172 Essays in Biochemistry- 



available if we recognize that the motions to be used for the super- 

 position of identical substituents include not only those applicable 

 to rigid bodies but also all internal motions of nuclei that proceed 

 readily under reaction conditions. Obviously there is nothing in the 

 derivation of rule 4 which would preclude such an interpretation of 

 permissible motions.* 



As set forth above, numerous mechanisms can be conceived to explain 

 the differentiation of identical substituents in suitably constituted 

 molecules. The efficacy of these mechanisms, however, is often quite 

 small, and the question arises whether any process besides three-point 

 attachment to an asymmetric reagent can be expected to lead to a 

 differentiation of a high order. Studies of relatively simple systems 

 afford at least a tentative answer to this question. Only a few demon- 

 strations of discrimination of identical substituents in symmetric mole- 

 cules have been recorded in which an asymmetric reagent of known 

 structure is employed. Although these experiments have clearly dem- 

 onstrated the occurrence of the phenomenon, they have left some doubt 

 as to the exact role of the asymmetric agent in the differentiation. 4 

 The example reported most recently 4 appears to be no exception. 8 In 

 order to observe the differentiating powers of thermodynamic and 

 kinetic factors separately, it seems best, therefore, to turn to related 

 phenomena. If a racemic mixture of a compound containing a labile 

 asymmetric center is permitted to interact with an optically active 

 reagent, the 1:1 proportion of optical antipodes is frequently dis- 

 turbed. 1 The extent of such asymmetric transformations can be quite 

 substantial even in homogeneous systems (62% excess in the case of 

 chlorobromomethanesulfonic acid as a salt of ( — ) -hydroxyhydrinda- 

 mine), but essentially complete conversion to one of the diastereo- 

 isomers occurred only if the transformation was aided by selective 

 precipitation. Although the asymmetry so induced is frequently lost 

 again by racemization after removal of the optically active reagent, 

 such transformations can be looked upon as a demonstration of the 

 efficacy which thermodynamic factors can possess in asymmetric proc- 

 esses. 



Good examples for kinetic control of asymmetric processes can be 



* Although the definition of symmetry number has also been adjusted to meet 

 the problem of internal rotation (ref. 13, p. 510), such symmetry numbers are 

 no longer applicable to our problem. For example, n-butane which has a "rigid 

 symmetry number" of two and a "free-rotation symmetry number" of 18 contains 

 six equivalent primary hydrogens but two non-equivalent pairs of secondary 

 hydrogen atoms. 



