Preparation of Sulfoxides and Sulfones

Thioglycosides have been prepared on solid phase by glycosylation of thiols with various types of glycosyl donor. Carbohydrate-derived thioethers have been used either to link carbohydrates to thiol-functionalized supports [9,26,78,79] or as glycosyl donors for the preparation of glycosides on solid phase (see Section 16.3.3). 

Sulfoxides and sulfones can be prepared on cross-linked polystyrene by oxidation of thioethers. The most commonly used reagent for this purpose is MCPBA in DCM [8,12,32,57,80-82] or dioxane [50,83] (Table 8.6), but other oxidants such as H2O2 in acetic acid [34], oxone (Entry 7, Table 8.6), or oxaziridines [84] have also been used. PEG-bound thioethers have been converted into sulfones by oxidation with MCPBA in DCM [52,54] or with Os04/NMO [85], The oxidation of thioethers to sulfoxides requires careful control of the reaction conditions to prevent the formation of sulfones. Sulfones have also been prepared by S-alkylation of polystyrene-bound sulfi-nates (Entries 8 and 9, Table 8.6), by a-alkylation of sulfones (BuLi, THF, alkyl halide [86]), and by addition of sulfinyl radicals to resin-bound alkenes or alkynes (Entry 11, Table 8.6). 

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Pees B., Sindt M., Paul J.M. Mieloszynski J.L. (2002). Synthese et caracteiisation physico-chimiques de polyaaylates d (0-p>erfluorooctyl-atkyle effet p ir- impair. Eur. Polym. Jour, vol.38, n°5, p>p. 921-931 (May 2002), ISSN 0014-3057 Pees B., Paul J.M., Oget N, Sindt M., Mieloszynski J.L. (2003). Synthesis of fluoro-substituted monomers bearing a functionalised lateral chain. Part 2 Preparation of sulfoxides and sulfones containing monomers, J. Fluor.Chem., voLl24, n°2, pp.l39-146 (December 2003) ISSN 0022-1139... 

Polymeric percarboxylic acids (33) have been prepared from PS analogues of benzoic acid and benzoyl chloride as in equation (13). Expoxides are formed from di- and tri-substituted alkenes with (33) at 40 °C. The PS-peracids also oxidized sulfides to mixtures of sulfoxide and sulfone, and with penicillins and deacetoxycephalosporins gave sulfoxides in high yield. 

Heteroaromatic sulfur compounds do form sulfoxides and sulfones, but these derivatives have their own special reactivity. Francesca Clerici (Milan, Italy) has now provided an up-to-date survey of the preparation and properties of the S-oxides of thiazoles and thiadiazoles, collecting literature scattered in many publications. 

Oxidation of 7-hydroxy- and 7-aryl-5-oxo-2,3-dihydro-5//-pyrido[l,2,3- f< ]-l,4-benzothiazine-6-carboxylates and 6-carboxamides with 3-chloroper-oxybenzoic acid in CH2CI2 yielded sulfoxides and sulfones, depending on the molar ratio of the substrate and oxidizing agent (00MIP7). A sulfoxide was prepared by the oxidation of ethyl (3S)-3-methyl-10-(2,6-dimethyl-4-pyridyl)-7-oxo-2,3-dihydro-7//-pyrido[l,2,3-<7c]-l,4-benzothiazine-6-carbox-ylate (OOMIPIO). 

Oxidation of thiirane and thiirene oxides to the dioxides is the best method to obtain the sulfones. Indeed, in the acyclic, or large-ring systems, the sequence sulfide- sulfoxide - sulfone is by far the easiest method to prepare sulfoxides and sulfones. The situation is different in the three-membered ring series Thus, oxidation of thiiranes to the oxides by either perbenzoic acid or m-chloroperbenzoic acid under mild conditions affords the corresponding thiirane sulfoxides in almost quantitative yield - . However, further... 

J. R. McCarthy, D. P. Matthews, and J. P. Paolini 209 REACTION OF SULFOXIDES WITH DIETHYLAMINOSULFUR TRIFLUORIDE PREPARATION OF FLUOROMETHYL PHENYL SULFONE, A REAGENT FOR THE SYNTHESIS OF FLUOROALKENES... 

The oxidation of sulfides to sulfoxides (1 eq. of oxidant) and sulfones (2 eq. of oxidant) is possible in the absence of a catalyst by employing the perhydrate prepared from hexafluoroacetone or 2-hydroperoxy-l,l,l-trifluoropropan-2-ol as reported by Ganeshpure and Adam (Scheme 99 f°. The reaction is highly chemoselective and sulfoxidation occurs in the presence of double bonds and amine functions, which were not oxidized. With one equivalent of the a-hydroxyhydroperoxide, diphenyl sulfide was selectively transformed to the sulfoxide in quantitative yield and with two equivalents of oxidant the corresponding sulfone was quantitatively obtained. 2-Hydroperoxy-l,l,l-fluoropropan-2-ol as an electrophilic oxidant oxidizes thianthrene-5-oxide almost exclusively to the corresponding cw-disulfoxide, although low conversions were observed (15%) (Scheme 99). Deprotonation of this oxidant with sodium carbonate in methanol leads to a peroxo anion, which is a nucleophilic oxidant and oxidizes thianthrene-5-oxide preferentially to the sulfone. 

In summary, the direct insertion of zinc dust to organic halides is an excellent method for preparing a broad range of polyfunctional organozinc halides bearing various functional groups like an ester" , an ether, an acetate" , a ketone, cyano", halide" , N,N-bis(trimethylsilyl)amino °, primary and secondary amino, amide, phthalimide , sulfide, sulfoxide and sulfone , boronic ester , enone " or a phosphonate . An alternative method is based on transmetalation reactions. 

Due to the good nucleophilic nature of sulfur, formation of new C—S bonds is relatively easy. This property has been used for intramolecular peptide cyclization 1 and was exploited for preparation of methylenethio ether surrogates, t >[CH2—S], initially as peptide gap inhibitors for blocking collagenase action. 2 These surrogates were later converted into sulfoxide and sulfone derivatives. This expansion of amide replacements compelled a more generalized nomenclature system for pseudopeptides (amides with one or more amide bond surrogates) and led directly to the psi-bracket convention. 1 ... 

Sulfoxide and sulfone derivatives are best prepared by oxidation of a sulfide precursor, though specific 2-substitution may be achieved via metallation of the oxidized system, as outlined in Section 2.25.3.1. 

Oxidation of the saturated heterocycle to sulfoxide and sulfone derivatives affords solvents for the preparation of polyacrylonitrile (62BEP613056), or corrosion inhibitors (e.g. 147)... 

Even the comparatively unreactive phenoxazine and phenothiazine systems undergo halogenation and nitration with ease and it is normal to prepare monosubstituted derivatives by stepwise procedures rather than by direct electrophilic attack. Indeed, the nitration of phenoxazine is uncontrollable and even N-acylphenoxazines afford a mixture of di- and tetra-nitro products (03CB475). Similarly phenothiazine and nitric acid produce a complex mixture of nitrated sulfoxides and sulfones. Chlorine in DMSO at 40 °C reacts with phenothiazine to yield 3,7-dichlorophenothiazine, whereas cupric chloride gives the 1,7-isomer (76JPR353). Direct bromination of phenoxazine produces a mixture of 3-bromo- and 3,7-dibromo-phenoxazines, while thionyl chloride affords the 1,3,7,9-tetrachloro derivative (60ZOB1893). 

Sulfoxides and sulfones of the monocyclic and polycyclic thiazines are not normally made by direct oxidation, but rather from substrates already at the correct oxidation level. 1-Oxides (254), for example, are prepared either by the addition of dimethylsulfoxonium methylide to cyanides (65CB3724) or to cyanamides (Scheme 114) (76H(4)1875). 

Prakash, G. K. S. Hu, J. Olah, G. A. Preparation of tri- and difluoromethylsilanes via an unusual magnesium metal-mediated reductive tri- and difluoromethylation of chlorosilanes using tri- and difluoromethyl sulfides, sulfoxides, and sulfones. J. Org. Chem. 2003, 68, 4457-4463. 

Electrophilic additions to vinyl sulfoxides and sulfones allow for further functionalization of these compounds at the a-position. Deprotonation of the a-hydrogen, under appropriate conditions, gives rise to a-vinyl anions which can be trapped by electrophiles. This protocol has been employed in the synthesis of a diverse range of compounds, such as 34 and 37, 40 and 43, and 46 (see Schemes 9, 10, and 11, respectively). Both enantiomers of optically pure propargylic alcohols (115) were conveniently prepared by the reaction of the a-vinyl anion of 2-(trimethylsilyl) vinyl... 

Organic hydroperoxides are generally used for the preparation of sulfoxides from sulfides, - while sulfones can be obtained in neutral organic solvents in the presence of metal catalysts such as V, Mo and Ti oxides at 50-70 C. Two polymer-supported reagents which involve peroxy acid groups and bound hypervalent vanadium(V) and molybdenum(VI) compounds have been developed for facile oxidation of sulfoxides to sulfones. 

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