Rotamers or Diastereomers? An Overlooked NMR Solution

The existence of rotamers in a solution of analyte complicates H-1 NMR analysis, especially when the presence of diastereomers is also possible. Organic chemists have often responded to this problem by conducting variable-temperature (VT) NMR experiments, changing NMR solvents, or adding complexing agents. Here, with specific examples, we illustrate the use of simple yet widely overlooked chemical-exchange NMR experiments which allow the nonintrusive rapid distinguishment of rapidly equilibrating small molecules such as rotamers from nonequilibrating diastereomers.