Tolyl methyl sulfide oxidation

Asymmetric sulfide oxidations are reported using oxaziridines other than A -sulfonyloxaziridines, but it is necessary to use a protic acid or Lewis acid to increase their reactivity. For example, -tolyl methyl sulfide 152 with bicyclic oxaziridine 153 in the presence of TFA gave the (A)-sulfoxide 154 in 50% yield and 42% ee in 24 h <1999T155>. It is interesting to note that use of MsOH resulted in much faster reaction with the oxidation complete in less than a minute. Similarly, sulfide 155 with chiral oxaziridine 156 in the presence of zinc chloride afforded sulfoxide 157 in 30% yield and 55% ee <2005JOC301>. 

Uemura described use of a Ti(OiPr)4/(i )-BINOL complex for the oxidation of alkyl aryl sulfides with aqueous ferf-butyl hydroperoxide as stoichiometric oxidant [22]. At room temperature p-tolyl methyl sulfide was converted into the corresponding sulfoxide with 96% ee in 44% yield with as little as 5 mol % of the chiral ligand. The reaction is insensitive to air, while the presence of water seems to be essential for the formation of the catalytically active species, long catalyst lifetime, and high asymmetric induction. The authors observed a large positive non-linear effect which indicates that the actual catalyst consists of a titanium species with more than one (K)-BINOL ligand (11) coordinated to the metal. 

The reaction is proposed to proceed via an intermediary copper nitrenoid species as known from the related copper-catalyzed aziridination of olefins [54]. A tentative transition state model for the stereochemical outcome of the oxidation ofp-tolyl methyl sulfide was suggested in which the approach of the sulfide was directed by a n-K interaction between the phenyl ring of ligand 30 and the aryl group of the sulfide. However, to date the exact mechanism remains unclear. 

In 1986, we discovered the first three cases of nonlinear effects in asymmetric synthesis the Shaipless epoxidation of geraniol ((+)-NLE), the asymmetric oxidation of p-tolyl methyl sulfide by our titanium reagent ((-)-NLE), and the proline catalyzed asymmetric aldolization of a triketone ( (-)-NLE). The mechanism of the last reaction was studied by Agami et al and found to be second-order with respect to proline. ... 

The hydrogen peroxide-mediated oxidation of p-tolyl methyl sulfide with chiral iminium salt 20 (Figure 19.9), reported in 1993, gives a 32% ee [81]. The use of chiral flavinium salt catalysts afforded a 65% ee for the same transformation [119]. 

A further catalytic method for asymmetric sulfoxidation of aryl alkyl sulfides was reported by Adam s group, who utilized secondary hydroperoxides 16a, 161 and 191b as oxidants and asymmetric inductors (Scheme 114) . This titanium-catalyzed oxidation reaction by (S)-l-phenylethyl hydroperoxide 16a at —20°C in CCI4 afforded good to high enantiomeric excesses for methyl phenyl and p-tolyl alkyl sulfides ee up to 80%). Detailed mechanistic studies showed that the enantioselectivity of the sulfide oxidation results from a combination of a rather low asymmetric induction in the sulfoxidation ee <20%) followed by a kinetic resolution of the sulfoxide by further oxidation to the sulfone... 

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. 

The original Sharpless reagent, a mixture of tetraisopropyl orthotitan-ate, (i ,/ )-diethyl tartrate, and tert-butyl hydroperoxide in the ratio 1 1 2 in dry dichloromethane or 1,2-dichloroethane [1025, is modified by adding 1 mol of water 224, 1029]. Such a reagent gives higher enantiomeric excesses. Of many sulfide oxidations that have been carried out, the conversion of methyl p-tolyl sulfide into the sulfoxide is shown in equation 565. 

Uemura et al. found that the combination Ti(OPr%/binaphthol/water in ratio 1 2 >10 acts as a catalyst for oxidation of aryl methyl sulfides into the corresponding sulfoxides by Bu OOH (see also Section 1.4.1) [159]. A mechanistic study showed that the titanium complex was a sulfoxidation catalyst (initial ee -50%) as well as a catalyst for the overoxidation into sulfones, with an enhancement of the ee of the residual sulfoxides (because the minor sulfoxide enantiomer is preferentially oxidized). In a subsequent paper, the authors reported the kinetic resolution of racemic aryl methyl sulfoxides by the same catalyst [160]. A stereoselectivity factor s of 2.6 was calculated for the kinetic resolution of racemic methyl p-tolyl sulfoxide. For example, methyl p-tolyl sulfoxide (<99% ee) could be recovered from oxidation at about 75% conversion. Using partially resolved l,l -binaphthol, a positive nonlinear effect was established. 

Ghiral flavins have been used to obtain an asymmetric sulfoxidation with H2O2 as the oxidant [45a, 52]. Flavin 27, with planar chirality, was used to oxidize different aryl methyl sulfides with 35% H2O2. The hydrogen peroxide was added slowly over 5 days at —20°C to the substrate and the catalyst. The best result was obtained with the p-tolyl derivative, which gave 65% ee (Eq. (8.12)). 

The use of (S,S)-l,2-bis- butyl-l,2-ethanediol (S,S)-30) in the titanium-catalyzed oxidation of various aryl methyl sulfides by cumene hydroperoxide afforded sulfoxides in ees up to 95% (Scheme 8.5) [68[. Interestingly, the authors observed that the ee of the sulfoxide increased with the reaction time, indicating a kinetic resolution of the sulfoxide product. A control experiment with racemic p-tolyl sulfoxide showed that the (i )-enantiomer is oxidized to sulfone three times faster than the (S)-enantiomer by the catalytic system employed. For this reason, the yields of the chiral sulfoxides are moderate and in the range of 40-50%. 

Imamoto and Koto131 prepared some interesting chiral oxidants (104) by the reaction of iodosyl benzene with tartaric anhydride. Methyl p-tolyl sulfide (105) was oxidized by 104c to the sulfoxide in 80% yield with 40% e.e. Methyl p-tolyl, o-tolyl and o-anisyl sulfides (105-107) were oxidized by 104a to their sulfoxides with the enantiomeric purities shown. 

Komori and Nonaka132,133 electrochemically oxidized methyl, isopropyl, n-butyl, isobutyl, r-butyl and cyclohexyl phenyl sulfides (108) and cyclohexyl p-tolyl sulfide (109) to their sulfoxides using a variety of polyamino acid-coated electrodes to obtain the range of e.e. values shown in parentheses. The highest enantiomeric purities were obtained using an electrode doubly coated with polypyrrole and poly(L-valine), an electrode which also proved the most durable of those prepared. 

Of several procedures for the stereoselective oxidation of sulfides using organometallic complexes, two adaptations of Kagan s original process have gained prominence. In the first method the diol (36) is reacted with Ti(0 Pr)4 to form the catalyst. With cumyl hydroperoxide as the stoichiometric oxidant, methyl para-tolyl sulfide was converted into the optically active sulfoxide in 42 % yield (98 % ee)[109]. 

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