Asymmetric synthesis of a xanthine dehydrogenase inhibitor (S)-(−)-BOF-4272: Utility of chiral alkoxysulfonium salts

A practical synthetic method for a xanthine dehydrogenase inhibitor, (S)-(−)-BOF-4272, was established utilizing an asymmetric oxidation of diaryl sulfide BOF-4269. The oxidation of the sulfide with 1-chlorobenzotriazole carried out in the presence of 4-cyanopyridine and chiral 2-phenylcyclohexanol gave a high enantiomeric excess (73%ee). The sulfoxides in each enantiomerically pure form could be obtained by treating with alkaline hydrolysis or thermolysis of one the diastereomeric intermediate sulfonium salts (>99%de). Thus the transformation into the sulfoxides occur with virtually perfect inversion (alkaline hydrolysis) or retention (thermolysis). It is therefore possible to obtain the target sulfoxide, (S)-(−)-BOF-4272, from both the two diastereomeric sulfonium intermediates.