Sulfoxides as reagents

Under the correct conditions cyclopropanecarboxylic acids have been obtained by cleavage of various cyclopropyl ketones using ozone, potassium permanganate " and potassium hydroxide/dimethyl sulfoxide as reagents. Bromine under basic conditions was successful when the substrates were acetylcyclopropanes, but the yield varied from low to excellent. ... 

A great deal of effort has been expended in the development of ways to carry out the asymmetric oxidation of sultides to sulfoxides progress in this field has been exhaustively reviewed [114], This is interesting from th a theoretical viewpoint and from the utility of certain chiral sulfoxides as reagents in asymmetric synthesis [115]. Some natural products also contain sulfoxide stereogenic centers. 

Suitable strong bases include the sodium salt of dimethyl sulfoxide (in dimethyl sulfoxide as the solvent) and organolithium reagents (in diethyl ether or tetrahydrofuran). 

Besides simple alkyl-substituted sulfoxides, (a-chloroalkyl)sulfoxides have been used as reagents for diastereoselective addition reactions. Thus, a synthesis of enantiomerically pure 2-hydroxy carboxylates is based on the addition of (-)-l-[(l-chlorobutyl)sulfinyl]-4-methyl-benzene (10) to aldehydes433. The sulfoxide, optically pure with respect to the sulfoxide chirality but a mixture of diastereomers with respect to the a-sulfinyl carbon, can be readily deprotonated at — 55 °C. Subsequent addition to aldehydes afforded a mixture of the diastereomers 11A and 11B. Although the diastereoselectivity of the addition reaction is very low, the diastereomers are easily separated by flash chromatography. Thermal elimination of the sulfinyl group in refluxing xylene cleanly afforded the vinyl chlorides 12 A/12B in high chemical yield as a mixture of E- and Z-isomers. After ozonolysis in ethanol, followed by reductive workup, enantiomerically pure ethyl a-hydroxycarboxylates were obtained. 

Evans and Colombo35 are developing a different route to enantiomerically pure sulfoxides involving intermediate N-sulfinyl oxazolidinones 5. Reaction of these dia-stereomerically pure species with organometallic reagents gives enantiomerically pure sulfoxides, as illustrated by equation 5 carried out on a multigram scale. 

Methods for indirect oxidation have also been developed. The combination of KF/ wCPBA in acetonitrile and water has been used to generate KOF CH3CN reagent, a mild and selective oxidant that reacts at 0 °C with no overoxidation [78]. This reagent functions by providing a fluorosulfonium ion intermediate, which is hydrolyzed in the presence of water to the desired sulfoxides. As a result of the indirect oxidation method, the typical stereoselectivity of mCPBA-type oxidations is not observed here. The KOFCH3CN oxidant is similar in scope and mechanism to 1-fluoropyridinium triflates, Selectfluor [302] and the more classical t-butyl hypochlorite [288]. 

To arrive at racemic coriolin, Danishef sky and coworkers chose to add an acetonyl fragment to a bicyclic enedione by Diels-Alder chemistry (Scheme LXXIII) Treatment of the resulting adduct 695 sequentially with a series of conventional reagents produced the key intermediate 696. Suitable aldolization deUvered 697, the functionality in which was adjusted by deconjugation and reduction. Fiuther reduction of dPSiwith lithium in liquid ammonia and methanol followed by epoxidation afforded 699. Selective oxidation of the more accessible hydroxyl group and phenyl-sulfenylation gave 700 which experiences smooth elimination to 701 after conversion to the sulfoxide. As before, epoxidation completed the sequence. 

Oxidation of sulfides and sulfoxides, as discussed above, and alkylation of sulfinate salts are the most common methods used to obtain sulfones for synthetic purposes [71, 109-113], A hydrogen peroxide-urea-phthalic anhydride system was recently proposed as a mild convenient reagent for the efficient preparation of sulfones from organic sulfides [114]. 

Grignard reagent displaces menthol with inversion at sulfur (SN2) to give sulfoxide as a single enantiomer... 

In a sequence of steps, including a silyl Pnmmerer-rearrangement, Wemple et al. used chioromethyl phenyl sulfoxide as a phenyl thiocarbonyl-d reagent, as shown in Eq. (27) 30>. 

Recently Wright and co-workers have described a modified Gassman oxindole synthesis. They point out the problem associated with the preparation of the chlorosulfonium salt (reagent for Method 2) from chlorine gas and ethyl methylthioacetate, and demonstrated a modified procedure that makes use of a sulfoxide as a synthetic equivalent of a sulfenyl halide48 (Scheme 11). The Gassman procedure can also be applied to AZ-alkyl anilines43. 

Preparation. The reagent is prepared from (R)-(-l-)-methyl />-tolyl sulfoxide as shown. o o OH NaH... 

The use of anomeric sulfoxides as glycosylating reagents was reported by Kahne and coworkers in 1989 [51]. Upon activation with triflic anhydride at low temperatures, anomeric sulfoxides are transformed into extremely reactive glycosyl donors, which can glycosylate very hindered acceptors. The excellent reactivity of the sulfoxide donors coupled with the selectivity achieved by use of a participating group in the C2 position prompted their use in the synthesis of oligosaccharides on the solid support [52]. 

Dimethyl sulfoxide-derived reagent (a). Sodium methylsulfinylmethide, now generally known as Dimsylsodium, [ ch3s(o )=ch2 <—> CH3(s=0)-C H2]Na+ [1, 311, after line... 

The tosylate of trifluoroethanol furnishes by substitution and subsequent oxidation the terr-butylthioether and its sulfoxide as useful reagents for the attachment of trifluoroethylthioethers or their sulfoxides to multiple bonds according to the following scheme (Scheme 28, ref. 19). 

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