Metallation of thiophenes

A primary isotope effect /ch/ d of 6.4 (extrapolated for 35 C) is observed for the metalation and the methylation of 171b when the C-5 position is deuterated. This value is in excellent agreement with the primary isotope effect of 6.6 reported for the metalation of thiophene (392) and it confirms that the rate-determining step is the abstraction by the base of the acidic proton. 

Metalation of Thiophenes with Organolithium Compounds (Nucleophilic Substitution on Hydrogen)... 

The metalation of thiophene with n-butyllithium, discovered by Gilman et gives rapidly 2-thienyllithium in almost quantitative... 

Competitive metalation of thiophene and 2-methylthiothiophene with a deficiency of n-butyllithium gave only 2-methylthio-5-thio-phenecarboxylic acid, showing the activating effect of the methylthio group. ... 

To summarize, electrophilic substitutions and metalations of thiophenes take place preferably at the a-positions due to the electronegativity of the sulfur atom. This is the consequence of the more effective incorporation of lone pair electrons on the sulfur into the aromatic system. Although regioselective reactions are routinely performed for oc,p-dihalofurans, regioselectivity is not as easily achieved in Pd-mediated chemistry with oc,p-dihalothiophenes. 

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

Butyllithium in hexanes (2.5 M) is purchased from the Aldrich Chemical Company, Inc. and titrated with 2-pentanol in ether, using 1,10-phenanthroline as indicator before use.2 Use of lower concentrations of butyllithium for the metalation of thiophene under these conditions results in incomplete lithiation. 

Clarke, A. J. McNamara, S. Meth-Cohn, O. Novel aspects of the metalation of heterocycles. Side-chain metalation of thiophene and ring metalation of six-membered nitrogen heterocycles. Tetrahedron Lett. 1974, 2373-2376. 

The yield cited is that of the carboxylic acid from metalation of thiophene or 3-methyltbiophene. 1 Average yield of six runs. 

Metallation of thiophene 2- and 3-esters takes place adjacent to the ester functionality, i.e. at C-3 and C-2, respectively. ... 

Organometallic Derivatives of Monocyclic Thiophens - Lithium. Numerous a-substituted thiophens have been prepared via metallation of thiophens with organolithium derivatives. Thus 2-thienyl-lithium has been allowed to react with tetraisopropylthiuram disulphide to give 5-(2-thienyl) A(,A -di-isopropyl-dithiocarbamate in quantitative yield. ° Through the reaction of 2-thienyl-lithium with tellurium in THF, the tellurolate was obtained, which was converted into various products. The reaction of 2-thienyl-lithium with 1,1-dichloro-2,2-difluoroethene has been developed into a very useful method for... 

Synthesis with addition of 1 C-atom Metalation of thiophenes... 

Although the metallation of thiophene with butyllithium in a THF-hexane mixture proceeds much more easily, ethyllithium in Et20 (prepared from ethyl bromide and lithium) is chosen as the lithiation reagent for the following reasons. 2-Methylthiophene has a boiling point of 112.5 °C, and a distillative separation from the THF and hexane (b.p. between 65 and 70°) would therefore be more difficult and lengthy. Moreover, traces of butanol could be present in the... 

Metalation and Halogen-Metal Exchange.—The direct metalation of thiophens with organolithium compounds and the halogen-metal exchange reaction between halogenothiophens and organolithium derivatives have... 

Miscellaneous Fused Selenophens.—Selenolo[2,3-6]thiophen (691) has been prepared by metalation of thiophen>3-aldehyde diethyl acetal with butyl-lithium followed by reaction with selenium and methyl chloroacetoacetate. The intermediate (692) was, without isolation, hydrolysed and ring-closed to (693), which upon decarboxylation gave (691). Another isomeric... 

Abstract This chapter reviews the metallation of thiophenes, the utilization of the resulting organometal species as nucleophiles and as cross-coupling partners, and the cross-coupling reactimis of halothiophenes and thiophenes. The main focus lies on transition metal-catalyzed carbon-carbon bond formations. 

The most conunon organoUthium reagent for the metallation of thiophene is BuLi or BuLi/TMEDA, respectively. Alternative applicable reagents are lithium metal/naph-thalene [7], alkyllithium/amine complexes [8], or lithiated polystyrene [9]. In the case... 

Scheme 5 Metallation of thiophenes followed by formylation with N-formylpiperidine [27]...

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