Hydrogen thioether activation

In 2004, a series of other chiral thioether-phosphine ligands based on a cyclopropane backbone were evaluated in the rhodium-catalysed hydrogenation of a dehydroamino acid by Molander el al As shown in Scheme 8.2, even if these ligands were generally active, only moderate enantioselectivities of up to 47% ee were obtained. 

An unusual carbene-thioether hybrid ligand 174 was synthesized and applied in the rhodium-catalyzed asymmetric hydrogenation of dimethyl itaconate by Chung and co-workers however, the selectivity and activity were low (Table 27.7, entry 34) [135]. 

The addition of a phenylsulfoxide moiety to the end of the side chain markedly changes the activity of this class of compounds. This product, sulfinpyrazone (97-11), stimulates uric acid excretion, making it a valuable dmg for dealing with the elevated serum uric acid levels associated with gout. The compound is stiU one of the more important uricosuric agents available today. The starting ester (96-9) is available by alkylation of the dianion from ethyl malonate with 2-chloroethylphenyl thioether. Condensation with diphenylhydrazine (97-3) in the presence of a base then affords the pyrrazolodione (97-10). Oxidation of sulfur with a controlled amount of hydrogen peroxide leads to the sulfoxide and thus sulfinpyrazone (97-11) [107]. 

H atoms (H ) tend to abstract hydrogen atoms from C-H bonds, particularly if these are activated by neighboring functionalities such as sulfur atoms. The sulfur atom in thioethers was not usually considered as the primary target of H atom despite some, mostly recent, reports showing that bimolecular homolytic substitutions with H atom might occur with thioethers. Because these sulfur atoms are hypervalent, they can form adducts with H atoms. Radical chemistry studies on 1,3,5-trithiane (1,3,5-TT), performed by pulse radiolysis,... 

In fluid-solution systems, the plain hydrogenation of thiophenes to thioether products has been found to be catalyzed by various transition metal complexes surprisingly, none of these catalysts contains either molybdenum or tungsten, which are essential components of heterogeneous HDS catalysts [1 b]. Unpromoted M0S2, on the other hand, is quite active for the HDS of thioethers with no need of assistance by a late transition metal promoter [lb]. 

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