Sulfonium ylides examples

Stereoselective epoxidation can be realized through either substrate-controlled (e.g. 35 —> 36) or reagent-controlled approaches. A classic example is the epoxidation of 4-t-butylcyclohexanone. When sulfonium ylide 2 was utilized, the more reactive ylide irreversibly attacked the carbonyl from the axial direction to offer predominantly epoxide 37. When the less reactive sulfoxonium ylide 1 was used, the nucleophilic addition to the carbonyl was reversible, giving rise to the thermodynamically more stable, equatorially coupled betaine, which subsequently eliminated to deliver epoxide 38. Thus, stereoselective epoxidation was achieved from different mechanistic pathways taken by different sulfur ylides. In another case, reaction of aldehyde 38 with sulfonium ylide 2 only gave moderate stereoselectivity (41 40 = 1.5/1), whereas employment of sulfoxonium ylide 1 led to a ratio of 41 40 = 13/1. The best stereoselectivity was accomplished using aminosulfoxonium ylide 25, leading to a ratio of 41 40 = 30/1. For ketone 42, a complete reversal of stereochemistry was observed when it was treated with sulfoxonium ylide 1 and sulfonium ylide 2, respectively. ... 

Since cbiral sulfur ylides racemize rapidly, they are generally prepared in situ from chiral sulfides and halides. The first example of asymmetric epoxidation was reported in 1989, using camphor-derived chiral sulfonium ylides with moderate yields and ee (< 41%) Since then, much effort has been made in tbe asymmetric epoxidation using sucb a strategy without a significant breakthrough. In one example, the reaction between benzaldehyde and benzyl bromide in the presence of one equivalent of camphor-derived sulfide 47 furnished epoxide 48 in high diastereoselectivity (trans cis = 96 4) with moderate enantioselectivity in the case of the trans isomer (56% ee). ... 

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]. 

A more direct access to the unstable and non isolated sulfonium ylides 58a- c is the reaction of diisopropyl diazomethylphosphonate 57 with allylic sulfides, catalyzed by Cu(II), Rh(II) [39], or ruthenium porphyrins.[40] For example, the a-phosphorylated y,d-unsaturated sulfides 59-61 are obtained through the [2,3] -sigmatropic rearrangement of 58a-c. This method allows the use of a greater variety of starting allylic sulfide substrates, such as 2-vinyl tetrahydrothiophene, or propargylic sulfides (Scheme 15). 

The rearrangements of allylic sulfoxides, selenoxides, and amine oxides are an example of the first type. Allylic sulfonium ylides and ammonium ylides also undergo [2,3]-sigmatropic rearrangements. Rearrangements of carbanions of allylic ethers are the major example of the anionic type. These reactions are considered in the following sections. 

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... 

Interaction of an electrophilic carbene or carbenoid with R—S—R compounds often results in the formation of sulfonium ylides. If the carbene substituents are suited to effectively stabilize a negative charge, these ylides are likely to be isolable otherwiese, their intermediary occurence may become evident from products of further transformation. Ando 152 b) has given an informative review on sulfonium ylide chemistry, including their formation by photochemical or copper-catalyzed decomposition of diazocarbonyl compounds. More recent examples, including the generation and reactions of ylides obtained by metal-catalyzed decomposition of diazo compounds in the presence of thiophenes (Sect. 4.2), allyl sulfides and allyl dithioketals (Sect. 2.3.4) have already been presented. 

The sulfonium ylide derived chemistry of penicillins continues to meet the interest of several research groups. It is well known that intermolecular carbenoid attack at the sulfur atom generates a sulfonium ylide which undergoes spontaneous opening of the thiazolidine ring to furnish a l,2-sm>-penicillin 326). Novel examples of this reaction type were found upon Rb2(0Ac)4-catalyzed decomposition of diazomalonic esters in the presence of various penicillins this transformation constituted the opening step of a synthetic sequence directed towards 2-alkoxycarbonyl-cephems 345 a) or modified penicillins 345 b). Similar to its reaction with 4-thio-2-azetidinone... 

Another example has been provided by Ito et al., who described the use of methanofullerene derivatives as powerful and stable precursors for glycofullerenes.217 Their study was based on the use of [60]fullerenoacetyl chloride (227), obtained from the ferf-butyl [60]fullerenoacetate derivative 226, which had been prepared in 56% yield by treatment of corresponding stabilized sulfonium ylides 225 with C6o-218 Subsequent transformation with p-TsOH in toluene gave [60]full-erenoacetic acid, which was directly converted into the corresponding acyl chloride 227 by using thionyl chloride. Standard ester formation with methyl 2,3,4-tetra-O-benzyI -/<-d-gl ucopyranoside (228) and 4-(dimethylamino)pyridine (DMAP) afforded the desired hybrid derivative 229 in 66% yield. 

The availability of cyclopentenones from butanolides allows the lactone annulation to facilitate the synthesis of cyclopentyl natural and unnatural products. An example that highlights the latter is dodecahedrane (178) for which 179 constitutes a critical synthetic intermediate 136,137). Lateral fusion of cyclopentenones as present in 179 can arise by acid induced reorganization and dehydration of 180. While a variety of routes can be envisioned to convert a ketone such as 182 into 180, none worked satisfactorily137 On the other hand, the cyclobutanone spiro-annulation approach via 181 proceeds in 64 % overall yield. Thus, the total carbon cource of dodecahedrane derives from two building blocks — cyclopentadiene and the cyclopropyl sulfonium ylide. 

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. 

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... 

As a final example of regioselective control (Scheme 25), sulfonium ylides usually give nitrones when reacted with nitroso groups via oxaziridine intermediates. However, 7-aryl-2-dimethylamino-3,4,5,6-tetrahydropteridine-4,6-diones 120 were directly formed when nitrosopyrimidine 121 reacted with dimethylphenacylsulfonium bromides 122 instead of the isomeric 5-oxides <1996H(43)437>. It was also reported that the resulting pteridines were reduced to give 7,8-dihydro derivatives 123 with sodium dithionite (Table 7). 

The synthetic utility of a-phosphorus- and a-thio-stabilized carbanions is the subject of numerous reviews.21 Notable are additions of phosphonium ylides (237),183 sulfonium ylides (238),l84 ° oxosulfo-nium ylides (239)184 " and sulfoximine ylides (240)184,1 to electron-deficient alkenes which afford nucleophilic cyclopropanation products. In contrast, with a-(phenylthio)-stabilized carbanions, which are not acyl anion equivalents, either nucleophilic cyclopropanation or retention of the hetero substituent occurs, depending on the acceptor and reaction conditions used. For example, carbanion (241) adds to 1,1-... 

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... 

Only a limited number of examples have been reported. The reactivity of sulfonium ylide 98a, prepared by the reaction of thiepine 96 and dimethyl diazomalonate (Section 13.03.6.1), was examined <20060BC2218>. The reactivity of the stabilized sulfonium ylide 98a was restricted to the highly reactive Michael acceptor, tetracya-noethylene 152 (the ylide failed to react with benzaldehyde or dicyanoethylene). Reaction of ylide 98a with tetracyanoethylene 152 led to the consumption of the ylide 98a (Equation 22). Thiepine 96 was produced in the reaction and the formation of cyclopropane 153 was suggested. 

Iodonium ylides (136), generated in situ with bisacetoxyiodobenzene, are converted to allyl- or benzyl-substituted oxonium or sulfonium ylides (137) via rhodium- or copper-catalysed carbene transfer.115 Such ylides undergo [1,2]- or [2,3]-rearrangement to the corresponding 2-substituted heterocycles (138). An example of the rhodium-catalysed reaction is reported in Scheme 36. 

The greater stability of sulfoxonium compared to sulfonium ylides and the associated consequence that product-development control influences, which of several conceivable zwitterionic intermediates is formed preferentially, is also noticeable in reactions of S ylides with a,/3-unsaturated carbonyl compounds. This can be seen in Figure 9.5 using the example of two reactions with cyclohexenone. Because of product-... 

Some specific examples of the formation of sulfur ylides by the deprotonation of sulfonium salts are shown in Scheme 2. The abstraction of a proton from the corresponding sulfonium salt as shown in Schemes 1 and 2, is the most common procedure for the generation of sulfur or sulfonium ylides however, the most direct synthesis of sulfur ylides (2a) involves addition of a sulfide to a carbene (5),... 

Starting from (2-oxoalkylidene)sulfur-5, triacylcyclopropanes are often the dominant products, regardless of the decomposition mode of the sulfonium ylide. . In fact, no example of an efficient alkene cyclopropanation using these synthetic equivalents of oxocar-benes is yet known. The photochemical decomposition (2> 300nm) of (2-oxo-2-phenylethylidene)sulfur-5" in cyclohexene yielded only a minor amount of 7-benzoyl-bicyclo[4.1.0]heptane (2, 5%) in addition to tranj-l,2,3-tribenzoylcyclopropane (3, 40%), acetophenone (37%), bicyclohex-2-enyl (38%), and propiophenone (3%). In an inert solvent (benzene, chloroform) without an additional trapping reagent,, 2,3-tribenzoylcyclo-... 

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,... 

The diastereofacial selectivity of sulfonium ylides and related reagents has been shown in many examples, in particular with steroidal enones16. The bicycloenone 19 is attacked by dimethyl-sulfoxonium melhylide from the less hindered side to give the ent/o-cyclopropanc derivative 20 in 85% yield31. 

Another example of the C + C=N" pathway involves the addition of stabilized sulfonium ylides onto A-tosylimines. This is operationally a straightforward procedure under phase-transfer conditions <97TL7225>, and the use of a chiral auxiliary allows the preparation of enantiomerically enriched aziridines, as illustrated by the reaction of A -sulfonylimine 132 with chiral sulfonium propargylide 133 to give the chiral aziridine 134 <97AG(E)1317>. 

In sulfonium ylides, two examples have documented that they too are capable of undergoing a elimination to carbenes under photol5dic, but not thermal, conditions. Dimethylsulfoniumphenacylide, 17, yields a mixture of 7-benzoylnorcarane and acetophenone (by hydrogen abstraction from... 

Dimethylsulfonium methylide and dimethylsulfoxonium methylide also differ in their reachons with a,p-unsaturated carbonyl compounds. The sulfonium ylide reacts at the carbonyl group to form an epoxide, but with the sulfoxonium ylide a cyclopropane derivative is obtained by Michael addihon to the carbon-carbon double bond. The difference is again due to the fact that the kinehcally favoured reachon of the sulfonium yhde with the carbonyl group is irreversible, whereas the corresponding reaction with the sulfoxonium yhde is reversible, allowing preferenhal formahon of the thermodynamically more stable product from the Michael addihon. For example, the cyclopropane 112 is obtained from the reaction of dimethylsulfoxonium methylide with the enone 111 (1.105). Other methods for the formahon of cyclopropanes include carbene and Simmons-Smith-type... 

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