0. Cori University of Chile Faculty of Chemical Sciences Casilla 233, Santiago, Chile
Complementary Rules to Define R or S Configuration Viewing molecules from any side
The rules to specify the configuration of a chiral assembly have been explicitly stated by Cahn, Ingold, and Prelog.l,z Correct assignment of structure requires that the chiral atom should be placed in such a way that the substituent with the lowest sequence order points away from the reader ("steering wheel" model). Application of the sequence rules',2 may require rewriting every formula to conform to the "steering wheel" model. This may be awkward or time consuming in group discussions of molecules having more than one chiral center. The inversion of configuration of compounds formed in the biosynthesis of isoprenoids from mevalonic acid stereospecifically labeled with deuterium or tritium3 has been a typical case. The following complementary rules allow the application of the sequence rules directly on any formula, as written on the blackboard with the usual conventions of molecular per~pective.~ The sequence order of the four substituents on the chiral carbon atom will be 1 > 2 > 3 > 4. Substituent number 4 is the lowest ranking in the sequence rules.' If reference is made to substituents 2 or 4 (even numbered) and they are drawn pointing away from the reader, then the Cahn-Ingold-Prelog rules apply without change ( A and B of figure). If substituents 1 or 3 (odd numbered) are taken as reference and point away from the reader (C and D of figure), then a clockwise sequence of substituents should be designated as S and an anticlockwise order as R (Reverse Cahn's rule). 1 CAHN, R. S., I N ~ O LC.DK., , AND PREWG, V., h'zpe~ientia,7, XI -- (lQ5fil. ~ - --,~. a BENTLEY, R., "MolecuI~~. Assymetry in Biology," Academic Press, NewYork, 1970, Vol. I, p. 49. S P o ~ ~ bG., x ,AND CORNFORTH, J. W., Biochem. J., 101, 553
(1966).
Conversely, if substituents point towards the reader (inverted "steering wheel"), then the above rules are reversed again, i.e., with substituents 1 or 3 pointing towards the reader Cahn's rules are applied as usual, and nith substituents 2 and 4 pointing towards the reader, a clockwise arrangement denotes the S and an anticlockwise arrangement the R structure. See the table for summary of this procedure. The rationale of these complements is closely related to the rules used by Cahn, Ingold, and Prelog to obtain the R or S configuration from Fischer's projection formulas. Any single change on the spatial orientation of substituents implies an inversion, whereas a double change restores the original one.' This may also be applied to the substituent defining the position of the atom in space, and thus substituting 4 by 3 or 1 implies a single change, whereas substituting 4 by 2 implies a double changc. Summary of Applications of Complementary Rules A " . " . . "
substituent "Steering wheel" model "Inverted steering wheel" model
2 or 4 1 or 3 1 or 3 2 or 4
Rule application Cahn's rule Reverse Cahn's rule Cahn's mle Reverse Cahn's rule
Illustration of the use of the complementary rules for the four pOIIble orientations d subrtituenb.
Volume 49, Number 7, July 1972
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