A Simple Method for Specifying the R/S Configuration about a Chiral Center John P. ldoux The University of Central Florida. Orlando, FL 32816 The most widely accepted method for specifying the configuration about a chiral center is the RIS system. In order to apply this system, one first establishes the priority sequence (based on the Cahn-Ingold-Prelog sequence rules) for the atoms or groups of atoms attached to the chiral center. The molecule is then viewed with a three-dimensional physical model or is drawn or mentally visualized as a (pseudo) three-dimensional representation in such a way that the group of lowest priority is directed away from the observer. The arraneement of the remainine erouDs is then ohserved in order to specify the R or S config&&ion; That is, if one must move in a clockwise direction in ~roceedinefrom the erouD of highest priority to the group-of secondvhighest priority, the configuration is specified R (for rectus, from the Latin for right); counterclockwise movement is specified S (for sinister, from the Latin for left). If one views the molecule with a three-dimensional physical model, there is little difficulty in assigning the correct configuration. However, some individnali, pnr~icularlystudents being exposed for the first timt. cn stereochemical considrrations, often encounter difficulty in the absence of a three-dimensional nhvsical model when required to draw or mentally visualize the proper arrangement for specifying configuration. An extremely simple method for specifying the RIS configuration about a chiral center which does not require the use of a three-dimensional physical model or the mental visualization of the molecule or the memorization of a recently reported' arbitrary numher system is dehelow:2 scribed ~ ~ ~ ~ ~ (1) Write a Fischer projection for the enantiomer whose example, consider one of configuration is to be specified. the enantiomers of lactic acid (2-hydroxypropanoic acid) in the Fischer projection I.
."
~~
~
~~
~~
~~~~
~
or
FH3
1
(2) Assign the priority sequence for thegroups attached to the chiral center based on the Cahn-lngold-Prelog sequence rules. For I the priority sequence is OH > COOH > CH3 > H (3) Rewrite the Fischer projection so that the group of lowest priority is in the lowest vertical position and then specify the configuration as R or S in the usual manner. In order to obtain a rewritten Fischer projection with the
same configuration as the original projection, an even numher of group interchanges is performed. For example, interchanging the H and OH of I (one interchange) and then the COOH and CH3 of I (a second interchange) gives 1'. HoJZH8
H I'
For I' (and thus I), the configuration about the chiral center is R since one must move in a clockwise direction in proceeding from the group of highest priority (OH) to the group of second highest priority (COOH). Since by convention the vertical groups of a Fischer projection point into and behind the plalie of the paper and horizontal groups point forward and out of the plane, an even numher of group interchanges for a Fischer projection as described above in step (3) is the equivalent of rotating a three-dimensional physical model of the molecule so that the group of lowest priority is directed away from the ohsewer. Thus, when using the group interchange method in order to obtain a rewritten Fischer projection with the same configuration as the original projection, it is immaterial which groups are interchanged so long as only an even numher of interchanges are executed3 and the group of lowest priority ends up in the lowest vertical position in the rewritten projection. For example, interchanging the H and OH of I and then either the OH and CH3 or the OH and COOH of I gives I" and I"', respectively. I" and I"', like I' (and thus I) are R configuration representations. OH H,c+cooH H I"
How&H H I,,'
' Dietzel, R. A., J. CHEM.EOUC.,56, 451 (1979).
The basis for the method described here was first alluded to in Eliel, E. L. "Stereochernisby of Carbon Compounds," McQaw-Hill, New Yolk. 196% p. 92. While at least one other advanced treatise on stereochemistry has made reference to this method (Natta, G.; Farina, M. "Stereochemistry," Harper & Row: New York, 1972; p. 241), it has not been described in detail in either the chemical education literature or in currently popular undergraduate organic textbooks. An odd number of interchanges is, of course, the equivalent of inverting the original configuration.
Volume 59
Number 7 July 1982
553
