Benzo oxazole, arylation

The recent literature presented some improvements of the known procedures rather than new synthetic approaches. An efficient and more sustainable protocol for the copper-catalysed intramolecular O-arylation of ortho-halo anilides to afford benzo[<7]oxazoles has been described. After an optimization process, the best conditions were the use of CuCl and TMEDA in water... 

Ohta and co-workers carried out extensive studies on intermolecular arylation of various heterocycles (furan, thiophene, pyrrole, oxazole, thiazole, A-methylimi-dazole, benz[fe]oxazole, benzo[i>]furan, and benzo[ ]thiophene) with mainly chlo-ropyrazines as heteroaryl halides using Pd(PPh3)4 and AcOK [3]. 

Most reactive sites in thiazoles, oxazoles, and imidazoles are electron-rich C-5 positions. If C-5 positions are blocked, less reactive C-2 positions are arylated. Also arylation of their benzo derivatives occurs at C-2. 

The first example of C—H arylation of (benz)oxazoles (20 examples 23—92% yield) and (benzo)thiazoles (3 examples 43—97% yield) with easily accessible aryltrimethylammonium triflates was recendy reported by Wang and coworkers (2015OL4926). The researchers evaluated a catalyst system... 

These include the SSA-catalyzed synthesis of heterocyclic compounds such as xanthenes, coumarins, oxazoles, and so on. Xanthenes are of great therapeutic and biological interest on account of their many biological activities such as anti-inflanunatory, antiviral, antibacterial properties, and so on. Seyyed Hamzeh et al. (2008) carried out the SSA-catalyzed synthesis of aryl-14 f-dibenzo[fl,y]xanthenes from aldehydes and P-naphthol and 1,8-dioxo-octahydro-xanthenes from aldehydes and 1,3-dicarbonyl componnd such as dimedone under solvent-free conditions (Schemes 5.25, 5.26). Reactions were carried out at 80°C. Nazeruddin et al. (2011) documented an effective method for 9,10-dihydro-12-aryl-8 f-benzo[a]xanthenes-ll(12 f)-one derivatives in excellent yield and short reaction time using SSA under solvent-free conditions (Scheme 5.27). 

C2-Arylated 1,3-Azoles In 1998, Miura reported the first example of the catalytic C-H arylation of (benzo)azoles and thiophenes (at their C2 position) with aryl halides [98, 99a]. In the presence of catalytic Pd(OAc)2 and stoichiometric carbonate base at high temperature (140 °C), 1,3-azoles (oxazoles, N-alkylated imidazoles, fhiazoles) were coupled with various aryl bromides selectively at the C2 position. For the reactions of N-alkylated benzimidazoles, benzoxazoles, and benzothiazoles, addition of Cul was necessary to increase the yield of products. Furthermore, when N-methylbenzimidazole was used, Miura discovered that the coupling with aryl bromides proceeds without the palladium catalyst (i.e., by a copper-mediated C-H/C-X coupling of azoles with aryl halides). Thereafter, Miura enhanced the efficiency of the coupling reaction to allow for multiple arylations of azoles both C2 and C5 positions [99b]. In 2000, Rondo [100] prepared polymer-supported aryl iodides, with which the direct coupling reaction with 1,3-azoles (Miura s conditions) was conducted. 

A novel Pd(OAc)2-NFSI-TFA system was developed recently by Xu and cowoilc-ers demonstrating highly selective, ortto-monofluorination. In this case Pd coordination was directed by a diverse range of aryl-Af-heterocyclic directing groups (Scheme 9.15), such as quinoxaline, pyrazole, benzo[rf]oxazole, and pyrazine derivatives. A Pd(ll/IV) catalytic cycle was proposed. 

Sun et al. reported a diversity-oriented tactic to access the benzo[d]oxazol-5-yl-lH-benzo[d]imidazole 64 on IL support (Scheme 24). The authors coupled 4-hydroxy-3-nitrobenzoic acid onto IL-immobilized o-phenylenediamine 58 that underwent ring closure to furnish benzimidazole derivatives 60. Further hydrogenation of the nitro group to an amine followed by the reaction with 1,1-thiocarbonyldiimidazols resulted into IL tagged-benzoxazol 63. In order to generate skeletal diversity, S-alkylation with alkyl and aryl bromides was carried out. Cleavage of 64 from IL support was done by treatment with sodium methoxide in methanol imder microwave irradiation [127]. 

Jung, M.E. and Dansereau, S.M.K. (1994) Benzo[H]-l,6-naphthyridine synthesis via intramolecular Diels-Alder reactions of aryl oxazoles synthetic approach to 2-bromoleptoclinidinone. Heterocycles, 39, 767-778. 

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