抄録
Sulfoxides are sometimes found in natural compounds and many important pharmaceutically active compounds such as omeprazole are composed of sulfoxide group. A sulfoxide can exist as an enantiomer because racemization between two enantiomers is generally very slow or impossible under the usual conditions. There are few method for determining the absolute configuration of chiral sulfoxide except for X-ray crystallography or synthetic approach. As NMR methods, aromatic solvent-induced shift (ASIS) and some chiral shift reagents such as 9-anthryl-1,1,1-trifluoroethanol, methoxyphenylacetic acid, and N-(3,5-dinitro-benzoyl)-α-phenylethylamine (Kagan's reagent) have been used for this purpose. However, the difference of the chemical shifts between two diastereomeric pairs is generally very small and sometimes nonsystematic. In this paper, we report the reliable method for elucidating the absolute stereochemistry of chiral sulfoxides by means of NMR spectroscopy. The new method consists of two major processes: (i) conversion of a chiral sulfoxide to a chiral sulfoximide with retention of the stereochemistry using mesitylsulfonylhydroxylamine (MSH), and (ii) coupling reaction of the chiral sulfoximide with (S)- and (R)-methoxyphenylacetic acid (MPA). MPA was selected as the chiral anisotropic reagent because the molecular model analysis revealed that the N-MPA-sulfoximide would exist in only one stable conformation. Several racemic and chiral sulfoxide were prepared by the known synthetic method such as the diacetone-D-glucose (DAG) method, and the sulfoxides were transferred by the two-step reactions into N-MPA-sulfoximides. The Δδ values for the protons were calculated according to the equation, Δδ=δ_<S-MPA>-δ_<R-MPA>. In all the examples, the systematic distribution of Δδ values were observed without exceptions, and the results obtained by the present method agreed with the known absolute configurations.
