Heteroaromatics are important structural units frequently found in natural products, pharmaceutics, agrochemicals, and organic functional materials such as liquid crystals and fluorescent dyes. Due to their widespread applications, the development of straightforward functional group-tolerant methods for their preparation in high yield under mild conditions has aroused considerable attention. Recently, the transition metal-catalyzed direct arylation of heterocycles with aryl halides emerged as an attractive strategy for the effective construction of aryl–aryl bonds which, unlike the traditional metal-catalyzed cross-coupling strategies involving preformed organometallic reagents, enables direct elaboration of heterocyclic cores without the obligation to use coupling partners that are both preactivated. Over the last years, we have been interested in studies aimed to broaden the substrate scope of the direct arylation of -electron-rich heteroarenes and, in particular, to develop efficient protocols for the highly regioselective synthesis of (hetero)aryl azoles by palladium-catalyzed intermolecular and intramolecular direct (hetero)arylations of azoles with (hetero)aryl halides. These studies allowed us to develop efficient protocols for: a) highly regioselective Pd-catalyzed C-5 direct arylation of 1-methyl-, 1-benzyl-, 1-methoxymethyl-1H-imidazole and 1-aryl-1H-imidazoles; b) highly regioselective ligandless Pd-catalyzed and Cu-mediated direct C-2 arylation of 1-aryl-1H-imidazoles; c) a convenient base-free and ligandless regioselective Pd-catalyzed and Cu-mediated direct C-2 arylation of several azoles, including free NH-imidazole, benzimidazole and -indole. We will report the results of these studies and will discuss mechanistic proposals for our arylation protocols, which we successfully applied to the highly regioselective preparation of a variety of 1,5-diaryl-1H-imidazoles, 2,4- and 4,5-diaryl-1-methyl-1H-imidazoles, 5-aryl-1H-imidazoles, 2,4- and 4,5-diaryl-1H-imidazoles. It should be noted that these synthetic protocols allowed us also to prepare some interesting bioactive arylazole derivatives, including several cis-restricted analogues of Combretastatin A-4, a potent and selective antitumor derivative. Finally, it is worth mentioning that we developed intramolecular versions of our regioselective direct C-H arylation protocols that permitted efficient access to interesting tricyclic heteroaromatics, including 5H-imidazo[5,1-a]isoindole and 5H-imidazo[2,1-a]isoindole derivatives.
|Titolo:||Arylazole derivatives by highly regioselective direct C-H arylation reactions|
|Data di pubblicazione:||2008|
|Settore Scientifico Disciplinare:||Settore CHIM/06 - Chimica Organica|
|Enti collegati al convegno:||Royal Society of Chemistry|
Società Chimica Italiana
|Citazione:||Arylazole derivatives by highly regioselective direct C-H arylation reactions / F. Bellina, F. Benelli, S. Cauteruccio, A. Di Fiore, C. Marchetti, F. Scalesse, R. Rossi. ((Intervento presentato al 11. convegno RSC-SCI Joint Meeting on Heterocyclic Chemistry tenutosi a Lerici (SP) nel 2008.|
|Appare nelle tipologie:||14 - Intervento a convegno non pubblicato|