P. Hu, Min Zhang, Xiaoming Jie
Jan 2, 2012
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170
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Angewandte Chemie
Abstract
Conventionally, 2-arylthiophenes are synthesized by cross-coupling reactions of (hetero)aryl halides with (hetero)aryl organometallic reagents. Owing to the wide applications of this family of compounds, the development of new methods for the synthesis of valuable 2-arylthiophenes from simple and readily available starting materials by concise steps continues to be a target of intense interest. In this context, the direct C H arylation of thiophenes with aryl iodides and bromides has been achieved by using Pd, Ir, Rh, and Cu catalysts; thus thiophenes were directly used to replace expensive thienyl organometallic reagents in traditional cross-coupling reactions. As a highly efficient approach to 2-arylthiophenes, the oxidative cross-coupling of two unfunctionalized arenes has been realized in the palladium-catalyzed reactions of thiophenes with C H acidic polyfluoroarenes and nitrogen-containing heteroarenes. Moreover, metal-free oxidative cross-couplings of thiophenes with electron-rich arenes has also been reported. Although these transformations represent substantial progress toward the syntheses of 2-arylthiophenes in an atom-economical and environmentally benign way, there is significant room for improvement with respect to the generality and functionalgroup tolerance of these state-of-the-art methods. On the other hand, the use of carboxylic acids as crosscoupling components by a metal-promoted decarboxylation process is a rapidly growing area of research because of their low cost, diversity, and ready availability. Recently, decarboxylative cross-coupling reactions have been expanded to decarboxylative C H bond functionalization, including intramolecular reactions for the syntheses of dibenzofurans, intermolecular reactions for the selective arylation of indoles, ortho acylation of acetanilides, the construction of azole–azole linkages, and the direct arylation of C H acidic polyfluorobenzenes. A decarboxylative C H bond functionalization that combines two newly emerging approaches, that is, decarboxylation and direct C H bond functionalization, offers a new synthetic strategy in synthesis. However, the challenges posed by this promising process remain. For example, many of the decarboxylative C H bond functionalization reactions were restricted to a narrow range of arene carboxylic acids because the reactivity of the arene carboxylic acids toward decarboxylation is very sensitive to the substitutents on benzene rings. Herein, we report the decarboxylative C H bond arylation of thiophenes catalyzed by a Pd(OAc)2/Ag2CO3 system; electron-rich, electron-deficient, and heterocyclic benzoic acids can all be used as aryl sources in this reaction and a broad spectrum of functional groups can be tolerated. As generally proposed for similar processes, the Pd/Agcatalyzed decarboxylative C H arylation of thiophenes may involve a Pd-promoted C H cleavage to form a palladium intermediate, a Ag-promoted decarboxylation to generate an aryl silver species, a subsequent aryl transfer from Ag to Pd, and reductive elimination (Scheme 2). In light of this proposal, we envisioned that the major problems impeding the execution of the target process would result from the following side reactions: 1) the unstable aryl silver intermediate is liable to protodecarboxylation and decarboxylative homocoupling if the desired cross-coupling reaction Scheme 1. Three examples illustrating the importance of compounds containing a 2-arylthiophene moiety: A natural product (A); Evista (B), a medicine used to prevent and treat osteoporosis; ITPEEPT (C), an electrochromic device.