Metallation of thienothiophenes

It was also shown, by Challenger and Gibson, that the carboxylic acids formed on oxidation of 2-acetylthieno[2,3-6]thiophene and on metalation of thienothiophene 1 followed by carbonation, were identical. 

The assignment of the orientation in the bromo derivative (82) was confirmed by transformation via halogen-lithium exchange and carbonation to the known acid (55 Scheme 25). The orientation of bromine in (83) was proved by an independent synthesis via direct metalation of thienothiophene (3) followed by treatment with bromine (Scheme 26). Both bromo derivatives (82) and (83) were stable at -15°C or in acetone solution for several days whereas at 20 °C they decomposed within a few hours. 

The above reactions exemplify the wide range of applications of metallation of thienothiophenes, which allows one to prepare new derivatives of this class of heterocycles, including those having useful properties. 

Syntheses of unsubstituted thieno[3,2-A]thiophene (2) and 3-methyl-thieno[3,2-6]thiophene were carried out in a similar way metalation of 3-bromothiophene with n-butyllithium at —70° and subsequent treatment with sulfur and methyl monochloroacetate gave methyl (3-thienyl-thio)acetate (60). Further reactions along the lines indicated above led to the thienothiophenes 2 and 27. 

Carbonation of monolithio-thienothiophenes 1 and 2 formed by metalation with one equivalent of n-butyllithium fiimished the 2-carboxylic acids in good yields. Two equivalents of n-butyllithium led to the 2,5-dicarboxylic acids. Metalation of the thienothiophene system at a d-position was not observed. 

For competitive metalation of thiophene and the isomeric thienothiophenes 1 and 2, see Section IV,A and Table VII. 

Metalation of thieno[3,4-6]thiophene (3) with one equivalent of n-butyllithium at —20° followed by dimethylformamide produced a mixture of 4-formyl (194) and 6-formylthieno[3,4-b]thiophene (195) in a 1 4 ratio, in contrast to the 7 3 ratio obtained by Ae Vilsmder formyla-tion of thienothiophene 3. ... 

Addition of carbon disulfide to the carbanion, generated from the allene (13), and intramolecular addition of the dithiocarboxylate sulfur to the triple bond gives the compoimd (14) (Scheme 5) <85TL5I31>. Metallation of the diynes (15), followed by the successive addition of carbon disulfide, Bu OH, and HMPT, affords thienothiophenes (17) in reasonable yields (Scheme 6), and the use of the sulfides (18) as the starting material produces the thienodithiins (19) (Equation (3)) when R is TMS in the starting compounds, the unsubstituted parent compounds are obtainable in these cases since desilylation probably takes place at some intermediate stage <83CC1056>. 

Bromine derivatives of thiophene are the most widely used for the preparation of isomeric thienothiophenes and related systems. A classical example is illustrated by the following transformation sequence formylation of 3,4-dibromothiophene (1) through lithium derivatives, repeated metallation and treatment with elemental sulfur and methyl bromoacetate. Ring closure of the second heterocycle occurs in the present of sodium alkoxide. Decarboxylation of the resulting 4-bromothieno[2,3-Z ]thiophene-2-carboxylic acid (2a) affords 3-bromothieno[2,3-Z)]thiophene (3a) (74IZV1570). The reaction with selenium instead of sulfur produced 4-bromosele-nolo[2,3-Z ]thiophene-2-carboxylic acid (2b) and 4-bromoselenolo[2,3-Z)]thiophene (3b). 

Isomeric thienothiophenes and their derivatives are of considerable interest as electron donors or acceptors for the design of new types of charge-transfer complexes and as ligands coordinating metal ions. As mentioned above (see Section IV.D), charge-transfer complexes of some five-membered fused heteroaromatic systems with TCNE were studied by UV and IR spectroscopy and their relative stabilities were discussed using the association constants and enthalpies of formation (82CS214). 

L. S. Fuller, B. Iddon and K. A. Smith, Thienothiophenes. 2. Synthesis, metallation and bromine—>lithium exchange reactions of thieno[3,2-i>]thiophene and its polybromo derivatives, /. Chem. Soc., Perkin Trans. 1, 3465-3470 (1997). 

The thienothiophens, like thiophen, are smoothly metalated by ethereal butyl-lithium in the a-positions. By means of competitive metalation experiments, both thieno[2,3-Z>]thiophen and thieno[3,2-Z>]thiophen were found to be about six times more reactive. The unsymmetrical thieno-thiophen (296) gives the 4-lithio- and 2-lithio-derivatives in a 1 4 ratio. Also, (293) and (294) are smoothly metalated in the a-positions. Halogen-metal exchange between 2,3,5-tribromothieno[3,2-6]thiophen and butyl-lithium at — 70 °C followed by hydrolysis could be used for the synthesis of the 2,6-dibromo-compound. However, the same reaction with 2,3,5-tribromothieno[2,3-6]thiophen led to ring-opening. 

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