Use of sulfur ylides

The comparison between the reactions of a carbonyl compound with a phosphorus ylide (Wittig s reagent) on one hand and a sulfur ylide on the other shows dearly the complementarity of these reagents in the strategy of synthesis. 

Both reagents transfer a methylene group in efficient and selective pathways. So it is not surprising that sulfur ylides have been widely used as synthetic tools for the preparation of epoxides. The reactions can make use of sulfonium salts under phase transfer catalytic conditions, and the cheap and easily accessible trimethyl sulfonium methyl sulfate and triethylsulfonium ethyl sulfate were found to show a high reactivity under such conditions [450]. 

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Recently, in connection with the use of sulfur ylides in polymerization, Kondo and his coworkers [64] attempted to use diphenylsulfonium bis(methoxycarbo-nyl)methylide (DPSY) (Schemes 27, 29) methylphen-ylsulfonium bis-(methoxycarbonyl)methylide (MPSY) (Scheme 30) and dimethylsulfonium bis (methoxycar-bonyl) methylide (DMSY) (Scheme 31) as photoinitiators for the polymerization of MMA and styrene. They concluded that DPSY and MPSY are effective photoini-... 

There is also another approach to the use of sulfur ylides in the synthesis of cyclic nitronates (5) (see Eq. 2 Ref. 61). Salts (14) as Michael substrates add... 

The use of sulfur ylides has been covered by thorough reviews133 to which the reader is referred for extensive listings of examples. A few representative cases are given in Table 8. 

For reviews on the use of sulfur-ylides for the synthesis of epoxides, see (a) B. M. Trost, L. S. Melvon, Sulfur Ylides, Academic Press, New York, 1975 (b) J. Aube in Comprehensive Organic Synthesis (Eds. B. M. Trost,... 

The use of sulfur ylides as versatile reactants in these domino reactions was also reported by Briere and co-workers [53]. They developed a highly diastereoselective synthesis of spiro epoxyoxindoles from reaction between in s/Yw-generated sulfur ylides and isatin derivatives. Moderate enantioselectivity (30% ee) could be achieved with a C2-symmetrical chiral sulfur ylide. 

Saijo R, Kawase M (2012) The use of sulfur ylides in the synthesis of 3-tilkyl(aryl)thio-4-trifluoromethylpyrroles from mesoionic 4-trilluoroacetyl-l,3-oxazolium-5-olates. Tetrahedron Lett 53 2782-2785... 

Very similar results have also been reported with the use of sulfur ylides as donor molecules [179]. With regard to the asymmetric Biginelli reaction [180] and mulhcomponent coupling reachons [181] using 30 or its analog as a catalyst, only references are given here. 

The intramolecular addition of sulfur ylides to imines (e.g. 72) has proven to be an excellent route to fused-ring aziridines (e.g. 73) <06AG(I)7066>. The addition of a sulfonamide to a vinylsulfonium salt leads to the formation of the sulfur ylide 72. The ylide then undergoes an intramolecular addition to form the product fused-ring aziridine 73. This method has also been used for the synthesis of fused-ring epoxides. 

In all the above examples, the synthesis of nitronates (5) is rather chemose-lective. In any case, data on the formation of their structural isomers, viz, the corresponding nitrocyclopropanes (13), are lacking. However, the synthesis of five-membered nitronates (5) with the use of sulfur or selenium ylides is not chemoselective (see Scheme 3.16). 

The source of the latter from the appropriate ketone 194 using cyclopropyl sulfur ylide chemistry is apparent. The ultimate starting material is the well known diketone 195 which is easily available in optically active form. 

Sulfur ylides are among the most interesting carbon nucleophiles and their synthetic importance has been recently reviewed.One especially interesting use of these ylides is their application to the synthesis of cyclopropane derivatives using unsaturated oxazolones. For example, stabilized sulfur yhdes react with unsaturated oxazolones 629 via a Michael reaction to give oxazolone spirocyclopropanes 630 as shown in Scheme 7.202 and Table 7.46 (Fig. 7.57), whereas the less stabilized sulfur ylides give ring-opened products 631 as the major compounds (Scheme 7.202). ... 

The enantiomeric synthesis of rranj-3,4-disubstituted tetrahydrothiophenes using a sulfur ylide cycloaddition has been reported <990L1667>. The sulfur ylide derived from the action of cesium fluoride on sulfide 111 underwent an asymmetric cycloaddition with chiral a,p-unsaturated camphorsultam amide 112 giving tetrahydrothiophene 113 (80% de). The configuration was confirmed by cleavage of the chiral auxiliary followed by reductive desulfurization with Raney-Ni which gave known carboxylic acid 114. 

Some organic reactions can be accomplished by using two-layer systems in which phase-transfer catalysts play an important role (34). The phase-transfer reaction proceeds via ion pairs, and asymmetric induction is expected to emerge when chiral quaternary ammonium salts are used. The ion-pair interaction, however, is usually not strong enough to control the absolute stereochemistry of the reaction (35). Numerous trials have resulted in low or only moderate stereoselectivity, probably because of the loose orientation of the ion-paired intermediates or transition states. These reactions include, but are not limited to, carbene addition to alkenes, reaction of sulfur ylides and aldehydes, nucleophilic substitution of secondary alkyl halides, Darzens reaction, chlorination... 

Boekelheide and his collaborators [407] have described a two-step sequence for transforming sulfide linkages to carbon-carbon double bonds — Stevens rearrangement of sulfur ylides and Hofmann elimination — which they found particularly useful for the synthesis of cyclophane derivatives, such as the [2.2]metaparacyclophane-l,9-diene shown. The Ramberg-Backlund rearrangement (see Section 4.3.2) was unsatisfactory for such highly strained molecules. 

Ylides based upon sulfur are the most generally useful in these cyclopropane-forming reactions.133 Early work in this area was done with the simple dimethyloxysulfonium methylide (9) derived from dimethyl sulfoxide. The even simpler dimethylsulfonium methylide (10) was studied at the same time as a reagent primarily for the conversion of carbonyl compounds into epoxides.134 Somewhat later, other types of sulfur ylides were developed, among which the nitrogen-substituted derivatives such as (11) are... 

The reactions are normally limited to the use of electron deficient alkenes as substrates. However, there have been some reports of copper-catalyzed reactions of sulfur ylides with simple alkenes, as exemplified in equation (16).147... 

Ylides of other elements have been used much less commonly than sulfur ylides in cyclopropanations. Rather, other ylides are better known for their uses in other types of reactions, the best example being the use of phosphonium ylides in the Wittig reaction with carbonyl compounds to give alkenes. Nonetheless, some cases of cyclopropanations have been reported with phosphonium ylides and the related arsenic derivatives. Examples are given in Table 9. 

The use of stoichiometric amounts of sulfur ylides in the diastereoselective addition to imines has been recognized for a long time as a means of efficient synthesis... 

As shown above (see also Scheme 6.87B), formation of sulfur ylides by reaction of a carbenoid with a sulfide is an efficient alternative which has also been found to be applicable to enolizable and base-sensitive aldehydes. This route, developed by the Aggarwal group, is based on use of a metal catalyst to form a carbene which subsequently reacts with the sulfide generating the sulfur ylide [200, 212, 213, 226]. Because the catalytically active species of the asymmetric process is the sulfide, this concept can be also regarded as an organocatalytic reaction. 

In this chapter, we will review the use of ylides as enantioselective organocata-lysts. Three main types of asymmetric reaction have been achieved using ylides as catalysts, namely epoxidation, aziridination, and cyclopropanation. Each of these will be dealt with in turn. The use of an ylide to achieve these transformations involves the construction of a C-C bond, a three-membered ring, and two new adjacent stereocenters with control of absolute and relative stereochemistry in one step. These are potentially very efficient transformations in the synthetic chemist s arsenal, but they are also challenging ones to control, as we shall see. Sulfur ylides dominate in these types of transformations because they show the best combination of ylide stability [1] with leaving group ability [2] of the onium ion in the intermediate betaine. In addition, the use of nitrogen, selenium and tellurium ylides as catalysts will also be described. 

A variation of the [C + C=N] pathway involves the addition of sulfur ylides to imines and this method has been effectively used to access a wide range of substituted aziridines under mild reaction conditions. Although high enantiomeric excesses can be achieved by using a chiral sulfur ylide (up to 98%), the m//rstepwise mechanism via a betaine intermediate . Sulfur ylides can be conveniently generated in situ from alkyl halides and chiral sulfides thus, benzyl bromide and tosyl imine in the presence of a camphor-derived chiral sulfide mediator provide aziridine 4 in practically quantitative yield as a 3 1 mixture of /Z-isomers and in 92% ee (A-isomer) (Scheme 8) <2001TL5451>. 

However, the generation of only single isomer was achieved by using a shape-selective catalyst. The Cu(I) catalysts coordinated to chiral ligand, 3.47, 3.48 or 3.49, are used in the selective synthesis of sulfur ylides. 

Titanosilicate catalysis has been examined by DFT studies <2001PCB3493>. The reaction of vinylcarbenoids and aromatic aldehydes has also been studied <2001JOC5395>. A DFT study of a model system for epoxide formation using a sulfur ylide has been published by Aggarwal et al. <2002JA5747>. 

The reaction of sulfur ylides e.g. Me2S -CH2) with carbonyl compounds is a useful route to epoxides. 

The use of sulfur in place of the phosphorus brings about a different mode of decomposition of the intermediate betaine. Two sulfur ylides, dimethylsulfonium methylide (Scheme 3.49a) and dimethylsulfoxonium methylide (Scheme 3.49b), have been used. Both ylides react with ketones to give epoxides, but the stereochemistry may differ. 

Deprotonadon of thioanisole and addition of a carbonyl compound affords an isolable hydroxy sulfide which can then be alkylated (Scheme 7). Treatment with base generates the same betaine that would have been formed using the sulfur ylide approach, and effects the intramolecular displacement reaction. The addition of methylthiomethyllithium to 2-cyclohexenone exclusively provides the 1,2-addition prod-uct the dianions derived from phenylmethanethiol or allylthiol react in a similar manner. In one case a 6-keto steroidal substrate was found to undergo smooth methylenation using this procedure. 

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