Tetra-hydrothiophens

Di- and Tetra-hydrothiophens. - Direction control in the preparation of the very useful 3-oxotetrahydrothiophens has been achieved by using half-thiol 

522 605, 1981 Otkrytiya, Izobret, Prom. Obraztsy, Tovamye Znaki, 1981, 286). 

Malkhasyan, E. M. Asatryan, S. M. Mirakyan, and G. T. Martirosyan, USSR P. 810 696, 1981 (Otkrytiya, Izobret, Prom. Obraztsy, Tovamye Znaki, 1981, 92). 

Sulphur analogues of prostaglandins that contain di- and tetra-hydrothio-phen rings, such as the sulphur analogue of A -PGIi and (52)- and (5 )-6,9-thiaprostacycline, have been described. A series of methylated derivatives of 2-thiobiotin has been synthesized and their i.r. and their and n.m.r. spectra have been investigated. Other aspects of di- and tetrahydrothiophens are discussed in refs. 347 - 350. 

Di- and Tetra-hydrothiophens.—Birch reduction of thiophen-2-carboxylic acid with three equivalents of lithium in liquid ammonia gave 2,5-dihydrothiophen-2-carboxylic acid and several other products. When the Birch reduction was carried out with five equivalents of lithium and with methanol as the proton source, a single product, c/s-5-mercaptopent-3-enoic acid, was obtained. Birch reduction of t-butyl 5-t-butylthiophen-2-carboxylate gave the 2,5-dihydro-derivative upon treatment with zinc dust and trimethylchlorosilane and then quenching with molar sodium hydroxide, this gave a mixture of (123) and (124) in the proportions 1 8.  

An unusually facile Pummerer rearrangement was observed in the conversion of 4-hydroxy-3-(l-alkylsulphinyl)sulpholans into 4-acetoxy-3-(l-alkylthio)-2- 

The base-catalysed isomerization of /3-epoxy-sulphones (126) to y-hydroxy-ajS-unsaturated sulphones (127) was shown by kinetic data, an isotope effect, and stereochemistry to involve an intramolecular suprafacial 1 - 3 hydrogen migration, with a carbanion-like transition state. 4-Hydroxy-2-sulpholen, 3-hydroxy-4-chlorosulpholan, and 3,4-epoxysulpholan were found to react with thiolates to give mixtures of cis- and tran5-3-hydroxy-4-(alkylthio)sulpholans in a ratio of 2 3.  

Polakova, M. Palecek, and M. Prochazka, Collect. Czech. Chem. Commun., 1979, 44, 3705. 

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A 100-mL round-bottomed flask containing a Teflon-coated magnetic stirring bar is charged with a solution of 0.45 g (1 mmol) of (pentafluorophenyl)(tetra-hydrothiophene)gold(I) in 50 m L of diethyl ether, to which is added, 0.15 mL (1 mmol) of pdma. After stirring for 5 min at room temperature formation of a white precipitate is observed. Concentration of the solvent to 10 mL causes white crystals to precipitate, which are filtered, washed with two lOmL portions of hexane, and dried. Yield 0.52 g (80%). 

The parent thiocarbonyl ylide (39), generated by cesium fluoride-induced desilylation of (38), is trapped with alkenes bearing electron-withdrawing substituents and with DMAD to give tetra-hydrothiophenes (40) (58-86%) and dihydrothiophene (41) (56%), respectively (86CC1073). With alkenes the original stereochemistry of the alkenes is retained. 

Dihydrothiophene derivatives have been utilized for the synthesis of both tetra-hydrothiophenes and thiophenes. One of the syntheses of biotin has made extensive use of substituted 2,5-dihydrothiophenes (77JOC1630) stereospecific catalytic reduction to the tetrahydro level was reserved until a late stage (Scheme 213). The stability of the intermediate 2,5-dihydrothiophenes was ensured by proper choice of substituents at the 3- and 4-positions. 

R = 2-ketocyclopentyl), which is the sole product of oxidation using di-t-butyl peroxide.323 Similarly di-t-butyl peroxide-catalysed free-radical addition of tetra-hydrothiophen to /2-pinene yields (225 R = tetrahydrothiophen-2-yl),324 as expected from the previously reported diethyl phosphite addition (Vol. 5, p. 40). ... 

Ultraviolet (UV) irradiation of chiral thiol 95 in the presence of 2,2 -azobisisobutyronitrile (AIBN) gives tetra-hydrothiophene 96 without epimerization <20000L3757>. 

In our preliminary report on the use of MMPP we showed that tetra-hydrothiophene could be oxidised selectively to afford either the sulfoxide or the sulfone [5], and using UHP at room temperature we were only able to isolate the sulfone [11]. Careful control of the amount of MMPP used has allowed the preparation of sulfoxides as shown in Eqs. (39 and 40) [47], while use of an excess of MMPP allows sulfones (Eqs. 41 and 42) to be isolated in good yields [48,49]. 

The reactivity of tetrahydrothiophene (thiolane), tetrahydrothiophene-1-oxide and tetra-hydrothiophene-1,1-dioxide (sulfolane) have been discussed in detail in CHEC-I <84CHEC-I(4)741>. The present review will therefore deal only with the more recent results in this area. 

Reaction of readily available thiazolidinones (487) with NBS affords 3,4-disubstituted tetra-hydrothiophenes (488) (Equation (97)) <87CC1577>. No explanation for the mechanistic pathway of this reaction was given except that it might involve the initial electrophilic attack of NBS on the sulfur atom. 

FIGURE 5.3 This copolymer was prepared from a precursor in which the tetra-hydrothiophene units employed by Wessling were replaced by ethybcanthates. When heated, not all of the xanthate groups were eliminated and both cis and trans linkages were formed, as opposed to the all trans PPV prepared by Wessling. Incorporation of cis linkages prevented crystallization and enhanced PL and EL efficiencies. 

Solvents in which an oxygen donor atom has been replaced by a sulfur atom switch from hard to soft solvents. Tetrahydrofuran can thus be compared with tetra-hydrothiophene n = 0.00 and 0.80, respectively. Some other such solvent pairs are 7V,7V-dimethyl-thioformamide ( =1.35) compared to DMF (jU=0.11), N-methyl-thiopyrrolidinone (/<=1.35) compared to NMPy (/t = 0.13), diethylsulfide (fx=0.68) compared to diethylether ( /=0.00), and hexamethyl thiophosporamide (fi = 1.57) compared to HMPT fi=0.29). Solvents with nitrogen and phosphorus donor atoms are also soft, for example, pyrrole (/i=0.81) and aniline ( =0.75) [3]. 

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