Azoles are ubiquitous features of natural products, pharmaceuticals and fluorescent dyes as well as many other synthetics, and this, undoubtedly, plays a key role in the continued search for the development of new, efficient and cost-effective methods for the synthesis of these heterocycles. In particular, great attention has been paid in the last years to the selective functionalization of C–H and N–H bonds of five-membered heterocycles via direct transition metal-mediated C- and/or N-arylation with aryl halides. In this context, we recently found that a variety of 1,5-diaryl-1H-imidazoles 1 can be regioselectively prepared in moderate yields by a Pd-catalyzed direct coupling of 1-aryl-1H-imidazoles 2 with aryl halides 3 in the presence of CsF. Subsequently, we prepared 5-aryl-1-methyl-1H-imidazoles 3 and 5-aryl-1-benzyl-1H-imidazoles 4 by a protocol similar to that used for compounds 1. We also found that 1,2-diaryl-1H-imidazoles 5 can be regioselectively prepared from compounds 2 and halides 3 in the presence of CsF and CuI and a catalytic amount of Pd(OAc)2. More recently, we have developed a new and convenient protocol for the regioselective Pd- and Cu-mediated C-2 arylation of a variety of azoles, including free (NH)-imidazole, -benzimidazole and -indole, under base-free and ligandless conditions, and we have employed this procedure for the preparation of 2,4(5)-diaryl-1H-imidazoles 6 via reaction sequences involving the C-2 arylation of the corresponding 4(5)-aryl-1H-imidazoles 7 or compounds 4. Interestingly, 4,5-diaryl-1H-imidazoles 8 and 4,5-diaryl-1-methyl-1H-imidazoles 9 have also been obtained from 4 and 3, respectively, via a two-steps sequence involving a regioselective C-4 halogenation and a Suzuki-type reaction. Finally, in the course of our studies on the direct C- and N-arylation of azoles we have observed a complete switch from C-2 to N-1 arylation performing the reaction of indole with aryl iodides under ligandless and base-free conditions in the presence of CuOAc instead of CuI and omitting Pd. Mechanistic proposals for our arylation protocols and some their applications to the synthesis of biologically interesting heterocyclic derivatives will be also reported and discussed.
Development and applications of new protocols for the direct and regioselective arylation of azoles / F. Bellina, C. Calandri, S. Cauteruccio, A. Di Fiore, R. Rossi. ((Intervento presentato al 22. convegno European Colloquium on Heterocyclic Chemistry tenutosi a Bari nel 2006.
|Titolo:||Development and applications of new protocols for the direct and regioselective arylation of azoles|
|Data di pubblicazione:||2006|
|Settore Scientifico Disciplinare:||Settore CHIM/06 - Chimica Organica|
|Citazione:||Development and applications of new protocols for the direct and regioselective arylation of azoles / F. Bellina, C. Calandri, S. Cauteruccio, A. Di Fiore, R. Rossi. ((Intervento presentato al 22. convegno European Colloquium on Heterocyclic Chemistry tenutosi a Bari nel 2006.|
|Appare nelle tipologie:||14 - Intervento a convegno non pubblicato|