Thieno-thiophenes lithiation

Compound 145 on lithiation <1999SM(102)987> and subsequent reaction with carbon dioxide afforded compound 146. Sandmeyer reaction of 2-bromodi thieno[3,2-A2, 3 -with copper(l)cyanide in hot iV-methyl pyrrolidine (NMP) gave the corresponding nitrile 148 which was then converted to the tetrazole 149 with a mixture of sodium azide and ammonium chloride in NMP in low overall yield (Scheme 14) <2001JMC1625>. 

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. ... 

The use of thienyl Grignard reagents, and more recently lithiated thiophenes, has been extensive and can be illustrated by citing formation of oxythiophenes, either by reaction of the former with f-butyl perbenzoate or the latter directly with bis(trimethylsilyl) peroxide or via the boronic acid, the synthesis of thiophene carboxylic acids by reaction of the organometallic with carbon dioxide, the synthesis of ketones, by reaction with a nitrile, or alcohols by reaction with aldehydes, by the reaction of 2-lithiothiophene with A -tosylaziridine, and by syntheses of thieno[3,2- ]thiophene and of dithieno[3,2- 2, 3 - /]thiophene. Some of these are illustrated below. 

Thieno[3,4- ]thiophene was prepared from 3,4-dibromothiophene utilising the two halogens in separate steps palladium-catalysed coupling and lithiation by... 

Lithiation of thieno[3,2- )]thiophenes 145a, b gives 2-lithium derivatives, whose treatment with chalcogens and iodomethane affords chalcogenides 159 (96JCS(P2)1377). Vilsmeier-Haack formylation of the latter produces aldehydes 160, whereas the reaction with tetracyanoethylene (TCNE) in DMF affords 5-tricyanovinyl derivatives 161. 

Tetrathiabenzo[l,3-cfirst time by dimerization of thieno[2,3- >]thiophene (142) (92PS73). More recently, it was found that catalytic reduction of 3,4-dibromothieno[2,3-i]thiophene (227) with an excess of activated zinc in the presence of bis(triphenyl-phosphine)nickel(II) chloride and tetraethylammonium iodide afforded only 4,4 -dibromo-3,3-bis(thieno[2,3- )]thiophene) (228) (in a maximum yield of 28%) (89AG1254). However, the reaction in the presence of a larger amount of the nickel catalyst afforded also dipenatlene 225. Optimization of the reaction conditions made it possible to increase the yield of the latter to only 14%. An alternative procedure was employed to transform thienothiophene 227 into trimethylstannyl derivative 229. The reaction of thienothiophene 227 with organotin intermediate 229 in the presence of the palladium triphenylphosphine complex afforded dipentalene 225 (13% yield). Derivatives 226 were prepared by lithiation of... 

The synthesis of thieno[3,2- >]thiophene [17, 18] is shown in Scheme 3.3. The commercially available 3-bromothiophene undergoes formylation via lithiation at the 2-position and the addition of Al-formy[piperidine. Subsequent treatment of 3 with ethyl 2-sulfanylacetate affords the ester 4, which is converted to thieno[3,2- >]thiophene by hydrolysis and decarboxylation steps. The product is thus obtained in a very satisfactory overall yield of 60%. A similar method can be used to prepare thieno[2,3- >]thiophene from thiophene-3-carboxaldehyde via the carboxylic acid [19], but an attractive alternative route was published in full by Otsubo et al. [20] following a brief communication from de Jong and Brandsma [21], In this strategy, trimethylsilyl-l,3-pentadiyne is treated with potassium rerr-butoxide, butyllithium and carbon disulfide and then with ferr-butanol in HMPA, to obtain thieno[2,3-fi]thiophene in 46 % yield. The reaction sequence can be used to obtain the product in multigram quantities and the diacetylene derivative can be easily prepared from (Z)-l-methoxybuten-3-yne in 65 % yield. 

The preparation of thieno[3,2-fc]thiophene was reported by Iddon and co-workers [76, 77] and it is readily prepared in four steps from commercially available 3-bromothiophene (Scheme 17.1). Thus 3-bromo-thiophene can be lithiated in the 2-position with a bulky non-nucleophilic base such as lithium diisopropylamine. Quenching of the resulting thiophene anion with dimethylfonnamide or tV-formylpiperidine afforded the thiophene aldehyde. Treatment of this o-bromoaldehyde with ethyl 2-sulfanylacetate in the presence of base afforded thieno[3,2-fc]thiophene carboxylate ester in good yield. Hydrolysis of the ester group, followed by thermal decarboxylation of the resulting acid with quinoline in the presence of copper, afforded the unsubstituted thieno[3,2-f>]thiophene in overall yields of approximately 60 % over the four steps. 

Three thieno[3,4-h]thiophene dimers, namely 2,2 -bis-(thieno[3,4-b]thiophene) (163), 4,4 -bis(thieno[3,4-h]thiophene) (160), and 6,6 -bis(thieno[3,4-b]thiophene) (157), were synthesized using CuCl2-promoted coupling (Scheme 36) [59]. Note the subtle use of regioselective lithiation, lithiation then blocking and lithiation and double blocking, to reach 157,160, and 163 respectively. 

Lithiation of thieno[2,3-h]thiophene (3) followed by treatment with A, A -dimethylformamide gives the dialdehyde 210, which on reaction with Wittig-reagents (211 and 212) produces heterohelicenes 213 and 214, respectively... 

Reactions.—All the mono- and poly-bromo-derivatives, as well as iodo-derivatives, of thieno[2,3-h]thiophen have been prepared by direct bromination or iodination, or from the lithium compounds, and characterized by their n.m.r. spectra. Boronic acids were obtained from several alkyl- and aryl-thienothiophens via lithiation and were converted by hydrogen peroxide oxidation into the tautomeric hydroxy-derivatives. It was shown by n.m.r. that all thieno[2,3-h]-thiophen systems exist as thieno[2,3-h]thiophen-2(3 )-ones, while in the case of... 

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