Diastereoselective oxidation sulfides

When a prochiral sulfide is submitted to the oxidation by DMD or TFD, the corresponding racemic sulfoxide is produced, whereas in the case of a chiral sulfide, diastereoselective oxidation is feasible. For example, a good diastereoselectivity was obtained with the chiral cyclic disulfide in equation 21. ... 

Most reports on diastereoselective oxidation of sulfides are substrate-directed. Diastereoselectivity has been achieved by either steric- or neighboring-group participation.21 Incipient hydrogen bonding between the substrate hydroxyl group and the incoming percarboxylic acid has been evoked to explain the high diastereoselectivity observed in the oxidation of 10-exo-hydroxy-bornyl- derivatives 7 and 9 (Scheme 1). The oxidation of 9 with m-CPBA in MeOH occurs without stereoselectivity. 

Chloroperbenzoic acid (MCPBA) has been frequently applied to sulfide oxidation (Figure 3.96). MCPBA has been the oxidant of choice for the diastereoselective oxidation of 2-exo-hydroxynorbornyl systems containing a sulfide group in the 10 position and a diastereomeric excess (d.e.) of 80-90% is obtained. However, if the hydroxide function is protected as the ether, the d.e. drops to 30%.387 388... 

Figure 3.99 Diastereoselective oxidation of sulfides using a Mo02(acac) JTBHP system.

Iron porphyrin catalysts with TBHP have been used for the diastereoselective oxidation of sulfides affording up to 46% d.e.408 A series of manganese(salen) catalysts with hydrogen peroxide has been employed for the oxidation of aralkyl sulfides in 34-70% d.e. and 80-90% yield. The best catalyst was derived from enantiomerically pure trans-1,2-diaminocyclohexane (Figure 3.101).409... 

Figure 3.100 Diastereoselective oxidation of sulfides to sulfoxides using a VO(acac)2l TBHP system.

Figure 3.101 Manganese salen catalyst for diastereoselective oxidation of sulfides with hydrogen peroxide.

Since the first report in 1960, many procedures have been reported for the synthesis of optically pure sulfoxides by chemical oxidation of sulfides. Typical examples are as follows (i) the oxidation of achiral sulfides by chiral peroxy acids,(ii) oxidation by TBHP in chiral solvents or in the presence of chiral catalysts, and (iii) diastereoselective oxidation of sulfides containing another chiral center. Similar methodologies have been reported using other oxidants such as organic... 

The high degree of diastereoselection in the oxidation of chiral ferrocenyl vinyl selenides was supported by the oxidation of the chiral p-tolyl ferrocenyl sulfide, instead of the selenide, with MCPBA at low temperature. Thus, an almost complete diastereoselective oxidation occurred either at - 20 °C or - 78 °C to give the corresponding chiral sulfoxide (Scheme 11). On the other hand, the oxidation of p-tolyl 1 -(M,M-dimethylamino)ethylphenyl sulfide with MCPBA afforded... 

Scheme 1.16 Examples of kinetic resolution of a racemic sulfide by asymmetric oxidation, or of resolution by combination with a chiral auxiliary and subsequent diastereoselective oxidation...

CHMO.. has been used in the diastereoselective oxidation of different p-hydroxy sulfides to the corresponding chiral p-hydroxy sulfoxides. Chiral p-hydroxy sulfoxides represent interesting compounds used as chiral auxiliaries in asymmetric synthesis, asymmetric ligands, or as building blocks for the synthesis of cyclic sulfides, benzoxathiepines, allylic alcohols, or leukotrienes [27]. The sulfoxidation of these substrates is a kinetic resolution, in which both the sulfide and the sulfoxide can be obtained in chiral form. Oxidation of the cyclohexyl derivative (Table 6.1, entry 2) by a semipurified preparation of in the presence of the enzymatic... 

Modena and colleagues47 have developed use of some chiral, non-racemic terpene alcohols as directing groups for highly diastereoselective m-chloroperbenzoic oxidation of sulfides into sulfoxides. Specifically the isobornyl vinylic sulfides 8 undergo hydroxyl-directed oxidation to give a 9 1 ratio of diastereomeric sulfoxides (equation 11). 

Scheme 8 summarizes the introduction of the missing carbon atoms and the diastereoselective epoxidation of the C /C double bond using a Sharpless asymmetric epoxidation (SAE) of the allylic alcohol 64. The primary alcohol 62 was converted into the aldehyde 63 which served as the starting material for a Horner-Wadsworth-Emmons (HWE) reaction to afford an E-configured tri-substituted double bond. The next steps introduced the sulfone moiety via a Mukaiyama redox condensation and a subsequent sulfide to sulfone oxidation. The sequence toward the allylic alcohol 64 was com-... 

V(V), Mo(VI) and Ti(IV) derivatives proved to be both effective and selective in the oxidation of sulfides with alkyl hydroperoxides324. As for H2O2, vanadium is at least twofold more efficient than molybdenum in oxidation and much more selective, as proved by the data obtained with the cyclic disulfide 2-aryl-1,3-dithiolane 80. A large predominance of the tra .y-S-oxide 81 over the c/.v-dcri vati ve 82 is obtained for all the systems investigated (equation 46). However, the diastereoselectivity exhibited by V(V)/TBHP is remarkable315-325. 

A remarkably high diastereoselective excess was obtained in the addition of the anion of (S)-(-)-methyl 1-naphthyl sulfoxide to n-alkyl phenyl ketones. The sulfoxide was prepared in optically pure form by oxidation of the complex of methyl 1-naphthyl sulfide and 13-cyclodextrin with peracetic acid followed by crystallization. Desulfurization of the adducts provided enantiomerically pure tertiary alcohols (393]. 

Enantioselective oxidation of sulfides. m-Chloroperbenzoic acid attacks the sulfide 1 preferentially from the less hindered direction to introduce an oxygen atom with high diastereoselectivity.3... 

Asymmetric oxidation of sulfides to sulfoxides is undoubtedly the most straightforward route to optically pure (o.p.) sulfoxides. It is thus not surprising that various groups have been trying to develop efficient methods toward this end. Several o.p. sulfoxides have been obtained, by either diastereoselective or enantioselective oxidation of sulfides. 

Steric effects were responsible for the complete diastereocontrol observed in the oxidation of various 6-halopenicillins by dimethyl dioxirane (DMD). Only one of the two possible diastereomeric sulfoxides has been obtained in each case23 (Table 1). Scheme 3 shows that perborate oxidation of optically active sulfide 16 affords, with moderate diastereoselectivity (78% de), the (f )-sulfoxide 17,24 designed as chiral ligand for catalytic asymmetric synthesis. 

The main methodologies developed until now for enantioselective oxidation of sulfides are effective only in the oxidation of alkyl aryl sulfoxides. Dialkyl sulfoxides on the other hand are generally oxidized with only poor selectivity. In an attempt to solve this problem, Schenk s group69 recently reported a stereoselective oxidation of metal-coordinated thioethers with DMD. The prochiral thioether is first coordinated to a chiral ruthenium complex by reaction with the chloride complexes [CpRu[(S,S)-chiraphos]Cl], 36. Diastereoselective oxygen transfer from DMD produces the corresponding sulfoxides in high yield and selectivity. The chiral sulfoxides 37 are liberated from the complexes by treatment with sodium iodide. Several o.p. aryl methyl sulfoxides have been obtained by this method in moderate to high ee (Scheme 12). 

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