuration is therefore, (S). This is best seen when we rotate the molecule until the H atom is in the correct orientation.
Case-2: If the lowest priority group is positioned on the plane of the paper, we can momentarily exchange it with whatever group happens to be positioned in the back, then assign configuration, then reverse it.
Assign Absolute Configuration in Cyclic Molecules
Cyclic molecules are represented on paper in such a way that the ring atoms are all lying on the plane of the paper, and substituents are either coming out of the paper towards the front or towards the back. It is therefore easy to assign configuration to any chiral centers forming part of the ring, since the lowest priority substituent will be either pointing to the front or to the back. However, always make sure there is in fact a chiral center present. The fact that a 3D representation is given does not necessarily mean there is a chiral center in the molecule.
Assign Absolute Configuration in Fischer Formulas
The key points to keep in mind regarding Fischer projection formulas are:
1. Horizontal lines represent bonds to the chiral carbon that are coming out of the plane of the paper towards the front, whereas vertical lines represent bonds going behind the plane of the paper towards the back. Thus, Fischer formulas are easily translated into bow tie formulas, which are 3-D formulas.
2. The lowest priority group bonded to the chiral carbon must always be shown as a horizontal bond.
The process of assigning (R) or (S) configuration to the chiral carbon is the same as discussed before, but since the lowest priority group is pointing towards the front, the configuration obtained directly from a Fischer formula is the opposite of the actual one.
The order of priorities follows a clockwise direction in the Fischer formula. Therefore the actual configuration of this molecule is (S).
Once we know the actual configuration, we can represent the molecule in any of several possible ways using 3-D formulas. Thus the formulas shown below all represent the same molecule as given above in Fischer projection form. That is to say, all have the (S) configuration at the central carbon.
Assign Configuration to Conformationally Mobile Systems
This is probably one of the trickiest situations to deal with, especially when the molecule is shown to us in conformations such as a cyclohexane chair, or represented by Newman projections. It is a good idea in these cases to work with models, because one cannot help but to turn the molecule around until the lowest priority groups are positioned where they should be, and the priorities of the groups attached to the chiral centers can be clearly seen.
In the case of cyclohexane chairs and other rings, it’s a good idea to flatten the ring and position it on the plane of the paper, with the lowest priority groups pointing towards the back when possible.
In the case of Newman projections, it helps to rotate one of the carbons around the C–C bond under consideration until as many similar groups as possible are aligned (eclipsing each other), then rotate the structure sideways to obtain a side view, rather than a projection, then assign priorities and configuration.
