Tetrahydrothiophene, synthesis from

Several approaches have been tried in order to facilitate the conversion process and lower the conversion temperatures, e. g. by using appropriate sulfonium groups (tetrahydrothiophene derivatives) and/or different counter ions. With chloride as a counter ion [80], the synthesis of 2,5-dimethoxy-PPV can be performed at room temperature starting from the corresponding dimethylsulfon-ium polyelectrolyte precursor. 

In contrast, synthesis of 3,4-diphosphorylthiophenes requires more elaboration because of low reactivity of 3,4-positions of thiophene and unavailability of 3,4-dihalo or dimetallated thiophenes. Minami et al. synthesized 3,4-diphosphoryl thiophenes 16 as shown in Scheme 24 [46], Bis(phosphoryl)butadiene 17 was synthesized from 2-butyne-l,4-diol. Double addition of sodium sulfide to 17 gave tetrahydrothiophene 18. Oxidation of 18 to the corresponding sulfoxide 19 followed by dehydration gave dihydrothiophene 20. Final oxidation of 20 afforded 3,4-diphosphorylthiophene 16. 3,4-Diphosphorylthiophene derivative 21 was also synthesized by Pd catalyzed phosphorylation of 2,5-disubstituted-3,4-dihalothiophene and converted to diphosphine ligand for Rh catalysts for asymmetric hydrogenation (Scheme 25) [47],... 

The synthesis of pure metalacycle la from [Ir(COD)Cl]2 and LI requires only amine base and heat, followed by precipitation and removal of amine hydrochloride. However, this complex was typically generated in situ during early studies by the treatment of a combination of [lr(COD)Cl]2 and LI with an amine base, such as uPrNH2, l,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), or l,8-diazabicyclo[5.4.0] undec-7-ene (DBU). If a 1 1 ratio of iridium to ligand is used, a mixture of la and [Ir(COD)Cl]2 is produced. Helmchen et al. have reported that catalyst activation in the presence of tetrahydrothiophene (THT) prevents coordination of the k -phosphoramidite [71]. 

The basic poly(phenylene vinylene) (PPV) polymer is commonly prepared by the sufonium prepolymer route developed by WessUng and Zimmerman in 1968 but much modified by subsequent workers. The synthesis starts from 1,4-bis(chloromethyl)benzene, via the bis-sulfonium salt formed by reaction with tetrahydrothiophene, and then polymerisation is effected to give the prepolymer by reaction with lithium hydroxide (Figure 3.39). Because of the inherent insolubility of PPV it is this prepolymer that is used to form the film coating on the substrate, for example by using a doctor blade technique. The prepolymer is converted into PPV on the substrate by heating in an oven under vacuum at 200 °C for 8-10 h. 

An intramolecular cycloaddition reaction was also used in the synthesis of the annelated tetrahydrothiophene (97), starting from l,3-oxathiolan-5-one (96) (131) (Scheme 5.36). Thiocarbonyl ylide formation occurred by thermal extrusion of CO2 at 250 °C, yielding 97 in 62% yield. 

The enantiomeric synthesis of rranj-3,4-disubstituted tetrahydrothiophenes using a sulfur ylide cycloaddition has been reported <990L1667>. The sulfur ylide derived from the action of cesium fluoride on sulfide 111 underwent an asymmetric cycloaddition with chiral a,p-unsaturated camphorsultam amide 112 giving tetrahydrothiophene 113 (80% de). The configuration was confirmed by cleavage of the chiral auxiliary followed by reductive desulfurization with Raney-Ni which gave known carboxylic acid 114. 

The synthesis of quinolizidine (3-spiro-2 )-tetrahydrothiophene (67a, 67b), a model compound for the synthesis of dimeric sulfur alkaloids, was reported (65, 66). The compound was prepared from 2-cyanotetrahydrothiophene (66) by two independent routes, both utilizing phase-transfer catalysis (Scheme 10). 

Chiral bis(phosphinites) derived from (2/J,51 )-2,5-di(hydroxymethyl)tetrahydrothiophene have been prepared (Equation 73). These ligands have been used in the synthesis of rhodium complexes from Rh(COD)2X (COD = cyclooctadiene X = OTf, SbF6) and tested in the asymmetric hydrogenation of methyl a-acetamidocinna-mate. A maximum of 55% enantioselectivity was observed <19980M4976>. 

Symmetrical sulfides are obtained in 70-90% yields by refluxing aqueous alcoholic solutions of halides with sodium sulfide. The nonahydrate of sodiiun sulfide is a satisfactory reagent for the reac-tion. Tetramethylene and pentamethylene halides give cyclic sulfides, e.g., tetramethylene sulfide (tetrahydrothiophene) (64%). Halides containing several other important functional groups have been employed. Typical examples include methallyl chloride, and halides with hydroxyl, ethoxyl, carboxyl, and diethylamino groups in the beta position. A dry synthesis of phenyl sulfide from calcium oxide, sulfur, and chlorobenzene at 300° has been reported. ... 

Thietanes such as 13 are intermediates in the synthesis of thioctic acid.The formation of a five-membered tetrahydrothiophene derivative 16 as well as thietane 17 from 14 is explained by invoking an intermediate epoxide 15. A mixture of threo- and erythro-l,4-dichloro-3-pentanol (threoierythro, 1.6 1) gave similar results (45.4% 16, cis trans, 1.25 1 17.6% 17, threo erythro, 1.3 1). 

Extrusion of sulfur dioxide from the products resulting from the alkylation of tetrahydrothiophene 1,1-dioxides " and the 2-phenylthietane 1,1-dioxides, using n-butyllithium and lithium aluminum hydride - or photochemically leads to the synthesis of the corresponding cyclobutenes - and cyclopropanes, respectively (Scheme 107, entries a and b). 

Five membered ring sulfones (thiolene-1, 1-dioxides, sulfolenes or dihydrothiophene-1, 1-dioxides) can be obtained by peracid oxidation of tetrahydrothiophene. The extrusion of sulfure dioxide from dihydrothiophene-1,1 dioxides or sulfolenes like (178) has been much studied as it provides a synthetic route to dienes, e.g. butadiene (152) (Scheme 70). The reverse reaction provides a method of synthesis of sulfolene (178) from butadiene (152) and sulfur dioxide. Thiolene dioxides or sulfolenes can be generally prepared by addition of sulfur dioxide to conjugated dienes for example, 1,4-dimethylbutadiene (179) in the presence of sulfure dioxide, triethylamine and formic acid affords 2,5-dimethylsulfolene (180) (Scheme 71). 

Annulation /raw-3,4-Disubstituted tetrahydrothiophenes are obtained from conjugated carbonyl compounds and chloromethyl trimethylsilylmethyl sulfide in a reaction mediated by CsF. When the conjugated carbonyl component bears a chiral auxiliary, the process is amenable to synthesis of enantiopure derivatives. 

Dihydrothiophendioxide 122 adds CIF (generated from HF and A -chlorosuc-cinimide) giving tetrahydrothiophene-1,1-dioxide 123 used as a starting material for the synthesis of 3-chloro-4-fluorothiophene-1,1-dioxide 124. Compound 124 can be used in organic synthesis as fluorodiene. "... 

A few thiophene natural products have either been synthesized or recently isolated from plant sources. A short synthesis of the Otanthus Maritima amide 217 was recently disclosed . A group of known dithiophenes including 218 were isolated from Rhaponticum uniflorum . Finally, a novel tetrahydrothiophene, 6-hydroxythiobinupharidine (219), was isolated from a traditional Chinese medicinal plant, Nuphar pumilum . 

In 1982, chemists from Hoflfinann-La Roche published an elegant synthesis of biotin, in which, starting from cj tine, the tetrahydrothiophene ring is built up by an intramolecular [3 + 2]-cycloaddition of a nitrone. [129] The cyclisation occurs via a ten-membered ring system and generates two new stereogenic centres. 

The approach of Ogawa, Kawano and Matsui in Scheme 31 differs from that reported in Scheme 30 in the order in which the cyclic urea and tetrahydrothiophene rings were assembled. The latter, modeled after biosynthetic transformations, was formed in the final stages of the synthesis. 

Carbohydrates have again been used as chiral precursors for the total synthesis of other natural products, including thromboxane Bj, ( —)-isoavenaciolide, and insect pheromones - but pride of place must be given to a total synthesis of (-l-)-biotin from o-glucose in which a biomimetic transformation was used in forming the tetrahydrothiophen ring (Chapter 23). 

Tetrahydrothiophen-based nucleosides 10 have been produced from diacetone glucose in a multi-step synthesis, as outlined in Scheme 3. ... 

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