2- Iodothiophene, reaction with

Nucleophilic Reactions. Useful nucleophilic substitutions of halothiophenes are readily achieved in copper-mediated reactions. Of particular note is the ready conversion of 3-bromoderivatives to the corresponding 3-chloroderivatives with copper(I)chloride in hot /V, /V- dim ethyl form am i de (26). High yields of alkoxythiophenes are obtained from bromo- and iodothiophenes on reaction with sodium alkoxide in the appropriate alcohol, and catalyzed by copper(II) oxide, a trace of potassium iodide, and in more recent years a phase-transfer catalyst (27). 

Procedures have been worked out which increased the yield of 2-bromothiophene to 78% on direct bromination in acetic acid-ether mixtures and to 67% in carbon tetraehlorided With the mild brominating agent, dioxane dibromide, quantitative yields of 2-bromothiophene are obtained. A very convenient procedure for the iodination of thiophenes consists of the acid-catalyzed (HzSOi) reaction with iodine and HIO3, giving 2-iodothiophene in 75% yieldd In contrast to the HgO method, all the iodine is utilized. 

We continued our work with the reductive Heck and Domino-Heck reactions [1, 7J of new bicyclic compound (3) by treating it with different aryl- and hetaryl-iodides, as a result a series of new epibatidine analogues were synthesized, continuously separated and purificated by column chromatography on silica gel. Treatment of 3 with iodobenzene, 2-iodothiophene, 1-iodonapthalene and 2-chloro-5-iodopy-ridine under reductive Heck conditions gave new compounds 4a-d and 5b, 5d as exo-regioisomers after chromatographic separations. The reactions with iodobenzene and 1-iodonapthalene gave only 5-exo- products. The use of trimethylsily-lacetylene under Domino-Heck conditions provided alkynic bicyclic systems 6e andf. 

The photochemical coupling between methyl 5-iodothiophene-2-car-boxylate (119) and 2-chlorothiophene gave the corresponding bithiophene 140. Also, in this case the reaction with propyne gave a naturally occurring bithiophene 142 isolated from Arctium lappa (89JPP(A)(47)191). 

Halofuran and halothiophene derivatives undergo photochemical reactions with arylalkenes and arylalkynes and with benzo[6]furan513,514. With the arylalkenes and aryl-alkynes, heteroarylation takes place at the terminal alkene or alkyne carbon atom, while benzo[6]furan is substituted at position 2. The experimental results are interpreted in terms of solvent-separated or contact radical ion pairs. Iodothiophene and iodofuran derivatives can also be used to synthesize derivatives of benzimidazole by means of photochemical coupling515. The reaction of 5-iodothiophene-2-carboxaldehyde (157) with benzimidazole (158) giving the coupling product 159 is illustrated in equation 131. 

Thienylzincates are available using lithium di-zW-butyltetramethylpiperidinozincate (TMP-zincate) <1999JA3539> thus, ethyl thiophene-3-carboxylate is easily metallated at C(2) at room temperature, subsequent reaction with iodine giving ethyl 2-iodothiophene-3-carboxylate in 89% yield. Similarly ethyl thiophene-2-carboxylate gives the 5-iodo derivative in 62% yield. 

Treatment of 2-iodothiophene 830 with Z molar equiv of diethyl acetylenedicarboxylate in the presence of Pd catalyst affords tetrasubstituted benzothiophene 834. d y -addition of intermediate 831, generated by oxidative addition of 830 to Pd(0), to the acetylene gives vinylpalladium 832. Cyclization of 832 to 833 and its subsequent reaction with the acetylene affords the final product 834 (Scheme 126) <2003JOC6836>. Intramolecular electro-cyclization of the intermediate 837, produced by the reaction of the propargyl methyl carbonate 835 with 2-thiophene boric acid 836 in the presense of Pd catalyst, affords benzothiophene 838 (Scheme 127) <2004CEJ5338>. 

Grigaard reaction. The Grignard reagent from 2-iodothiophene reacts with sulfur to form a derivative suitable for methylation. ... 

Addition of iodine to a solution of 3-lithiothiophene in THF gave the expected 3-iodothiophene in a moderate yield together with two isomeric di-iodo compounds. We presume that 3-lithiothiophene lithiates 3-iodothiophene at the 2- and 5-positions respectively further reaction with iodine gives the di-iodo compounds. These yield-reducing side reactions could be suppressed completely by conversion of 3-lithiothiophene into the less reactive Grignard compound by addition of MgBr2. 

The photolysis of iodothiophene to generate thienylradical and subsequent reaction with benzene... 

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