Trimethylsulfonium iodide

Compounds 242 when treated with trimethylsulfonium iodide under phase-transfer catalysis (PTC) conditions ( -Bu4XI, dichloromethane, 50% NaOH) provide mixtures of the corresponding 2-oxiranylvinyl benzotriazoles 243 and 18-83% yields of heteropentalenes 244. The ratio of these two main products is highly dependent on the R substituent (Scheme 29) <2004ARK(ii)109>. 

Condensation of the carbonyl group with the yUde from trimethylsulfonium iodide leads initially to an addition product. The anion formed on the carbonyl oxygen then internally displaces dimethyl sulfide to give an oxirane yielding epoxide (114-3). Reaction of that intermediate with a 1,2,4-triazine leads to an epoxide ring opening with the consequent incorporation of the second heterocyclic moiety. There is thus obtained fluconazole (114-4) [125]. 

A structurally unusual 3-blocker that uses a second molecule of itself as the substituent on nitrogen is included here in spite of the ubiquity of this class of compounds. Exhaustive hydrogenation of the chromone (13-1) leads to a reduction of both the double bond and the carbonyl group, as in the case of (11-2). The car-boxyhc acid is then reduced to an aldehyde (13-2) by means of diisobutylaluminum hydride. Reaction of that intermediate with the ylide from trimethylsulfonium iodide gives the oxirane (13-3) via the addition-displacement process discussed earlier (see Chapters 3 and 8). Treatment of an excess of that epoxide with benzylamine leads to the addition of two equivalents of that compound with each basic nitrogen (13-4). The product is then debenzylated by catalytic reduction over palladium to afford nebivolol (13-5) [16]. The presence of four chiral centers in the product predicts the existence of 16 chiral pairs. 

Another total synthesis of sufentanil has been described the cyclization of 2-(2-thienyl)ethylamine with allyl-trimethylsilane and formaldehyde gives 4-hydroxy-1-[2-(2-thienyl)ethyl]piperidine, which is oxidized with oxalyl chloride in DMSO/dichloromethane to 1-[2-(2-thienyl) ethyl]piperidin-4-one. The epoxidation of this compound by means of trimethylsulfonium iodide and the sodium salt of DMSO yields the spiro-epoxide, which is opened with... 

Vinylpolystyrene, a useful intermediate for the preparation of various functionalized supports for solid-phase synthesis [7,57-59], has been prepared by the polymerization of divinylbenzene [7], by Wittig reaction of a Merrifield resin derived phosphonium salt with formaldehyde [59-62], or, most conveniently, by treatment of Merrifield resin with trimethylsulfonium iodide and a base [63] (Figure 5.7). 

Dimethyl sulfide Methyl iodide Trimethylsulfonium iodide (100%)... 

Wit tig, Wittig-Homer, and Knoevenagel reactions These reactions can be carried out with A1203 or KF supported on A1203 without solvent, but addition of water catalyzes both Wittig and Wittig-Homer reactions. Under these conditions trimethylsulfonium iodide undergoes reaction to form epoxides (equation I). 

Dimethylsulfonium methylide. The reagent can be generated conveniently by reaction of NaOH with trimethylsulfonium chloride rather than NaH, required for generation from trimethylsulfonium iodide, the usual precursor.1 An added advantage is that the chloride can be prepared readily by reaction of dimethyl sulfide with methyl chloroformate in 73% yield.2... 

Epoxidation.3 Trimethylsulfonium iodide reacts with aldehydes in the presence of solid KOH in CH3CN to form epoxides in high yield. The reaction with ketones proceeds in lower yields. 

The 7-oxo group of perhydropyrido[l,2-a]pyrazine-l,4,7-trione 130 was converted into an epoxide group with trimethylsulfonium iodide in the presence of rert-BuOK in DMSO, and the separated epoxides 131 and 132... 

With strong bases it is also possible to remove a proton from the methyl group of triarylmethylphosphonium halides, trimethylsulfonium iodide, or trimethylsulfoxonium iodide (Figure 9.1). Here, too, species are produced that are betaines of the ylide type. 

Note Generated in situ from trimethylsulfonium iodide with NaH in DMSO for A, from trimethyloxosul-fonium iodide with NaH in toluene for B, and in THF as solvent with n-BuLi as base for C. 

A number of related reagents have also been prepared, but of these 1 is the most reactive, as judged by reaction of uridine to give 3-methyluridine. One closely related reagent with similar reactivity is trimethylsulfonium hydroxide, (CHslsS OH, prepared by reaction of trimethylsulfonium iodide with silver oxide. ... 

The formation of salts from sulfides is a common process. Thus reaction of dimethyl sulfide with methyl iodide gives trimethylsulfonium iodide (MejS T). 

Prepared by the reaction of n-butyllithium in hexane with trimethylsulfonium fluoroborate "H. Teichmann and G. Hilgetag, Ber., 96, 1454 (1963)] in dimethoxyethane (DME). In this case use of trimethylsulfonium iodide is unsuitable. 

Dimethylsulfonium Methylide. Methylation of dimethylsulfide with methyl iodide produces trimethylsulfonium iodide. The positive charge on sulfur enhances the acidity of the methyl protons so that treatment of the sulfonium salt with a base converts it to dimethylsulfonium methylide. This unstabilized ylide should be used immediately after its preparation. 

The methylene transfer reaction from ylides to ketones has been developed as a convenient synthetic method for obtaining oxiranes [24]. However, the experimental procedure is complex. For example, a THF solution of dimethylsulfonium-methylide (61) is obtained by treatment of trimethylsulfonium iodide (60) with BuLi in THF at 0°C, and after addition of the ketone the mixture is heated at 50-55 °C under nitrogen to yield the oxirane. Throughout the reaction and separation of the product, the organic solvent is essential [25]. 

Carey s procedure. The salt is trimethylsulfonium iodide (I), the base is a solution of sodium methylsulfinylmethide (2), prepared by heating a mixture of powdered sodium hydride (0.1 ra.) with excess DMSO with stirring under nitrogen at 75 ... 

N-Trim ylsilylacetamide, 1232,1235-1236 Trimethylsilyl azide, 1236 l-Triiiiethylsilyl-l,4-dihydropyridine, 1235 O-Trimethylsilyl ethers, 427 Trimethylsulfonium halides, 314, 315 Trimethylsulfonium iodide, 1236 Trimethylsulfoxonium iodide, 1236... 

Scheme 11 Reaction of moiphinan 28 with unstable sulfur ylide to give 29. Reagents and conditions (a) trimethylsulfonium iodide, NaH, THF-DMSO, it, 65% (b) NaH, DMF, 80°C, 61%...

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