2-Lithio-2-trimethylsilyl- 1,3-dithiane

Multicomponent linchpin couplings can be carried out with 2-trialkylsilyl substituted 1,3-dithianes 207 and epoxides and was successfully used in the synthesis of natural products182. Tietze and coworkers303 found out that 2-lithio-2-trimethylsilyl-1,3-dithiane 208 reacted with two equivalents of a chiral epoxides in the presence of a crown ether to give first the monoadduct 209, which suffered 1,4-Brook rearrangement304 generating a new dithiane anion 210. Final reaction with an epoxide afforded products 211, which are equivalents of acetone aldol products (Scheme 60). 

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... 

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. 

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>. 

The lithiation of 1,3-oxathiane (296) takes place with s-BuLi at —78 °C to give 2-lithio-1,3-oxathiane (315), an analogue of 2-lithio-l,3-dithiane (161), but with lower stability487. This intermediate reacts with different electrophiles, such as alkyl halides, carbonyl compounds, benzonitrile, dimethyl disulfide, dimethyl diselenide, trimethylplumbyl acetate and trimethylsilyl, germyl and stannyl chlorides488,489. However, further deprotection of 2-substituted 1,3-oxathianes has not been reported yet. 

Related Reagents. Benzothiazole Carbon Monoxide A, A -Diethylaminoacetonitrile iVJV-Dimethyldithiocarbamo-ylacetonitrile 2-Lithio-l,3-dithiane Methylthiomethyl p-Tolyl Sulfone 2- Trimethylsilyl)thiazole. 

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... 

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... 

Ketene thioacetals also are readily availabte > by a Wittig-type reaction of 2-lithio-2-trimethylsilyl-l,3-dithiane (61) with aldehydes or... 

Acyl Anion Conjugate Additions. The lithio reagent readily undergoes 1,4-addition to unsaturated substrates (eq 6), in direct contrast to the corresponding 2-lithio-2-trimethylsilyl-l,3-dithiane, which is a poor Michael donor. The initial Michael adducts can also be alkylated to provide highly functionalized products. Very good levels of diastereoselectivity have been observed in the 1,4-addition and enolate alkylations of cyclic enoates (eq 7)2 and acyclic enones (eq 8). ... 

Related Reagents. 2-Trimethylsilyl-l,3-dithiane 2-lithio-l, 3-dithiane 1,3-dithiane. 

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. 

One Carbon Homologation of Aldehydes via a Peterson Olefination. 2-Trimethylsilyl-l,3-dithianes have been widely used in the formation of thioketene acetals. This reaction is the first of a two-step procedure that results in the one carbon homologation of an aldehyde or ketone via a 2-lithio-2-TMS-1,3-dithiane-mediated Peterson olefination, followed by hydrolysis of the dithiane to give the corresponding ester (eq 20). ... 

Formation of l,5-bis(acylsilanes) was achieved via exposure of 2-lithio-2-TMS-l,3-dithiane to 1,3-dihalopropanes. Dithiane removal followed by treatment with PTSA then provides the 2,6-bis-trimethylsilyl-4//-pyran (eq 33). ... 

Lithio-2-trimethylsilyl-l,3-dithiane is the most widely utilized reagent for the conversion of ketones and aldehydes to the corresponding ketene dithioacetals (Scheme 2.49) [126-128]. It is used for the synthesis of functionalized 2-alkylidene-1,3-dithianes 79 [129-135]. The 2-alkylidene-l,3-dithianes 79 thus synthesized are useful synthetic intermediates, which are conveniently accessible by means of Peterson reactions, and they can be transformed into various compounds [136, 137]. For example, compounds 79 are converted to the corresponding carboxylic acids, aldehydes, and enones by hydrolysis, hydrogenation followed by hydrolysis, and deprotonation followed by alkylation and hydrolysis, respectively (Scheme 2.49) [138-140]. 

On the other hand, the reactions of 2-lithio-2-trimethylsilyl-l,3-dithiane with esters and thioesters give not the ketene dithioacetals, but the 2-acyl-l,3-dithianes 81 (Scheme 2.50). The possibly formed silyl enol ethers 80 undergo subsequent hydrolysis to give 81 [141],... 

Scheme 2.50. Reaction of 2-lithio-2-trimethylsilyl-l, 3-dithiane with esters and thioesters.

Vol. E 19d (ed M. Hanack), Thieme, Stuttgart, pp. 958-1016 To give an example, l-lithio-l-trimethylsilyl-1,3-dithiane undergoes a 1,2-addition... 

The reaction of 2-lithio-2-trimethylsilyl-l,3-dithian (94) with aldehydes and ketones is apparently the method of choice for the synthesis of ketone... 

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