Sulfonium salts and sulfur ylides

Sulfonium salts are available by alkylation of sulfides. They have been known for a long time, and their syntheses and general reactivity have been reviewed [194-199]. 

In the context of this book we shall consider mainly the sulfonium salts as precursors of sulfonium ylides by deprotonation. Sulfur ylides can be viewed as zwitterionic species in which a carbanion is attached directly to a positively charged sulfur atom. 

Stabilized sulfur ylides have been obtained very early as dimethyl sulfonium fluorenylide [200]. 

However, their potentialities as synthetic intermediates were shown much later by the work of Corey and Chaykovsky [201, 202] on the preparations and methylene transfer reactions of dimethylsulfonium methylide (1) and dimethylsulfoxonium methylides (2). 

Reaction with carbonyl groups yields epoxides. 

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Previously, the same author [52] reported that compounds containing the tricoordinated sulfur cation, such as the triphenylsulfonium salt, worked as effective initiators in the free radical polymerization of MMA and styrene [52]. Because of the structural similarity of sulfonium salt and ylide, diphenyloxosulfonium bis-(me-thoxycarbonyl) methylide (POSY) (Scheme 28), which contains a tetracoordinated sulfur cation, was used as a photoinitiator by Kondo et al. [63] for the polymerization of MMA and styrene. The photopolymerization was carried out with a high-pressure mercury lamp the orders of reaction with respect to [POSY] and [MMA] were 0.5 and 1.0, respectively, as expected for radical polymerization. 

A single sulfonium ylide is beUeved to be formed as alkylation of oxathiane 3a gave the equatorial sulfonium salt exclusively [29]. Ylide conformation has been studied by X-ray, NMR, and computation [30]. All of these studies indicate that the preferred conformation of sulfur yUdes is one in which the filled orbital on the ylide carbon is orthogonal to the lone pair on sulfur. The barrier to rotation around the C-S bond of the semi-stabilized ylide, dimethylsulfonium fluorenide, has been found to be 42 1.0 kJmol [30]. This impHes that the ylide will adopt conformations 6a and 6b and that these will be in rapid equilibrium at room temperature. Of these two, conformation 6b will be favored as 6a suffers from... 

Sulfide 2a was later employed by Tang and coworkers in the reaction of 4-chlorobenzaldehyde with 3-trimethylsilylallyl bromide for the synthesis of viny-loxiranes. In the presence of 20mol% of 2a, the trans vinyl epoxide was obtained as the major diastereoisomer in 40% yield and 37% ee (21). Higher concentrations of both aldehyde and aUyhc bromide were found to be beneficial to the yields, because the high concentration of aUyhc bromide favors the formation of the sulfonium salt and the high concentration of aldehyde could probably allow capture of the sulfur ylide before the [2,3]-sigmatropic rearrangement (Scheme 20.6). This reaction with thiolane (THT) as a catalyst could also be carried out without solvent, but the yield was lower than that in t-BuOH. 

Sulfur ylides contain a carbanion, which is stabilizea oy an adjacent positively-charged sulfur. Ylides derived from alkylsulfonium salts are usually generated and utilized at low temperatures. Oxosulfonium ylides are, however, stable near room temperature. The most common method of ylide formation is deprotonation of a sulfonium salt. What has been said... 

Until this work, the reactions between the benzyl sulfonium ylide and ketones to give trisubstituted epoxides had not previously been used in asymmetric sulfur ylide-mediated epoxidation. It was found that good selectivities were obtained with cyclic ketones (Entry 6), but lower diastereo- and enantioselectivities resulted with acyclic ketones (Entries 7 and 8), which still remain challenging substrates for sulfur ylide-mediated epoxidation. In addition they showed that aryl-vinyl epoxides could also be synthesized with the aid of a,P-unsaturated sulfonium salts lOa-b (Scheme 1.4). 

The first attempt at a catalytic asymmetric sulfur ylide epoxidation was by Fur-ukawa s group [5]. The catalytic cycle was formed by initial alkylation of a sulfide (14), followed by deprotonation of the sulfonium salt 15 to form an ylide 16 and... 

There are four main factors that affect the enantioselectivity of sulfur ylide-mediated reactions i) the lone-pair selectivity of the sulfonium salt formation, ii) the conformation of the resulting ylide, iii) the face selectivity of the ylide, and iv) betaine reversibility. 

It is well known that aziridination with allylic ylides is difficult, due to the low reactivity of imines - relative to carbonyl compounds - towards ylide attack, although imines do react with highly reactive sulfur ylides such as Me2S+-CH2-. Dai and coworkers found aziridination with allylic ylides to be possible when the activated imines 22 were treated with allylic sulfonium salts 23 under phase-transfer conditions (Scheme 2.8) [15]. Although the stereoselectivities of the reaction were low, this was the first example of efficient preparation of vinylaziridines by an ylide route. Similar results were obtained with use of arsonium or telluronium salts [16]. The stereoselectivity of aziridination was improved by use of imines activated by a phosphinoyl group [17]. The same group also reported a catalytic sulfonium ylide-mediated aziridination to produce (2-phenylvinyl)aziridines, by treatment of arylsulfonylimines with cinnamyl bromide in the presence of solid K2C03 and catalytic dimethyl sulfide in MeCN [18]. Recently, the synthesis of 3-alkyl-2-vinyl-aziridines by extension of Dai s work was reported [19]. 

Metzner and co-workers reported a one-pot epoxidation reaction in which a chiral sulfide, an allyl halide, and an aromatic aldehyde were allowed to react to give a trons-vinylepoxide (Scheme 9.16c) [77]. This is an efficient approach, as the sulfonium salt is formed in situ and deprotonated to afford the corresponding ylide, and then reacts with the aldehyde. The sulfide was still required in stoichiometric amounts, however, as the catalytic process was too slow for synthetic purposes. The yields were good and the transxis ratios were high when Ri H, but the enantioselectivities were lower than with the sulfur ylides discussed above. 

Sulfur ylides have several applications as reagents in synthesis.282 Dimethylsul-fonium methylide and dimethylsulfoxonium methylide are particularly useful.283 These sulfur ylides are prepared by deprotonation of the corresponding sulfonium salts, both of which are commercially available. 

In addition the structure of the 1,2-azathiabenzene 78 was also confirmed by chemical evidence as shown in Scheme 10. Protonation of 78a (R1 = R2 = Me) with 70% perchloric acid yielded the corresponding cyclic amino sulfonium salt 82a in 87% yield, but not the starting sulfonium compound 76a, suggesting predominance of sulfilimine structure 78a rather than cyclic sulfonium ylide stmcture 80a. Thus, compound 78 could be recognized as the first example of a 1,2-azathiabenzene having sulfur at a bridgehead position. A proposed mechanism for the formation of 78 and 79 is shown in Scheme 9. The most acidic proton adjacent to sulfur in 76 is deprotonated with... 

Sulfur ylides are a classic reagent for the conversion of carbonyl compounds to epoxides. Chiral camphor-derived sulfur ylides have been used in the enantioselective synthesis of epoxy-amides <06JA2105>. Reaction of sulfonium salt 12 with an aldehyde and base provides the epoxide 13 in generally excellent yields. While the yield of the reaction was quite good across a variety of R groups, the enantioselectivity was variable. For example benzaldehyde provides 13 (R = Ph) in 97% ee while isobutyraldehyde provides 13 (R = i-Pr) with only 10% ee. These epoxy amides could be converted to a number of epoxide-opened... 

An analogous study has been carried out on ylide formation in cyclic sulfonium salts. Using the conformationally rigid systems in Table 12, relative kinetic acidities for Ho and Heq were determined. The results show that it is possible to remove one proton selectively, and thereby transfer chirality at sulfur to the neighbouring carbon atom (78JA200). As rigidity increases the differential kinetic acidity also increases but this is due not to an increase in overall acidity, rather to a decrease in lability of the axial proton in these... 

These reactions rapidly found wide use and success, and many other sulfur ylides have been prepared and exploited [194, 195, 203, 204]. Various experimental procedures are to be found in the detailed monograph by Trost and Melvin [204] for sulfonium salts, ylides, epoxidations and cyclopropanations. 

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]. 

It should be mentioned at this stage that in addition to the catalytic version, numerous sulfur-ylide mediated asymmetric diastereoselec-tive epoxidations which require the use of stoichiometric amounts of the sulfur-ylide were reported. In these cases, the sulfonium salts had to be prepared in a first step, and were used in a subsequent diastereoselective epoxidation step. For some selected references for this type of stoichiometric asymmetric two-step epoxidation, see (a) T. Durst, L. Breau, R. N. 

Finally, Sato and co-workers have added a twist to the known preparation of epoxides from the action of sulfur ylides on carbonyl compounds. In this version, the requisite sulfur ylides are formed by desilylation of [(trimethylsilyl)methyI]sulfonium salts (e.g., 45) in DMSO. This avoids the strongly basic conditions typically encountered in the preparation of sulfur ylides [95SYN649],... 

Recently, Tang, Wu and co-workers have reported the synthesis of vinylcyclopro-panes using an alternative catalytic cycle for sulfur ylide-catalyzed cyclopropanation (see Scheme 10.22) [98]. Sulfonium salt 41a or 41b was deprotonated by CS2CO3 to form an ylide which then reacted with chalcones 37 to form cyclopropanes and a sulfide. The sulfonium salt was regenerated in situ through reaction... 

The reaction requires the addition of base (conunonly triethylamine) and results in the formation of an ylide (2 Scheme 3), which collapses intramolecularly to the carbonyl compound. - Further siqiportive evidence for ylide formation lies in the observation that sulfonium salts lacking a hydrogen a to the sulfur do not break down to form the carbonyl compound." ... 

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