Trimethylsilyl-l,3-dithiane

Preparative Method prepared by alkylation of 2-lithio-l,3-dithiane with chlorotrimethylsilane (eq 1).  

A variation of this method has also been developed for cases in which reactions with (1) give poor results (eq 6). Thus the carbonyl compound is treated with 2-lithio-l,3-dithiane followed by TMSCl to generate the silyl ether. Subsequent addition of a second equivalent of n-butyllithium effects alkenation, affording the thioketene acetal in good yield.  

2-Lithio-2-trimethylsilyl-l -dithiane. This reagent (1) is generated from the title compound by treatment with n-butyllithium at —78 °C (eq 2) and is the species utilized in many of the following transformations. 

Thioketene Acetals. Anion (1) reacts with aldehydes and ketones to provide the corresponding thioketene acetals aryl and unsaturated aldehydes and ketones are good substrates for this reaction (eqs 3 and 4). Enolizable alkyl ketones also react to provide thioketene acetals (eq 5). Alternative methods for the preparation of these cyclic thioketene acetals involve the use of phospho-nate derivatives, mixed zinc-titanium organometallic reagents, and iV,iV-dimethyl thioamides. The phosphonate reagents are more nucleophilic than (1) and are superior when competitive deprotonation is a problem. 

Cationic and Anionic Cyclizations. The thioketene acetals derived from the reaction of anion (1) have found several applications in cyclization methodology. The thioketene acetals can be used as either electrophiles (eq 7) or nucleophiles (eq 8) in a cyclization process which depends on the experimental conditions. 

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When 2-lithio-2-(trimethylsilyl)-l,3-dithiane,9 formed by deprotonation of 9 with an alkyllithium base, is combined with iodide 8, the desired carbon-carbon bond forming reaction takes place smoothly and gives intermediate 7 in 70-80% yield (Scheme 2). Treatment of 7 with lithium diisopropylamide (LDA) results in the formation of a lactam enolate which is subsequently employed in an intermolecular aldol condensation with acetaldehyde (6). The union of intermediates 6 and 7 in this manner provides a 1 1 mixture of diastereomeric trans aldol adducts 16 and 17, epimeric at C-8, in 97 % total yield. Although stereochemical assignments could be made for both aldol isomers, the development of an alternative, more stereoselective route for the synthesis of the desired aldol adduct (16) was pursued. Thus, enolization of /Mactam 7 with LDA, as before, followed by acylation of the lactam enolate carbon atom with A-acetylimidazole, provides intermediate 18 in 82% yield. Alternatively, intermediate 18 could be prepared in 88% yield, through oxidation of the 1 1 mixture of diastereomeric aldol adducts 16 and 17 with trifluoroacetic anhydride (TFAA) in... 

Methoxytrimethylsilane, 123 Methyl acetoacetate, 92 Methyl bromoacetate, 107 Methyl 11-hydroxyundecanoate, 58 Methyl lithium, 27,28 Methyl 10-undecenoatc, 58 2-MethyM,3-dithiane, 81 (V f ,55)-Methyl-3-phenyldimethyl-silyl-3-phenylpropionic acid. 53-4 2-Methyl-3-Phenylprop-2-enal, 111 2-Methyl-2-trimethylsilyl-l,3-dithiane, 81 2-Methyl-l-(trimethylsilyloxy)cydo-hex-l-ene, 100,109 2-Methyl-l-trimethylsilyloxy-cyclo-hex-6-ene, 100... 

Enantiopure 77 was easily prepared by treatment of 2-trimethylsilyl-l,3-dithiane 75 and chiral epoxides 76 in a sequential addition in the presence of a crown ether. In this sequence, a monosUylated 1,5-diol 77 is obtained, allowing a discrimination of the two... 

Thermolysis of 2-diazo-l,3-dithiane, prepared in situ from the reaction of 2-lithio-2-trimethylsilyl-l,3-dithiane and tosyl azide, occurs already below 0°C. The resulting carbene dimerizes efficiently even in the presence of alkenes and alkynes to give bis(l,3-dithianylidene) in 78% yield (Scheme 41) <1997T9269>. 

Chiral /J-amino acyl silanes have been prepared through the addition of 2-lithio-2-trimethylsilyl-l,3-dithiane to enantiomerically pure A-tosylaziridines followed by mercury-mediated thioacetal hydrolysis113. 

An anionic 1,4-migration from C to C was also observed during the lithiation of 2-trimethylsilyl-l,3-dithiane derivatives 221 (equation 144)354. 

The ketenethioacetal (277), prepared from the aldehyde (275) and 2-lithio-2-trimethylsilyl-l,3-dithiane (276), upon treatment with tributyltin hydride gave, via a radical tandem cyclization, the 2-(3-thiol-l-propyl)thieno[3,2-b]thiophene (278) (Scheme 19) <93TL5653>. 

Trimethylsilyl-l,3-dithianes can also serve as masked carboxyl groups. The principle is exemplified by the transformations shown in Scheme 2.124 that form part of a synthesis of the [Uactam antibiotic Thienamycin.252... 

Ketene dithioacetals, available by the Peterson olefination of 2-trimethylsilyl-l,3-dithiane with aldehydes and ketones, are oxidised to the /rara-l,3-dithiane 1,3-dioxides 44 with virtually complete diastereo- and enantioselectivity using Sharpless methodology <03JOC4087>. 

Preparation. The reagent is prepared in c.s.sentially quantitative yield by the reaction of 2-lithio-l,3-dithiane (2, 182-183) in THF with freshly distilled trimethyl-chlorosilane at - 55. The mixture is kept at this temperature for 20 min. and then for 5 hr. at 20°. On treatment with water the reagent is converted into 2-trimethylsilyl-l,3-dithiane. 

Vinylketene thioaeetais. 2-Lithio-2-trimethylsilyl-l,3-dithiane (1) also reacts with 3,/8-unsalurated aldehydes and ketones exclusively with the carbonyl group to give vinylketene thioaeetais (2). These undergo Dicls-Alder cycloaddition, which Carey and... 

The successive reaction of (dibromomethyl)silanes with LDA (hthium diisopropyl-amide) and two equivalents of benzaldehyde gives 1,3-diol monosilyl ethers in good yield (Scheme 10.221) [574]. This tandem reaction would proceed via anionic 1,3-silyl migration of /l-lithioxyalkylsilane intermediate 152 and addition of the resulting lithium carbenoid to benzaldehyde. Thus, internal activation of the silicon-lithium alkoxide promotes nucleophilic addition of a-haloalkylsilanes. Similar tandem reactions of 2-trimethylsilyl-l,3-dithiane with aldehydes [575] and epoxides [576] have been reported. 

To a solution of 2-methyl-l,3-dithiane (34.1 mmol) in THF (150 ml), cooled to — 30 °C, was added n-BuLi (34.1 mmol, 1.5 m in hexane) dropwise (3-5 ml/min). The resulting solution was stirred at —30 to — 20 °C for 1.5 h, and then TMSC1 (37.1 mmol) was added dropwise. After 2.5 h at — 25 °C, water (15 ml) was added, then most of the THF was removed in vacuo. Water and pentane were added, the layers were separated, and the aqueous layer was extracted thoroughly with pentane. The combined organic layers were washed with water, aqueous KOH (10%) and water, and dried. Concentration and distillation gave 2-methyl-2-trimethylsilyl-l,3-dithiane (26.8 mmol, 78%), b.p. 102°C/9.5mmHg. 

A mixture of 2-methyl-2-trimethylsilyl-l,3-dithiane (121 mmol), mercury(n) chloride (266mmol), and mercury(n) oxide (181 mmol) in methanol (225 ml) and water (25 ml) was stirred vigorously and heated under reflux for 2 h. It was then cooled and filtered, and the precipitate was... 

Carbanion generation. A 1 1 mixture of CsOH and CsF suspended in dichloromethane or THF is very effective for generation of carbanions from 1-trimethyl-silylalkynes, 2-trimethylsilyl-l,3-dithiane, trifluoromethyltrimethylsilane, and silyl enol ethers, all through desilylation. 

CYCLIZATION n-Butyllithium. Hydrobromic acid. Hydrogen fluoride. Ion-exchange resins. 2-Lithio-2-trimethylsilyl-l,3-dithiane. Lithium diisopropylamide. Polyphos-phoric acid. Tetra-n-butylammonium iodide. Stannic chloride. Trifluoroacetic... 

The displacement of primary iodides in some carbohydrate derivatives by lithiated 2-trimethylsilyl-l,3-dithiane followed by hydrolysis of the dithioacetal has allowed the synthesis of some acylsilanes (e.g. 21 from 20), and a review on the oxidation of the carbon-silicon bond has included a number of carbohydrate examples. ... 

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