Dihydrothiophenes, synthesis

A procedure for a synthesis of dienyl sulfoxides (232 and 233) involves ring opening of dihydrothiophene 1,1-dioxide (231) by two molar equivalents of Grignard reagent (equation 141)136. The yields are usually in the 20-66% range. Similarly, treatment of the bicyclic sulfones 234, with 2 equivalents of phenylmagnesium bromide, produced a mixture of 1,4-dienylic sulfoxides (equation 142)136. 

Dihydrodithiin sulphoxides, synthesis of 243 Dihydrothiophene dioxides, reactions of 653 /(,/( -Dihydroxyketones 619 Dimerization, photochemical 877, 884 Dimethyl sulphoxide anion of - see Dimsyl anion hydrogen bonding with alcohols and phenols 546-552 oxidation of 981, 988 photolysis of 873, 874, 988 radiolysis of 890-909, 1054, 1055 self-association of 544-546 Dimsyl anion... 

The synthesis of substituted 3,4-dihydrothiopyrans by the reaction of 2-amino-4,5-dihydrothiophene-3-carbonitriles with ethyl diazoacetoacetate involves rearrangement of initially formed 1,4-oxathiocines <96LA725>. 

The synthesis of N-phenyl-1,3,4,6-tetrahydrothieno(3,4-c)-pyrrole-2,2-dioxide (II) was carried out by reacting aniline with 3,4-bis(bromomethyl)-2,5-dihydrothiophene-l,1-dioxide (I). The latter compound was synthesized by the bromination of the cycloaddition product, prepared from 2,3-dimethyl-l,3-butadiene and sulfur dioxide (17). 

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],... 

Additional studies featuring reactions of thiophene derivatives detail biohydrolysis of (S)-3-(thiophen-2-ylthio)butanenitrile <06TL8119>, lipase catalyzed resolution of thiotetronic acids <06TL7163>, enzymatic kinetic resolution of l,l-dioxo-2,3-dihydrothiophen-3-ol <06TL5273>, and efficient synthesis of 6-methyl-2,3-dihydrothieno[2,3-c]furan 55, a coffee... 

Synthesis of the dihydrothiophene derivatives was described by Flynn et al. [70] (depicted in Scheme 23) and involved the conversion of 3-butynol 92 to benzyl 3-butynal sulfide 93. Sonogashira coupling of the sulfide 93 with acetic acid 5-iodo-2-methoxyphenyl ester 94, produced the intermediate 95. Treatment of compound 95 with iodine resulted in a rapid and... 

The synthesis of dithienylethenes bound to heteroanalogs of cyclopentene, in particular to the 2,5-dihydrothiophene ring, also deserves notice. Diketone 135 was prepared by the replacement of the bromine atoms in two molecules of 134 by the sulfide anion followed by the McMurry cyclization to form thiacyclopentene derivative 136 (03OL1435). Diiodide 137 is also successfully used as the synthon for the subsequent functionalization this compound is involved in the Suzuki reaction to... 

Diels-Alder route to cantharidin. Use of high pressure to facilitate. Diels-Alder reactions has led to a simple synthesis of cantharidin.1 The obvious dienophile component, dimethylmaleic anhydride, is unreactive to furane even under high pressure, but 2,5-dihydrothiophene-3,4-dicarboxylic anhydride (l)2 reacts with furane at 25° under 15 kbar of pressure to give the exo-adduct (2) and the endo-isomer as a 85 15 mixture. The major adduct is converted into cantharidin (3) by reduction and desulfurization over Raney nickel in 63% overall yield. 

BASF chemists2 report that this reaction is highly effective for dehydrogenation of both 2,5- and 4,5-dihydrothiophenes. It was examined in the course of a synthesis of an artificial sweetener thiophcnesaccharin (4), which is 1000 times sweeter than sucrose and which lacks a bitter aftertaste. The commercial synthesis of 4 from 3 includes this dehydrogenation as one step. 

An approach to the synthesis of angularly substituted polycyclics through the Diels-Alder cycloaddition of dihydrothiophenes has been devised (69JA7780). The easily prepared 2,5-dihydro-4-methoxycarbonyl-2-thiopheneacetic acid methyl ester (316) was heated at 180 °C with excess butadiene to yield (317). Desulfurization and double bond reduction of the cycloadduct with W-5 Raney nickel gave (318) which was characterized by conversion to the corresponding diacid and comparison with an authentic sample. Dieckmann cyclization of (318) is known to lead to the 5-methyl-1-hydrindanone (319 Scheme 68). The use of other dienes in the [4 + 2] cycloaddition process will, of course, produce more highly functionalized hydrindanones. 

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. 

Thioselenoesters synthesis of 44 Transthioacetalization 16 2-Tributylstannyl-2,5-dihydrothiophene-S,S-dioxide 177... 

An attempted synthesis of dithioesters 220 by stepwise treatment of enolates from cyclopropanes 97 with carbon disulfide and methyl iodide lead to an unexpected new product without a cyclopropane ring. By spectroscopic means and study of the reactions dihydrothiophene structure 222 has been established 98). 

The synthesis and properties of dihydrothiophenes have been reviewed by Shvekhgeimer <1998CHE1101>. 

Although conversions of tetrahydrothiophenes (thiolanes), dihydrothiophenes (sulfolenes), thiophenones, and related compounds to the corresponding thiophenes do not involve a process of ring transformation, they are important in the synthesis of thiophenes. 

This methodology was further studied for the total synthesis of the Elaeokarpus alkaloids elaeokanine A (123) and B (122) (80JOC3372 81JA6387). This monoene moiety was prepared in masked form via amide dihydrothiophene dioxide. After O-silylation of methylol acetate 120, the... 

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