Sulfonium salts deprotonation

Catalytic Cycle Based on Sulfide Alkylation and Sulfonium Salt Deprotonation... 

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... 

Two efficient syntheses of strained cyclophanes indicate the synthetic potential of allyl or benzyl sulfide intermediates, in which the combined nucleophilicity and redox activity of the sulfur atom can be used. The dibenzylic sulfides from xylylene dihalides and -dithiols can be methylated with dimethoxycarbenium tetrafiuoroborate (H. Meerwein, 1960 R.F. Borch, 1968, 1969 from trimethyl orthoformate and BFj, 3 4). The sulfonium salts are deprotonated and rearrange to methyl sulfides (Stevens rearrangement). Repeated methylation and Hofmann elimination yields double bonds (R.H. Mitchell, 1974). 

Upon addition of a base—triethylamine is often used—the sulfonium salt 7 is deprotonated to give a sulfonium ylide 8. The latter decomposes into the carbonyl compound 2 and dimethyl sulfide 9 through /3-elimination via a cyclic transition state. 

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... 

Chiral sulfonium salts derived from oxathianes have been developed for stoichiometric epoxidation reactions. The sulfonium salts were deprotonated and allowed to react with a, 3-unsaturated aldehydes to give trons-vinylepoxides with excellent ees and transxis ratios (Scheme 9.16b) [76]. The yields were generally high [75], and the best results were obtained with Ar = 4-OMePh. 

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. 

Thia-[2,3]-Wittig sigmatropic rearrangement of lithiated carbanions 47, obtained by deprotonation of the S-allylic sulfides 46, affords the thiols 48 or their alkylated derivatives 49. The corresponding sulfonium ylides 51, prepared by deprotonation of the sulfonium salts 50 also undergoes a [2,3]-sigmatropic shift leading to the same sulfides 49 [36,38] (Scheme 13). As far as stereochemistry is concerned, with crotyl (R R =H,R =Me) and cinnamyl (R, R =H,R =Ph) derivatives, it has been shown that the diastereoselectivity depends on the nature of the R substituent and on the use of a carbanion or an ylide as intermediate. 

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. 

Allylic sulfonium ylides readily undergo [2,3]-sigmatropic rearrangement.280 The ylides are usually formed by deprotonation of the S-allyl sulfonium salts. 

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... 

Related to the sulfonium salts and their ylides are the oxosulfonium salts and their ylides. Cyclopropyl (dimethylamino)phenyloxosulfonium fluoroborate 11, available by routes analogous to the preparation of 9, suffers smooth deprotonation to the corresponding ylide upon treatment with base (Eq. 26) 28. ... 

Rapid deprotonation of the dicationic complex yielding the final product, sulfonium salt, that is, (HetH- ArH)2+ (HetH-Ar)+... 

Chiral bis-lithium amide bases have been used for enantiotopic deprotonation of the sulfonium salt of 1,4-oxathiane 86. The anion undergoes an enantioselective thia-Sommelet rearrangement to afford the 3-substituted-1,4-oxathiane 87. Only bis-lithium amide bases were effective, giving products with high diastereoselectivity and with low to moderate enantioselectivity (Equation 13) <2003TL8203>. 

Sulfonium ylides generated through base-promoted deprotonation of sulfonium salt have been extensively studied. The reaction of sulfides with a diazo carbonyl compound in the presence of a transition metal catalyst is an alternative approach to obtain sulfonium ylides. Sulfonium ylides are more stable than the corresponding oxonium ylides. Stable sulfonium ylides generated by the reaction of an Rh(ii) carbene complex with thiophene have been reported (Figure 5). ... 

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. 

The simplest sulfur ylids are formed from sulfonium salts 69 by deprotonation in base. These ylids react with carbonyl compounds to give epoxides.18 Nucleophilic attack on the carbonyl group 70 is followed by elimination 71 of dimethylsulfide 72 and formation of the epoxide 73. You should compare diagram 71 with diagram 23 in chapter 15. The phosphonium ylid reacted by formation of a P-0 bond and an alkene in the Wittig reaction. The sulfonium compound reacts by formation of a C-O bond 71 as the S-O bond is much weaker than the P-0 bond. The sulfonium salt 69 can be reformed by reaction of 72 with Mel. 

Methylation of methylthiotropone 424a (Scheme 114), according to Seitz and The (87AP362), leads to unstable sulfonium salt 425. This salt can be demethylated and deprotonated (via tropone 426) to give the resonance-stabilized sulfonium ylide 428, accompanied by the product 427 of methyl transfer from 425. Ylide 428 at elevated temperatures undergoes an inter-molecular methyl transfer to yield sulfonium salt 424b. 

Figure 10.2 illustrates selected examples of these epoxide products. Aromatic and heteroaromatic aldehydes proved to be excellent substrates, regardless of steric or electronic effects, with the exception of pyridine carboxaldehydes. Yields of aliphatic and a,/ -unsaturated aldehydes were more varied, though the enantio-selectivities were always excellent. The scope of tosylhydrazone salts that could be reacted with benzaldehyde was also tested (Fig. 10.3) [29]. Electron-rich aromatic tosylhydrazones gave epoxides in excellent selectivity and good yield, except for the mesitaldehyde-derived hydrazone. Heteroaromatic, electron-poor aromatic and a,/ -unsaturated-derived hydrazones gave more varied results, and some substrates were not compatible with the catalytic conditions described. The use of stoichiometric amounts of preformed sulfonium salt derived from 4 has been shown to be suitable for a wider range of substrates, including those that are incompatible with the catalytic cycle, and the sulfide can be recovered quantitatively afterwards [31]. Overall, the demonstrated scope of this in situ protocol is wider than that of the alkylation/deprotonation protocol, and the extensive substrate...

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... 

Irrespective of whether the initially formed sulfonium ion B or the subsequently formed sulfonium ion D reacts with the alcohol, the alcohol is taken up by such a sulfonium ion with formation of sulfuranes A (first case) or C (second case). Any of these sulfuranes would yield the sulfonium salt E after dissociation. Once this sulfonium salt has formed, five equivalents ofNEtj are added to the reaction mixture, which then is allowed to warm up from -60 to -45°C. Under these conditions, the sulfonium salt E is deprotonated to give the sulfonium ylide F. This ylide undergoes a /3-elimination via a cyclic transition state to form the desired carbonyl compound and dimethyl sulfide as a side-product. 

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