How to Determine the R / S Configuration of a Chiral Center from a Fischer Projection

An easy way to find the R / S configuration of a molecule with more than one chiral center is with a Fischer projection. A Fischer projection is a convenient two-dimensional drawing that represents a three-dimensional molecule.

To make a Fischer projection, you view a chiral center so that two substituents are coming out of the plane at you, and two substituents are going back into the plane, as shown here. Then the chiral center becomes a cross on the Fischer projection. Every cross on a Fischer projection is a chiral center.

Fischer projections are convenient for comparing the stereochemistries of molecules that have many chiral centers. But these projections have their own sets of rules and conventions for how you can rotate and move them.

As shown in the figure below, the two main ways to rotate a Fischer projection are as follows:

• You can rotate a Fischer projection 180 degrees and retain the stereochemical configuration, but you cannot rotate a Fischer projection 90 degrees.

• You can rotate any three substituents on a Fischer projection while holding one substituent fixed and retain the stereochemical configuration.

Here’s how to determine the configuration of a chiral center drawn in a Fischer projection: First, you prioritize each of the substituents using the Cahn–Ingold–Prelog prioritizing scheme.

According to the Cahn–Ingold–Prelog prioritizing scheme, the highest priority goes to the substituent whose first atom has the highest atomic number. (For example, Br would be a higher priority than Cl, because Br has a larger atomic number.)

Then, you put the fourth priority substituent on the top, and draw a curve from the first- to the second- to the third-priority substituent. If the curve goes clockwise, the configuration is R; if the curve goes counterclockwise, the configuration is S.

To get the number-four priority substituent at the top of the Fischer projection, you have to use one of the two allowed moves diagramed in the second figure. (You can make a 180-degree rotation, or you can hold one substituent fixed and rotate the other three.) Two examples of the determination of the configuration from Fischer projections are shown here.