Sulfoxide, enantioselective synthesis, from sulfide

Preparation of various enantiomerically pure sulfoxides by oxidation of sulfides seems feasible in the cases where asymmetric synthesis occurs with ee s in the range of 90% giving crystalline products which can usually be recrystallized up to 100% ee. Aryl methyl sulfides usually give excellent enantioselectivity during oxidation and are good candidates for the present procedure. For example, we have shown on a 10-mmol scale that optically pure (S)-(-)-methyl phenyl sulfoxide [a]p -146 (acetone, o 1) could be obtained in 76% yield after oxidation with cumene hydroperoxide followed by flash chromatographic purification on silica gel and recrystallizations at low temperature in a mixed solvent (ether-pentane). Similarly (S)-(-)-methyl o-methoxyphenyl sulfoxide, [a]p -339 (acetone, o 1.5 100% ee measured by HPLC), was obtained in 80% yield by recrystallizations from hexane. 

The typical S-oxidation with BVMOs allows the formation of chiral sulfoxides from organic sulfides. This oxidation has received much interest in organic chemistry due to its use in the synthesis of enantiomerically enriched materials as chiral auxiliaries or directly as biologically active ingredients. This reaction has been studied extensively with CHMO from Adnetohacter showing high enantioselectivi-ties in the sulfoxidation of alkyl aryl sulfides, disulfides, dialkyl sulfides, and cychc and acyclic 1,3-dithioacetals [90]. CHMO also catalyzes the enantioselective oxida-hon of organic cyclic sulfites to sulfates [91]. 

A platform had been created from which it was felt that the enantioselective sulfoxide synthesis could be developed into a process that would match logistical as well as quality requirements. However, it is important to stress that other variations of the titanium-catalyzed approach had been concomitantly identified but the decision was taken to focus solely on the present option. One of the most important and challenging aspects in this regard was to demonstrate how the oxidation step could be fitted into the existing manufacture of the prochiral sulfide (pyrmetazole) and, if not, what changes or modifications would be needed. This... 

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