1,3-Diynes thiophenes

Di- and tetraynes with hydrogen sulfide in an alkaline medium at 20-80°C form systems containing linked thiophene cycles. Thus, l,4-dithienylbuta-l,3-diyne (47) forms 2,5-di(2-thienyl)thiophene (48) in 78% yield, whereas octa-2,4,6-tiiyn-l-ol (49) under the same conditions gives 5-hydroxymethyl-2-prop-1-ynylthiophene (50) in 50% yield (77HOU947). 

The reaction of hexa-2,4-diyn-l-al (64) with mercaptoacetaldehyde leads to 2-formyl-5-(prop-l-ynyl)thiophene (65). The addition direction is governed by the aldehyde group via intramolecular aldol condensation in the intermediate (77HOU947). 

The investigation of deprotonated hexa-2,4-diyne [KCH2C C=CCH3 H2C=C=C(K)C=CCH3] has shown (90DIS) that both carbanions are formed. In some cases CS2 reacts with the diyne carbanion to afford 2,5-disubstituted thiophenes 71 (90DIS). 

The condensed isobenzofuran derivative l,3-dimethyl-2,5,7-triphenyl-2/f-furo[3,4-/]isoindoloquinone (64), has been prepared in four steps from a pyrrole derivative143 (Scheme 79) a thiophene analog of64 has been obtained in a similar manner.144 Key intermediates in both types of reactions are condensed rhodacyclopentadienes (cf. 63) which are obtained from appropriate diynes. 

A novel route to 2,3-dihydrothiophenes involved a titanocene-promoted carbene formation and subsequenct intramolecular cyclization onto a thiol ester <99SL1029>. Treatment of thioacetal 9 with the low-valent titanium complex 10 gave 2,3-dihydrothiophene 12 by intramolecular olefination of the thiol ester of titanium-carbene intermediate 11. Another metal-mediated cyclization onto the thiophene ring system involved the palladium-catalyzed cyclization of 1,6-diynes <99T485>. For example, treatment of thioether 1,6-diyne 13 with Pdlj in the presence of CO and Oj in methanol followed by treatment with base gave 14. 

The most potent compound of the aryl diyne series (type II) was furan derivative 9 with a Ki value of 7.5 nM. An approximately tenfold decrease of potency was observed when the 1,3-substitution pattern of the head groups of 9 was replaced by 1,4-substitution to give 24 with a K, value of 80 nM. Substitution of the 2,5-furan ring in 9 by the 3,4-thiophene ring gave 25, with a twentyfold loss of tryptase inhibition activity (K, =150 nM). Replacement of the furanyl diyne template with the 1,3-substituted phenyl diyne template 29 was well tolerated (K, = 9 nM), whereas 1,4-substituted head groups resulted in a fourfold loss of activity (27, Ki = 32 nM) compared with 29. Combination of a 1,2-substituted phenyldiyne... 

Thieno[2,3-/)]thiophene (33) and the derivatives (33a-d) have been obtained in fair yields in a one-pot procedure using the substituted diynes (367) and carbon disulfide as building blocks (Scheme... 

Reaction of a four-carbon unit with sulfur sources such as hydrogen sulfide, carbon disulfide, and elemental sulfur is one of the traditional thiophene syntheses that belong to this category (Equation 18). A wide variety of hydrocarbons, for example, alkanes, alkenes, dienes, alkynes, and diynes, serve as four-carbon units. Another practical method is the sulfuration of 1,4-dicarbonyl compounds (Paal synthesis). The method has become very popular with development of sulfuration reagents such as Lawesson s reagent. The reaction of a,/3-unsaturated nitriles with elemental sulfur in basic media, Gewald synthesis, is also useful for the preparation of 2-aminothiophenes which are important compounds in dyestuff and pharmaceutical industries. 

The reaction of cw-Pt(dppp)Cl2 with terthiophene-diyne in the presence of 10 mol% Cul and 2-eq. of NEta at 25 °C gave (91 %) the stable iwplatinomacrocycle 38, which with iodine, followed by Na2S afforded the stable, red, microcrystalline octabutylcyclo[8]-thiophene in 19 % yield <03CC948>. 

Intramolecular bridging is also observed. For functionalized dienes (e.g., RCH=CHCOCH=CHR), ring closures occur with the formation of thiacyclohexanones, while the related bis alkenylketones result in the formation of the corresponding thiacyc-lohexadienones . Simple thiophene derivatives are formed by insertion of diynes into SCI2 . Similar chemistry is reported for Se halides, and tricyclo thia- and selena ethers are obtained from sequential addition of SCI2 and SeCb to cyclooctatetraene . 

Recent application of the nickel-catalyzed reaction with diyne 91 provides new effective access to functionalized silole derivatives 92, which are further utilized for the synthesis of silole-thiophene co-polymers (Eq.47) [84]. 

Much use has been made of conjugated diynes, which are also at the oxidation level of 1,4-dicarbonyl-compounds, which react smoothly with hydrosulhde or sulhde, under mild conditions, to give 3,4-unsubstituted thiophenes. Unsymmetrical 2,5-disubstituted thiophenes can be produced in this way too. ° Since nearly all naturally occurring thiophenes are found in plant genera, and co-occur with polyynes, this laboratory ring synthesis may be mechanistically related to their biosynthesis. 

A truly delightful exploitation of this idea is a synthesis of thieno[2,3- ]thiophene, in which a diyne is lithiated to give a lithio-allene, which reacts with carbon disulhde. ... 

Acetylene, as well as 1,3-diynes, also yield thiophenes with H2S under similar conditions ... 

Thiophene-cyclopentadienone cooligomers have been similarly prepared from an acetylenic precursor (Scheme 143) <94CC229>. The crucial step is the intramolecular cyclization of a diyne with 2,6-xylylisocyanide. 

Unsubstituted thieno[2,3-fi]thiophene was synthesized in satisfactory yield from trimethylsilylpenta-l,3-diyne (113) under very mild conditions. In this procedure, the reagents should be added in a reverse order -butyllithium is initially added to a suspension of Bu OK in dry THF at —100 °C followed by the addition of alkyne at —80°C, CS2 at —100°C and a solution of Bu OH in dry HMPA at —30°C (93BCJ2033). 

A one-pot procedure was developed for the synthesis of thieno[2,3-fi]thiophenes 114 using diynes 115 and CS2 as the building blocks (in 44-48% yields) (81MI1, 83CC1056, 91SC145). Allene derivative 116 was detected as an intermediate. 

The question of guest exchange in inclusion compounds received little attention, despite that fact that such processes are important for sensing and catalysis based on inclusion. However, a number of host-guest systems with organic and metal-containing hosts that entrap volatile guests were recently studied.The host l,l,6,6-tetraphenyl-2,4-diyne-1.6-diol H) forms inclusion compounds with tetrahydrofuran (THF), and thiophene (THIO), and we analyzed the dynamics of the reaction ... 

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