160 Essays in Biochemistry 



involve some form of complexing between the a groups and the asym- 

 metric E, differentiation of the a groups can still be expected. 



If the process consists in an attack of E on the central carbon 

 atom which replaces either a' or a", the transition states 7 (Villa or 

 VIII6, respectively) are not identical but related like diastereoisomers. 

 Hence the heights of the energy barriers separating the starting com- 

 pounds from the products as well as the energy contents of the latter 

 would be expected to differ for the substitution of a' and of a". 



If the reaction of the a groups is initiated by some combination of 

 E with the b group as in IXa, the steric relationship of a' to E is not 

 identical with that of a" to E nor will it become identical by any 

 rotation around a single bond as in 1X6. It is clear then that a 



sJX *%^' 



b b 



! ! 



I I 



l I 



c c 



IXa IX b 



variety of reasonable mechanisms can be conceived which do not 

 require a three-point attachment and which nevertheless permit the 

 differentiation of identical substituents. Although this is to be expected 

 if the optically active species E participates directly * in the steps 

 which alter the a group in Caabc, it must be noted that this differentia- 

 tion often is too small to be detected or too transitory to be preserved. 



Since the common feature of all these reactions is the diastereomeric 

 character of some intermediate or product, it seems justified to neglect 

 these mechanistic details and to seek the basis for the differentiation 

 of identical groups in some structural characteristic of the substrate. 

 To define it, the following rules have been proposed: 



1. Wilcox: 2 "In a molecule which has a plane of symmetry or a 

 point of symmetry, if one of the atoms which does not lie in any plane 



* This stipulation seems quite essential. If, for instance, the reaction can be 

 represented by an ideal unimolecular substitution 7 in the a group by E, the rate- 

 determining dissociation proceeds in the virtual absence of E and hence should 

 proceed with equal facility in the a' and a" group. Similarly, if E attacks b 

 changing it to the symmetric substituent d which subsequently in the absence 

 of E causes a secondary change affecting the a groups, no differentiation is to be 

 expected. 



