Sulfonium ylides, cyclic

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. 

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). 

Aldol addition and related reactions of enolates and enolate equivalents are the subject of the first part of Chapter 2. These reactions provide powerful methods for controlling the stereochemistry in reactions that form hydroxyl- and methyl-substituted structures, such as those found in many antibiotics. We will see how the choice of the nucleophile, the other reagents (such as Lewis acids), and adjustment of reaction conditions can be used to control stereochemistry. We discuss the role of open, cyclic, and chelated transition structures in determining stereochemistry, and will also see how chiral auxiliaries and chiral catalysts can control the enantiose-lectivity of these reactions. Intramolecular aldol reactions, including the Robinson annulation are discussed. Other reactions included in Chapter 2 include Mannich, carbon acylation, and olefination reactions. The reactivity of other carbon nucleophiles including phosphonium ylides, phosphonate carbanions, sulfone anions, sulfonium ylides, and sulfoxonium ylides are also considered. 

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... 

Among the compounds to be discussed in this subsection we also encounter thiabenzene systems that, according to Mislow (168), are best described as cyclic sulfonium ylides. l-Pentafluorophenyl-2-methyl-2-thianaphthalene 130 the first example of an optically active thiabenzene, was prepared by Mislow and co-workers (169) by deprotonation of thiochromenium tetrafluoroborate 131 with brucine in anhydrous dimethylsulfoxide. 

The reaction of a cyclic sulfonium ylide such as dimethylsulfonium-2-oxocyclohexylide (411) with DMAD gives rise to a ring-expanded product, namely, dimethylsulfonium-2,3-dicarbomethoxy-4-oxo-2-cyclooctenylide (414), probably through the intermediates 412 and 413 (Scheme 65). By carrying out the reaction in benzene, it was possible to isolate a compound assumed to be 413, which was subsequently transformed in polar solvents to 414. The reaction of an andogous ylide... 

In an analogous manner, nitroalkenes can be utilized as the electrophile in a tandem coupling-cyclization process (Eq. 2.18). Addition of a stabilized sulfonium ylide such as 209, to a variety of nitroalkenes provides an intermediate nitronic acid, which upon displacement of dimethyl sulfide provides a mixture of the corresponding nitrocyclopropane (XL) and cyclic nitronate (XLI). The ratio of products is highly dependent on the structure of the nitroalkene. For example, without a substituent on the a-position of the nitroalkene (R = H), only the... 

Shift of sulfonium ylide has been applied in organic synthesis as a useful methodology for carbene insertion into a G-S bond. This reaction has been particularly applied in the synthesis of cyclic thioethers, as shown in Equation (19)." " ... 

Ammonium ylides undergo [l,2]-shift in a manner similar to oxonium and sulfonium ylides. A preferentially migrating group is usually a benzyl group. A sequence of intramolecular formation of ammonium ylide and subsequent rearrangement was extensively explored by West and co-workers in the synthesis of cyclic amines. ... 

An example of the photodecomposition of a dithiin to give a stable dithiet, with elimination of ethylene, has been reported.206 A different reaction is preferred in the dithiins (261), which on irradiation, are converted to benzene derivatives (262) via the 1,4-dithiocins (263).207 The cyclic trimer of thio-acetophenone on irradiation in cyclohexane yields thioacetophenone.208 An initial carbon-sulfur bond homolysis is also responsible for the conversion, on irradiation in methanol, of a 3-cephem to two thiazoles,209 whereas a 1,2-alkyl migration followed by a further photochemically induced carbon-sulfur bond homolysis has been proposed to account for the photorearrangement of the sulfonium ylides (264) to the pyrimido-l,4-benzo[h]thiazepines (265).210 The novel photorearrangemenl of a 1,3-thiazine to a cyclopro-pathiazolidine has also been rationalized in terms of an initial carbon-sulfur... 

Reactions of carbocyclic P-keto esters, sulfonium ylides and enamines with activated alkynes such as DMAD are known to result in formation of (n + 2) ring expanded products. In a study of the analogous reactions of carbocyclic p-keto phosphonates, it was found that in the cases of the simple cyclic P-keto phosphonates 1, ring expansion occurred to give 2 in reasonable yield. Extension of the method to the tetralone 3, however, led to formation of two products, the "expected" (n + 2) ring expansion product analogous to 2 (37%), and the lactone 4 (29%). 

Cyclic mixed acetals with pendant diazo ketone side-chains undergo rearrangement to ether-bridged cycloheptane ring systems on treatment with Cu(hfacac)2.118 A Stevens [1,2]-shift of an oxonium ylide gives the major product (62), in some cases accompanied by minor amounts of a product (63) resulting from a [l,2]-shift of a sulfonium ylide. 

Fig. 17.13. Mechanism of the Swern oxidation of alcohols. The actual reagent is an "activated DMSO" (compound B or D), which reacts with an alcohol with formation of A or C, respectively. Dissociation leads to the sulfonium salt E, which is then converted into the sulfonium ylide F after NEt3 addition and raising the temperature from -60 to -45 °C. /3-Elimination via a cyclic transition state generates the carbonyl compound and dimethyl sulfide from F.

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. 

Comparable cis/trans selectivities and similar conformational effects on them were studied in ring enlargements of cyclic sulfonium ylides. ° Rearrangements of sulfur ylides performed in repetition were used for stepwise ring expansion 5- 8—> 11- —> 14- - 17-membered. ° Synthesis applications of... 

One more carbene-based route to oxapenam derivatives utilizes the Cu-catalyzed decomposition of diazo compounds 547 via cyclic sulfonium ylide 548. The protocol is effective for 5-aryl (80H1999) and 5-heteryl-substituted (82H1597) diazo compounds of type 547. Oida and co-workers succeeded in obtaining oxapenam 549 (33%) by Cu(acac)2-catalyzed transformation of 5-alkenyl-substituted diazo ketones 550. The attempted synthesis of... 

Flash vacuum pyrolysis of 629 affords 630 in 15% yield together with other products [85JA(107)8297]. The reaction of trithiapentalenes with diphenylcarbene gives sulfonium ylides that undergo rearrangement followed by formation of 1,3-dithiins 631 (83CJC1161). The carbenoid, generated by catalytic decomposition of diphenyldiazomethane, reacts with cyclic... 

The epoxy sulfones were prepared by exhaustive peracid oxidation of the corresponding alkene sulfides. These were generated by ring expansion of cyclic 1-methyl-2-vinyl sulfonium salts 1 via 2,3-sigmatropic rearrangement of the methanides. From the five-membered sulfonium ylide la, (Z)- and ( )-thiacyclooct-4-enes 2 were obtained as an 85 15 mixture. Their chromatographic separation turned out not to be feasible due to concomitant EjZ isomerization on the silica gel column. Since the separation of these epoxy sulfone mixtures obtained by exhaustive oxidation also proved unsuccessful, it was found expedient to first oxidize the mixture of sulfides to an alkene sulfone mixture ( )-3, which could be separated and eventually epoxidized into epoxides cis- and trans-4 and cis- and trans-5. 

Reactions of cyclic [i-ono sulfonium ylides with 2,3-diphenylcyclopropenethione produced 3,4-diphenyl-2//-pyran-2-thiones 3 and 4. ... 

Recently, the sulfonium-ylide pathway has been used repeatedly to perform one-carbon ring expansion by formal insertion of a carbene moiety into a C—S or N—S bond of a cyclic sulfur compound. Examples are compiled in Scheme 37. It can be seen that ring enlargement was successful with thiochroman-4-ones 345 and 348,... 

Sulfur and ammonium ylides are susceptible to [2,3]-sigmatropic rearrangements under mild conditions with efficient transfer of chirality, as Trust and Ham-men showed in 1973 [1626], Most of the applications of these rearrangements have been conducted on chiral synthons [1622]. Kurth and coworkers [1627, 1628] have applied this reaction to the synthesis of P-chiral, y,8-unsaturated acids via the rearrangements of cyclic sulfonium ylides 10.21, starting from thiol 10.22 (Figure 10.9). 

Sulfonium ylides were generated by treatment with a cyclic or an acyclic sulfide in the presence of a base. For example, Tang and coworkers generated a sulfonium ylide from corresponding benzylic halide 31 and tetrahydrothiophene 32, and effectively formed bicyclic cyclopropanes... 

---