Sulfide enantioselective conversion

The enantioselective oxidation with Ti-tartrate complexes has proven to have further important uses in different oxidation processes. Thus as an example, Kagan has reported that these oxidation conditions can be utilized in the enantioselective conversion of sulfides into sulfoxides (Equation 13) [83],... 

Hoft reported about the kinetic resolution of THPO (16b) by acylation catalyzed by different lipases (equation 12) °. Using lipases from Pseudomonas fluorescens, only low ee values were obtained even at high conversions of the hydroperoxide (best result after 96 hours with lipase PS conversion of 83% and ee of 37%). Better results were achieved by the same authors using pancreatin as a catalyst. With this lipase an ee of 96% could be obtained but only at high conversions (85%), so that the enantiomerically enriched (5 )-16b was isolated in poor yields (<20%). Unfortunately, this procedure was limited to secondary hydroperoxides. With tertiary 1-methyl-1-phenylpropyl hydroperoxide (17a) or 1-cyclohexyl-1-phenylethyl hydroperoxide (17b) no reaction was observed. The kinetic resolution of racemic hydroperoxides can also be achieved by chloroperoxidase (CPO) or Coprinus peroxidase (CiP) catalyzed enantioselective sulfoxidation of prochiral sulfides 22 with a racemic mixmre of chiral hydroperoxides. In 1992, Wong and coworkers and later Hoft and coworkers in 1995 ° investigated the CPO-catalyzed sulfoxidation with several chiral racemic hydroperoxides while the CiP-catalyzed kinetic resolution of phenylethyl hydroperoxide 16a was reported by Adam and coworkers (equation 13). The results are summarized in Table 4. 

With substrates 16b and 17a, Hoft and coworkers observed only low ee values of up to 4% for the hydroperoxides. On the other hand, phenyl ethyl hydroperoxide (16a) could be isolated in high enantiomeric excess of >99% from the CPO-catalyzed reaction. The observed enantioselectivities of the sulfoxides varied, depending on the conversion of the sulfide and the hydroperoxide used, being highest with 16a (92% ee). Unfortunately, the CPO-catalyzed resolution of chiral hydroperoxides is difficult on a preparative scale because of the high dilution necessary (0.5ttmolmL ). In the CiP-catalyzed kinetic resolution of 16a better results were obtained compared to the CPO-catalyzed reaction (see Table 5). 

Enantiopure 2,2,5,5-tetramethyl-3,4-hexanediol was prepared by Yamanoi and Imamoto [46]. A combination of Ti(0-i-Pr)4 with this diol (1 2) gives a chiral catalyst for sulfide oxidation with cumyl hydroperoxide in the presence of 4A molecular sieves in toluene. At -20°C p-tolyl methyl sulfoxide (95% ee) was obtained in 42% yield together with 40% sulfone, A kinetic resolution increased, to some extent, the enantiomeric excess of the product, that is, at lower conversion (20% yield) the enantiopurity of the resulting sulfoxide was only 40% ee. This catalytic system is ineffective for the enantioselective oxidation of dialkyl sulfides. 

Choline dihydrogenphosphate, choline acetate and choline citrate (Scheme 4) show improved properties, with respect common molecular solvents and imidazolium based ILs, also in the chloroperoxidase-catalyzed reactions." In the presence of these cosolvents (up to 70%) the conversion of methyl phenyl sulfide to the corresponding sulfoxide, leads to satisfactory yields and very good enantioselectivities. In addition, over-oxidation of the sulfoxide to the sulfone is not observed. 

At atmospheric pressure, the conversion of sterically hindered primary and secondary alcohols into the corresponding phenyl sulfide derivatives with a BusP-PhSSPh system occurs in low yields (0-56%) at 1.0 GPa pressure, the same reactions have given a 65-100% yield.Thus, this reaction has been used in the seven-step enantioselective synthesis of (-)-solenopsin... 

Enantioselective aldol reactions. Enders et ul. have reported a regiospecific and enantioselective aldol synthesis. The method involves conversion of a methyl ketone into the chiral hydrazone 2, a-metalation, reaction with a carbonyl compound, and silylation to form a doubly protected ketol 3. The chiral ketols 4 are obtained by oxidative hydrolysis with H2O2 (30%) at pH 7 or by sensitized photooxidation in THF followed by reduction with dimethyl sulfide. Optical yields are 30-60%. The absolute configuration of the ketols is not known at present. 

The Coprinus cinerem peroxidase (Cip) was later used in ionic liquid [BMImJPFfi as a reaction medium in peroxidase-catalyzed oxidation of sulfides to sulfoxides in high enantioselectivity (92% ee) [84]. However the reaction was very slow (14% conversion after 16h). Glucose oxidase from Asper llus niger was employed to generate H2O2 from O2. 

A change of the sulfide loading from stoichiometric to catalytic amounts (20 mol%) reduced yields and increased reaction times. The diastereoselectivity was very poor, enantioselectivities for the chiral organocatalyst 228 were not reported. Attempts to extend the reaction to other bromides were unsuccessful. Saito et al. utilized the same one pot protocol with another chiral catalyst (289) in the presence of an excess of aryl halides and base. He achieved moderate to excellent conversions. Use of dry acetonitrile prevented imine hydrolysis and enantioselectivities became good to excellent (Scheme 7.47) [172]. 

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