Sulfonium cyclic

Allylic amine is a less reactive leaving group[7], but the allylic ammonium salts 214 (quaternary ammonium salts) can be used for allylalion(l30,131]. Allylic sulfonium salts are also used for the allylation[130]. The allylic nitrile in the cyclic aminonitrile 215 can be displaced probably via x-allylic complex formation. The possibility of the formation of the dihydropyridinium salts 216 and subsequent conjugate addition are less likelyfl 32],... 

Electrophilic attack on the sulfur atom of thiiranes by alkyl halides does not give thiiranium salts but rather products derived from attack of the halide ion on the intermediate cyclic salt (B-81MI50602). Treatment of a s-2,3-dimethylthiirane with methyl iodide yields cis-2-butene by two possible mechanisms (Scheme 31). A stereoselective isomerization of alkenes is accomplished by conversion to a thiirane of opposite stereochemistry followed by desulfurization by methyl iodide (75TL2709). Treatment of thiiranes with alkyl chlorides and bromides gives 2-chloro- or 2-bromo-ethyl sulfides (Scheme 32). Intramolecular alkylation of the sulfur atom of a thiirane may occur if the geometry is favorable the intermediate sulfonium ions are unstable to nucleophilic attack and rearrangement may occur (Scheme 33). 

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. 

Cyclic sulfonium ions were observed in hydrolysis... 

A well-known characteristic of medium-sized rings (8- to 11-membered) is their ability to undergo facile transannular reactions. Cere et al. found that acid-catalyzed transannular cyclizations of 8-10-membered 7,5-unsaturated cyclic sulfides yield fused bicyclic sulfonium salts independently of the geometry of the double bond <1998J(P2)977>. 

Transannular cyclizations of nine-membered cyclic sulfides provided a novel route to thioanalogues of swainsonine derivatives. Treatment of the enantiopure polyhydroxylated thiacyclononane derivative 48a with trimethylsilyl iodide yielded the bicyclic sulfonium salt 49a as a single diastereomer, as shown in Equation (16) <2003JOC3311 >. The presence of a C2-axis and the complete regio- and stereoselectivity of the transannular substitution led to a single configurationally homogeneous product irrespective of the fact that the sulfur atom would attack C-5 or C-6. 

Pinto and co-workers have synthesized various thioniabicyclo[4.3.0]nonanes via a protocol that involves intramolecular displacement of a leaving group on a pendant acyclic chain by cyclic thioethers. A sulfonium ion analogue 54 of swainsonine <2006CAR1685> and an analogue 55 of epi-swainsonine <2006JOC1262>, which differs from swainsonine in the stereochemistry at C-3, were synthesized using this approach. 

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... 

Direct oxidation of bis-sulfides by trifluoromethanesulfonic anhydride was suggested only recently.57 For example, treatment of 10 with triflic anhydride affords the corresponding dication salt 34 in high yield via intermediate formation of a sulfonyl sulfonium salt 33.58 A number of other cyclic and acyclic bis-sulfides 35 undergo facile oxidation to dications under these conditions (Scheme ll).57... 

Optically active sulfonium and selenonium salts are well known and the stereochemistry of the isomers has been studied.1 3 Optically active cyclic diaryl(alkoxy)-sulfonium salts 14, 15, and 16, stabilized by intramolecular sulfur-oxygen interaction, were synthesized in 2000 by reacting optically active spirosulfuranes with trimethyloxonium tetrafluoroborate.29 The absolute configurations were assigned on the basis of the reaction mechanism. The sulfonium salts were hydrolyzed in KHC03aq. to yield optically active sulfoxides in over 86% ee (Scheme 7). 

The numerous straightforward examples of internal displacement reactions leading to isolable cyclic products will not be discussed here, but only, for the most part, those ionization reactions in which a cyclic intermediate or transition state is deduced from the rearranged structure of the product. A well-known example is mustard gas and other alkyl chlorides with sulfur on the /3-carbon atom. Although mustard gas is a primary and saturated alkyl chloride, its behavior is like that of a typical tertiary alkyl chloride. It reacts so fast by a first order ionization that the rate of the usual second order displacement reaction of primary alkyl halides is not measureable. Only the ultimate product, not the rate, is determined by the added reagent.228 Since the effect of the sulfur is too large to be explicable in terms of a carbon sulfur dipole or similar explanation, a cyclic sulfonium ion has been proposed as an... 

Cyclisation of an NH amide toward a cyclic thionium ion was described for the synthesis of a tetrahydropyrrolo-[l,2-tf]pyrimidine-2,6(l//,7//)-dione 351. Compound 349 was transformed to 351 in two steps. The first one is the formation of a transient alkylthio-substituted lactam 350 from amidothioacetal 349 in the presence of dimethyl-(methylthio)sulfonium tetrafluoborate (DMTSF) followed by intramolecular cyclization <2000JOC235>. 

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 their important work on the synthesis and properties of optically active chlorosulfurane (+)-177, Martin and Balthazor (195) deduced its absolute configuration by means of chemical correlations. Reaction of (+)-l 77 with silver tetrafluoroborate yields cyclic sulfonium salt 198, which was hydrolyzed without isolation under alkaline conditions to give sulfoxide (-)-(5 -180, from which (+)-177 was obtained. Assuming that the conversion (+)-l 77 -> 198 proceeds with... 

Analysis of residue after removing cyclic oligomer. TAS =Tris(dimethylamino)sulfonium. 

A type I one-electron photo-oxidation of methionine-methionine-containing peptides by triplet carboxybenzophenone in air-saturated aqueous solution has been reported the S+ radical cation that is formed then reacts with the other Met-S to form an S-S three-electron complex which reacts with superoxide radical anion before hydrolysis to Met(=0)-Met(=0) bis-sulfoxide. Alternatively, cyclization of the A-terminal NH2 on to the S can occur to give a three-electron S-N complex which can react with superoxide radical anion to give a cyclic sulfonium intermediate. 

The acid-catalysed transannular cyclization of 8-10-membered y,5-unsaturated cyclic sulfides (59) or (60) yields c/x-fused bicyclic sulfonium salts (61) independently of the geometry of the double bond. The rate varies linearly with the acidity function -(Ho h with a slope of 1. The rate variations span a range of about 10 , the maximum rate difference being observed for the ( /Z)-thiacyclooct-4-ene pair. The data are consistent with the classical interpretation of the intramolecular reactivity in terms of internal strain of the substrate and/or of the transition state. ... 

The polymerization of LXIII, a stable isolable zwitterion, on heating or photolysis involves nucleophilic attack by phenoxide anion on the cyclic sulfonium ring [Hoyle et al., 2001 Odian et al., 1990]. The reaction proceeds as a step polymerization. 

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... 

Reaction of benzyl a-D-glucopyranosyl cyclic sulfate 44 or benzyl a-D-galactopyranosyl cyclic sulfate 45 with 1,4-anhydro-2,3,5-tri-0-benzyl-4-thio-D-arabinol 46, followed by debenzylation and reduction, gave novel sulfonium sulfate derivatives 47a and 47b, respectively, which were used to prepare homologs of salacinol 48, a natural human maltase glucoamylase inhibitor, as lead candidates for the treatment of type 2 diabetes (Scheme 3) <2006JOC1111>. 

A mixture of 1 mmol of optically active sulfonium salt, 1 mmol of cyclic /J-oxo ester and 1.3 mmol of anhyd potassium carbonate is stirred in 10 mL of CH2C12 at r.t. for 2 d. After filtration of insoluble materials, the alkylated products are purified by preparative TLC (Merck, silica gel 60F254) and medium-pressure column chromatography. The ee is determined by H NMR analysis [Eu(hlc)3] or by HPLC (Oaicel Chiralcel CA-1. methanol). 

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. ... 

The volatility of difunctional isocyanates (such as tolylene diisocyanates, hexamethylene diisocyanate, etc.) creates many environmental problems in the urethane industry. These difficulties can be overcome by preparation of NCO-terminated oligomers with low vapor pressure. One approach is the preparation of NCO-ter-minated oligomers by partial cyclotrimerization of difunctional isocyanates. Usually this is achieved by a multi-step process which includes also deactivation of the catalyst at a certain conversion. During our work on cyclotrimerization of isocyanates we found that cyclic sulfonium zwitterions are very active cyclotrimerization catalysts (2). Recently we found that cyclic sulfonium zwitterions under certain reaction conditions act as anionic initiators. This behavior of cyclic sulfonium zwitterions permits preparation of isocyanate oligomers containing isocyanurate rings by a one-step procedure, eliminating the deactivation step. 

In this communication this unusual behavior of cyclic sulfonium zwitterions will be discussed. 

The kinetics of catalysis of cyclotrimerization was studied on the model system phenyl isocyanate/ace-tonitrile (solvent). Acetonitrile (AN, 99.64%, from Vinstron Corp.) was purified by refluxing with phosphorus pentoxide (5 g/1), then with calcium hydride (2 g/1) followed by distillation under nitrogen. Phenyl isocyanate was obtained from the Upjohn Company with a purity of 99.5%, and was purified by distillation. Tolylene diisocyanates (2,4 and 80/20 2,4/2,6 isomers) were obtained from the Mobay Chemical Co., and were purified by distillation. Cyclic sulfonium zwitterions (SZ) were obtained from the Dow Chemical Co. 

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