Intrinsic Asymmetry and Diastereotopism

The term "intrinsic asymmetry", as applied to the time-averaged anisochrony of geminal groups in systems of the type (R*)CU*V (where R* is a chiral perturbing group), is critically discussed against the background of symmetry criteria for chemical shift nonequivalence. It is concluded that continued use of the term is no longer justified. The symmetry require- ments for time-averaged anisochrony under conditions of equipopulation of conformers are extended to the general case of an n-fold barrier to internal rotation. Chemical shift nonequivalence of geminal methyl groups in a compound of the type XYZC- C=C-CH(CH& is demonstrated and the adequacy of the free rotation (windmilling) model for such a system is discussed. It is noted that for NMR purposes, the distinction between groups diastereotopic by internal and external comparison is more a matter of convenience than of principle. The structural criteria for magnetic shielding (or chemi- cal shift) equivalence (isochrony) and nonequivalence (ani- sochrony) of nuclei have previously been discussed in terms of the symmetry relationships between molecular subunitsS2 Against the backdrop of this analysis, the present paper ad- dresses the theme of "intrinsic asymmetry", which continues to be the subject of lively interest even though it has been under debate for 20 years.