Arylazoles are ubiquitous features of natural products, pharmaceutics, agrochemicals and fluorescent dyes and this, undoubtedly, plays a key role in the continuing search for the development of new, efficient and cost-effective methods to synthesize these heterocycles. Recently, the transition metal-promoted direct C–H arylation of heteroarenes with (hetero)aryl halides has emerged as an attractive strategy for the effective formation of heteroaryl–(hetero)aryl bonds. In fact, this strategy, unlike the traditional metal-catalyzed cross-coupling procedures involving the use of preformed organometallic reagents, enables the direct elaboration of the heterocyclic cores without the need of preactivating both the coupling partners. In this context, we have been interested in studies aimed to develop efficient protocols for the highly regioselective synthesis of (hetero)aryl azoles by palladium-catalyzed intermolecular direct (hetero)arylation of azoles with (hetero)aryl halides.1 Our studies in this field allowed us the design and development of convenient procedures for the highly regioselective Pd(OAc)2/(2-furyl)3P-catalyzed direct C-5 arylation of 1-aryl-1H-imidazoles, 1-methyl-, 1-benzyl- and 1-methoxymethyl-1H-imidazole with (hetero)aryl iodides and bromides. These arylation reactions were successfully used as key steps of efficient and highly regioselective syntheses of 1,5-, 2,4(5)-, 4,5-diaryl-1H-imidazole derivatives and 2,4,5-triaryl-1H-imidazoles. Interestingly, these new synthetic protocols also allowed us to prepare some interesting bioactive arylazole derivatives, which include several cis-restricted analogues of Combretastatin A-4, a potent and selective antitumor derivative. 1) For a review, see: Bellina, F.; Cauteruccio, S.; Rossi, R. Curr. Org. Chem. accepted for publication.

Regioselective Direct C-5 arylation of Imidazoles: synthetic protocols and applications / F. Bellina, C. Marchetti, R. Rossi, S. Cauteruccio. ((Intervento presentato al 32. convegno Convegno Nazionale della Divisione di Chimica Organica tenutosi a Taormina nel 2008.

Regioselective Direct C-5 arylation of Imidazoles: synthetic protocols and applications

S. Cauteruccio
2008

Abstract

Arylazoles are ubiquitous features of natural products, pharmaceutics, agrochemicals and fluorescent dyes and this, undoubtedly, plays a key role in the continuing search for the development of new, efficient and cost-effective methods to synthesize these heterocycles. Recently, the transition metal-promoted direct C–H arylation of heteroarenes with (hetero)aryl halides has emerged as an attractive strategy for the effective formation of heteroaryl–(hetero)aryl bonds. In fact, this strategy, unlike the traditional metal-catalyzed cross-coupling procedures involving the use of preformed organometallic reagents, enables the direct elaboration of the heterocyclic cores without the need of preactivating both the coupling partners. In this context, we have been interested in studies aimed to develop efficient protocols for the highly regioselective synthesis of (hetero)aryl azoles by palladium-catalyzed intermolecular direct (hetero)arylation of azoles with (hetero)aryl halides.1 Our studies in this field allowed us the design and development of convenient procedures for the highly regioselective Pd(OAc)2/(2-furyl)3P-catalyzed direct C-5 arylation of 1-aryl-1H-imidazoles, 1-methyl-, 1-benzyl- and 1-methoxymethyl-1H-imidazole with (hetero)aryl iodides and bromides. These arylation reactions were successfully used as key steps of efficient and highly regioselective syntheses of 1,5-, 2,4(5)-, 4,5-diaryl-1H-imidazole derivatives and 2,4,5-triaryl-1H-imidazoles. Interestingly, these new synthetic protocols also allowed us to prepare some interesting bioactive arylazole derivatives, which include several cis-restricted analogues of Combretastatin A-4, a potent and selective antitumor derivative. 1) For a review, see: Bellina, F.; Cauteruccio, S.; Rossi, R. Curr. Org. Chem. accepted for publication.
Settore CHIM/06 - Chimica Organica
Regioselective Direct C-5 arylation of Imidazoles: synthetic protocols and applications / F. Bellina, C. Marchetti, R. Rossi, S. Cauteruccio. ((Intervento presentato al 32. convegno Convegno Nazionale della Divisione di Chimica Organica tenutosi a Taormina nel 2008.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/221863
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