Pseudopeptidic sulfoxides: relative stability and absolute configuration of diastereomers

The relative stability in solution of diastereomeric pseudopeptidic sulfoxides initially designed as FKBP inhibitors is used to assign the absolute configuration at the sulfur atom. Decomposition is shown to occur via β-elimination of the corresponding sulfenic acid and alkene. Complementary studies including molecular mechanics, 1H NMR spectroscopy and optical rotation confirm that the (R)-isomer is the most stable, presumably due to non-bonded interactions favouring a low energy conformation where decomposition is precluded.