Thiophene transition-metal-catalyzed cross-coupling

Much work has been directed towards the synthesis of thiophene oligomers and polymers. This is due to the current interest in research on conducting polymers and molecular electronics (92CRV711). Two main approaches have been used for making such polymers (i) chemical (e.g. FeCl3) or electrochemical oxidation of monomeric thiophenes and (ii) transition metal-catalyzed cross-coupling reactions. 

Transition metal-catalyzed cross-coupling reactions of thiophenes have been extensively covered in CHEC-II(1996). These include ... 

The introduction of a polyfluorinated chain is not so easy as that of an alkyl chain. Transition metal catalyzed cross-coupling of Grignard reagents and organozinc compounds are inefficient in the synthesis of polyfluorinated 3-alkylthiophene. The copper-catalyzed perfluoroalkylation results in the formation of 2-and 3-substituted thiophenes, which are difficult to separate from each other. The reaction of fluorinated alkylmagnesium iodide with 3-formylthiophene, follwed by reduction with lithium aluminum hydride, gave (22) in an overall yield of 40% [27]. 

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. 

Heteroaryl phosphonates are common motifs in biological compounds and have stimulated the development of transition metal-catalyzed methodologies for C-P bond formation [68]. Phosphonated thiophenes 43 are accessible via silver-catalyzed dehydrogenative cross-coupling of thiophene 1 with dialkyl phosphites 42 (Scheme 19) [69]. The reaction is performed in aqueous dichloromethane, proceeds regioselectively at the a-position, and utilizes silver(l) nitrate as catalyst and the oxidant potassium persulfate. 

DeBoef demonstrated the utility of the C2-selective oxidative cross-coupling of indole and benzene previously reported by his group in the expedient synthesis of a botulinum neurotoxin inhibitor (Scheme 10) [53]. The streamlined synthesis featured an oxidative cross-coupling of methyl-AT-SEM-indole-6-carboxylate with benzene, and after further elaboration, a direct arylation of a thiophene moiety that had been incorporated into the molecule. This formal synthesis highlights the efficiency of transition metal catalyzed reactions at C-H bonds in the planning of synthetic routes. 

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