The use of mid-points or average NMR chemical shifts in stereochemical assignments

A comparison of the mid-points or average chemical shifts of mirror-symmetrical spin patterns in the NMR spectra of structural isomers can be used in a straightforward manner to obtain stereochemical information. This result is anticipated from analysis of substituent contributions to chemical shifts and has been observed in a variety of chemical systems, especially cyclobutane derivatives, which comprise a group of compounds for which appreciable data is available and whose structure assignments have often entailed difficulty and even controversy. The method of mid-point comparison may also be useful for conformational analysis.