Tetrahydrothiophene derivative

Dichlorothiophene has become easily available through chlorination and dehydrochlorination of tetrahydrothiophened Another example of the aromatization of tetrahydrothiophene derivatives is the preparation of 3-substituted thiophenes by the reaction of 3-ketotetrahydrothiophene with Grignard reagents followed by the aromatization of the intermediate dihydrothiophene. Recent gas chromatographic analysis showed, however, that 2,3-dichlorothio-phene is the main product from the dehydrochlorination of tetra-chlorotetrahydrothiophene. 

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. 

It has been shown that Lewis acid catalyzed isomerization of thionolactones provides access to thiolactones. For example, exposure of the substrate 22 to catalytic amounts of BF3 OEt2 led to efficient conversion to the thiolactone 23. Such transformations were also found to give minor amounts of lactone or dithiolactone side products <06TL6067>. Substituted tetrahydrothiophene derivatives have also been obtained from 1,4-dithiane-2,5-diol and 2-nitroethyl acetate derivatives by a base induced sequence featuring a Michael addition and a Henry reaction <06TL8087>. 

Simply substituted thiocarbonyl ylides, including the parent system, react with activated olefins to form tetrahydrothiophene derivatives (30,31,52,53,131). Recently, the thermal desilylation method was applied toward the preparation of the Ceo-fullerene-fused tetrahydrothiophene 71 (132) (Scheme 5.26). 

The first diastereoselective synthesis of a tetrahydrothiophene derivative was reported by Karlsson and Hdgberg (32,95). The parent ylide la was added to a variety of C,C-dipolarophiles (79) bearing (—)-(15)-2,10-camphorsultam as the chiral auxiliary group to exclusively give trans-cycloadducts 80a,b with high diastereoselectivity [diastereomeric ratio (dr) 9 1], (Scheme 5.28). 

Alicyclic thioether sulfoxidation is also a route of biotransformation in bacteria and plants. For example, biotin (95), the most important naturally occurring tetrahydrothiophene derivative so far recognized, has been found to exist in bacteria as biotin sulfoxide (96)... 

Similarly, the epoxide (72), on reaction with BH3/UBH4, acetic acid or BC13 gave the tetrahydrothiophene derivatives (74a-c), presumably via the intermediate (73), unlike the analogous cyclohexyl and N-alkylpiperidyl compounds, in which the oxirane opened to give only the expected alcohols (equation 21) (75CPB2701). 

Photolysis of 8-thia-bicyclo[3.2.1]octan-3-one 115 in /butyl alcohol resulted in the formation of 4-but-3-enylthietan-2-one 116 in 19% yield and a tetrahydrothiophene derivative 117 in 5% yield accompanied by traces (4% and 3%) of exo- and . 

The side-arm alcohol plays a crucial role in controlling the reactivity and selectivity of the reaction. No reaction was observed if tetrahydrothiophene-derived sulfonium salts were used, or if the alcohol was protected as a methoxy group. The substrate is both activated and orientated by a hydrogen bond to its carbonyl group. No reaction intermediates were found in computational studies, so selectivity is determined in a single transition state. As before, controlling the ylide conformation and substrate approach determines the selectivity. The substrate approaches the ylide from the side bearing the alcohol in all cases, but 41a and 41b are predicted to present a different face of the ylide and so the opposite enantiomer is formed. 

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). 

A number of asymmetric cationic Au(II) complexes with a phosphine ligand have been synthesized starting from the symmetric triphenylphosphine or tetrahydrothiophene derivatives (Scheme 12)253,271. In solution, some of these products are in equilibrium with an equimolecular mixture of the corresponding symmetric derivatives. 

Electrochemical fluorination, widely used for preparation of perfluorinated terahydrofuranes can not be applied for the synthesis of tetrahydrothiophene derivatives due to oxidation of the sulfur. Electrochemical fluorination of tetrahydrothiophene and 2-methyltetrahydrothiophene resulted in low yield formation of the products 166 and 167, respectively. " ... 

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