Alkyl sulfides, oxidation

Nucleophilic reactivity of exocyclic sulfur appears in acidic medium. 2-AryI thiazolyl sulfones are obtained from the corresponding sulfides by oxidation with HjO- in HOAc at 100°C (272). The same oxidation takes place with alkyl sulfides (203. 214, 273-275) and dithiazolylsulfides (129). However, the same reaction with 2-benzylthio derivatives gives benzylal-cohol and the related A-4-thiazoline-2-thione (169). 

Usually, organoboranes are sensitive to oxygen. Simple trialkylboranes are spontaneously flammable in contact with air. Nevertheless, under carefully controlled conditions the reaction of organoboranes with oxygen can be used for the preparation of alcohols or alkyl hydroperoxides (228,229). Aldehydes are produced by oxidation of primary alkylboranes with pyridinium chi orochrom ate (188). Chromic acid at pH < 3 transforms secondary alkyl and cycloalkylboranes into ketones pyridinium chi orochrom ate can also be used (230,231). A convenient procedure for the direct conversion of terminal alkenes into carboxyUc acids employs hydroboration with dibromoborane—dimethyl sulfide and oxidation of the intermediate alkyldibromoborane with chromium trioxide in 90% aqueous acetic acid (232,233). 

The kinetics of formation and hydrolysis of /-C H OCl have been investigated (262). The chemistry of alkyl hypochlorites, /-C H OCl in particular, has been extensively explored (247). /-Butyl hypochlorite reacts with a variety of olefins via a photoinduced radical chain process to give good yields of aUyflc chlorides (263). Steroid alcohols can be oxidized and chlorinated with /-C H OCl to give good yields of ketosteroids and chlorosteroids (264) (see Steroids). /-Butyl hypochlorite is a more satisfactory reagent than HOCl for /V-chlorination of amines (265). Sulfides are oxidized in excellent yields to sulfoxides without concomitant formation of sulfones (266). 2-Amino-1, 4-quinones are rapidly chlorinated at room temperature chlorination occurs specifically at the position adjacent to the amino group (267). Anhydropenicillin is converted almost quantitatively to its 6-methoxy derivative by /-C H OCl in methanol (268). Reaction of unsaturated hydroperoxides with /-C H OCl provides monocyclic and bicycHc chloroalkyl 1,2-dioxolanes. 

As already mentioned above, sulfides are oxidized to the corresponding sulfoxides with alkyl hydroperoxides in the presence of various metal catalysts like Mo, W, Ti and V. In the presence of excess hydroperoxide further oxidation to the sulfone occurs. Sulfides are generally oxidized much faster than alkenes, which is reflected in the selective oxidation of unsaturated sulfides exclusively at the sulfur atom. During the last years many asymmetric versions of this reaction have been developed and can be mainly divided... 

In combination with H2O2 (salen)Mn(III) complexes 173a, b, i-n have also been employed by Jacobsen and coworkers as catalysts for the asymmetric oxidation of sulfides to sulfoxides, without a need for additives. From the structurally and electronically different Mn-salen catalysts screened, 173i turned out to be the most active and selective one (equation 58) . While dialkyl sulfides underwenf uncafalyzed oxidation with H2O2, aryl alkyl sulfides were oxidized only slowly compared wifh fhe cafalyzed pathway. Using... 

Various alkyl aryl and diaryl sulfides were oxidized selectively to the corresponding sulfoxides in high yields as the major products using sulfonylperoxy intermediate 51 (equation 86) ". ... 

Organometallic compounds asymmetric catalysis, 11, 255 chiral auxiliaries, 266 enantioselectivity, 255 see also specific compounds Organozinc chemistry, 260 amino alcohols, 261, 355 chirality amplification, 273 efficiency origins, 273 ligand acceleration, 260 molecular structures, 276 reaction mechanism, 269 transition state models, 264 turnover-limiting step, 271 Orthohydroxylation, naphthol, 230 Osmium, olefin dihydroxylation, 150 Oxametallacycle intermediates, 150, 152 Oxazaborolidines, 134 Oxazoline, 356 Oxidation amines, 155 olefins, 137, 150 reduction, 5 sulfides, 155 Oxidative addition, 5 amine isomerization, 111 hydrogen molecule, 16 Oxidative dimerization, chiral phenols, 287 Oximes, borane reduction, 135 Oxindole alkylation, 338 Oxiranes, enantioselective synthesis, 137, 289, 326, 333, 349, 361 Oxonium polymerization, 332 Oxo process, 162 Oxovanadium complexes, 220 Oxygenation, C—H bonds, 149... 

Complexity is added to the study of this system by the ready functionalization of the sulfur atom by alkylation, oxidation and imination. 5-Alkylation to produce a compound such as (9) <76T1873) affords a system in which either of two possible chair conformers possesses an axial t-butyl group, and this system therefore exists preferentially in a twist conformation (10). Where no such conflicts occur the sulfur substituent adopts the equatorial position in a chair form. Inversion of configuration at sulfur in cyclic sulfides has been investigated in the system (11) (12) and the corresponding ylides (13) (14) (77JA2337). 

There is one report in which sulfides are oxidized by PDC in aqueous acetic acid however normally the oxidation of alcohols is quicker, so that selective oxidation of alcohols with PDC is possible in the presence of sulfur containing compounds, such as thiophenes,153 aryl sulfides,154 alkyl sulfides155 and dithioacetals.156... 

Pinhey utilized the decarboxylative rearrangement of 2 to the nor-alkyl pyridyl sulfide 3, oxidation to the corresponding sulfoxide and thermal elimination sequence in a simple transformation of podocarpic acid 4 into useful synthons 5 (for example, in vitamin D3 synthesis) for steroid CD-ring systems, as shown in Scheme l.8... 

We can illustrate the synthesis of allylic alcohols from allylic sulfoxides with this synthesis of the natural product nuciferal. We mentioned this route on p. 1257 because it makes use of a heterocyclic allyl sulfide to introduce an alkyl substituent regioselectively. The allyl sulfide is oxidized to the sulfoxide, which is converted to the rearranged allylic alcohol with diethylamine as the thiophile. Nuciferal is obtained by oxidizing the allylic alcohol to an aldehyde with manganese dioxide. 

Chiral sulfoxides. The Sharpless reagent lor asymmetric epoxidation also effects asymmetric oxidation of prochiral sulfides to sulfoxides. The most satisfactory results are obtained for the stoichiometry Ti(0-(-Pr)4/L DET/H20/(CH,),C00H = 1 2 1 2 for I equiv. of sulfide. In the series of alkyl p-tolyl sulfides, the (R)-sulfoxide is obtained in 41-90% ee the enantioselectivity is highest when the alkyl group is methyl. Methyl phenyl sulfide is oxidized to the (R)-sulfoxide in 81% ee. Even optically active dialkyl sulfoxides can be prepared in 50-71% ee the enantioselectivity is highest for methyl octyl sulfoxide. 

The typical S-oxidation with BVMOs allows the formation of chiral sulfoxides from organic sulfides. This oxidation has received much interest in organic chemistry due to its use in the synthesis of enantiomerically enriched materials as chiral auxiliaries or directly as biologically active ingredients. This reaction has been studied extensively with CHMO from Adnetohacter showing high enantioselectivi-ties in the sulfoxidation of alkyl aryl sulfides, disulfides, dialkyl sulfides, and cychc and acyclic 1,3-dithioacetals [90]. CHMO also catalyzes the enantioselective oxida-hon of organic cyclic sulfites to sulfates [91]. 

The present procedure is based on the use of fluoroalkyl alcohols as solvents in oxidation reactions. The method is efficient and versatile, and produces disulfides and sulfoxides under mild conditions. These reactions have also been developed using hexafluoroisopropyl alcohol (HFIP) as solvent with a large variety of substrates (alkyl sulfides, alkyl thiols, vinyl sulfides, fiuorinated vinyl sulfides, thioglucosides) by Begue et al."> Replacement of HFIP with trifluoroethanol, a more common and less expensive solvent, also allows the use of mild conditions and affords high yields of disulfides and sulfoxides without contamination. 30% Aqueous hydrogen peroxide is inexpensive and, since water is the sole byproduct, this method is environmentally friendly. 

Dialkyl sulfides, alkyl aryl sulfides, diaryl sulfides, and cyclic sulfides are oxidized to the corresponding sulfoxides or sulfones. Often, both products can be obtained on oxidation with the same oxidant, depending on... 

Alkyl aryl sulfides electrochemically oxidized on electrodes whose surfaces were modified by coating them with optically active compounds like camphoric acid [89] and poly(amino acids) [90, 91] afford mixtures of sulfoxides with variable enantiomeric excess. An optical yield of 93% is claimed when f-butyl phenyl sulfide is oxidized at a Pt electrode doubly coated with polypyrrole and poly(L-valine) [91]. 

A large number of alkyl aryl sulfides were oxidized electrochemically under superdry conditions using MeCN as solvent and BU4NBF4 or LiC104 as supporting electrolytes for cyclic voltammetry and preparative electrolyses, respectively [97]. 

Alkyl aryl sulfides, when oxidized in HOAc-Ac20-NaOAc, produce the corresponding sulfoxides and the a-acetoxy derivatives [102]. The formation of the latter compounds was ascribed to a Pummerer rearrangement of the initially formed sulfoxide. These compounds normally are obtained by heating sulfoxides with Ac O at elevated temperature, and it seemed attractive to perform the electrolyses in the boiling solvent to form the a-acetyoxy derivatives as the sole product. This approach was shown to be adequate, and yields are given in Eq. (54) [102]. 

Miscellaneous reactions. The sulfides are oxidized by an excess of e.g. hydrogen peroxide or 3-chloroperoxybenzolc acid to the corresponding sulfones. A controlled addition of peroxide yields a mixture of sulfoxide and sulfone products. The use of nitronium hexafluorophosphate or tetrafluoroborate to oxidize dlalkyl, aryl alkyl or dlaryl sulfides yields only the corresponding sulfoxide under extremely mild conditions (224). Sulfoxides may be further oxidized to the corresponding sulfones In good yield by the nitronium salts as well (225). 

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