Pseudoasymmetry as a Means for Distinguishing Meso and dl Diastereomers

Meso and dl diastereomers of compounds containing two constitutionally equivalent chiral units can be distinguished by using NMR spectroscopy to demonstrate the creation of pseudoasymmetry. In suitable compounds, a new configurational unit, a unit of pseudoasymmetry, can be constructed in the meso diastereomer but not the dl diastereomer. Two examples are presented and analyzed, using cyclic and acyclic examples and featuring both a configurationally stable pseudoasymmetric center and a configurationally labile pseudoasymmetric axis. In the first example, a pseudoasymmetric center was introduced into cis-2,6-dimethylcyclohexanone by reduction to the carbinol, and the configurations of the two diastereomers were assigned on the basis of their NMR spectra. The corresponding trans ketone furnished only a single diastereomer. Chemical-shift nonequivalence in the benzyl ether of the -carbinol also permitted its assignment. In the second example, the 2,4-dinitrobenzenesulfenamides of meso- and -bisphenylethylamine were prepared. The sulfenamide bond in the meso sulfenamide is an axis of pseudoasymmetry, and the presence of two meso isomers is evident in the NMR spectrum. The free energy of activation at the coalescence temperature for rotation about the S-N bond in the dl sulfenamide (T_c = 91°; T_c = 19.6 kcal/mol) was intermediate between those for forward and reverse interconversions of the two meso diastereomers (T_c = 86°; Δ_c‡(forward) = 19.5 kcal/mol; Δ_c‡(reverse) = 20.5 kcal/mol), although the stereochemical descriptions of the processes associated with coalescence in the two cases are different.