Oxazoles, arylation

Dewar and Turchi carried out similar rearrangements of secondary and tertiary alkyl and aryl oxazole-4-carboxamides (5a-e) to the corresponding secondary and tertiary 5-aminooxazoles (6a-e). For example, they realized yields > 90% when the amide nitrogen is part of a heterocyclic ring system. 

The tosyl compound reacts with aldehydes in the presence of potassium carbonate to yield 5-alkyl- or 5-aryl-oxazoles, the intermediate dihydrooxazoles (which can be isolated) eliminating toluene-p-sulfinic acid (Scheme 30). Use of acyl chlorides in place of aldehydes leads to 4-tosyloxazoles (288). Furthermore, alkylation of tosylmethyl isocyanide with an alkyl halide RfX, followed by treatment with an aldehyde R2CHO, yields a 4,5-disubstituted oxazole (289). A related reaction is that of A-tosylmethyl-iV -tritylcarbodiimide with aromatic aldehydes under phase-transfer catalysis to yield 2-tritylaminooxazoles which are readily converted into 2-amino-5-aryloxazoles (equation 117) (81JOC2069). 

When jV-protected indole-3-carboxaldehydes were allowed to react with tosylmethyl isocyanide, 3-(oxazol-5-yl)-indoles were obtained in satisfactory yields and applied to the synthesis of novel indole-based IMPDH inhibitors <02BMCL3305>. In the same context, a modified approach to 2-(JV-aryl)oxazoles employing an iminophosphorane/ isothiocyanate-mediated methodology and its application to the synthesis of the potent IMPDH inhibitor BMS-337197, was reported <020L2091>. 

Oxazolones undergo Friedel-Crafts reactions with aromatic compounds to give keto intermediates which, under the reaction conditions, cyclodehydrate to give 5-aryl-oxazoles (Equation 7) <2005JOC4211>. 

Moreover, aryl-oxazoles, -imidazoles [17], or-thiazoles [18], anhydrides [19], and imides [20] are accessible via intramolecular Heck-type carbonylations. In addition to typical acid derivatives, aldehydes [21], ketones [22], aroyl cyanides, aroyl acetylenes, and their derivatives [23] could be synthesized via nucleophilic attack of the acyl metal complex with the corresponding hydrogen or carbon nucleophiles. Even anionic metal complexes like [Co(CO)4] can act as nucleophiles and lead to aroylcobalt complexes as products [24]. 

Oxazoles can be arylated at either C-2 or C-5, the method shown being notable for the use of water as solvent. 2-Substitution of 5-aryl oxazoles, using palladium acetate, can be carried out without an added ligand. ... 

Oxazoles and 4,5-dihydrooxazoles can be transformed into quinolines. For instance, 5-(o-acylamino-aryl)oxazole-4-carboxylic esters 104, made from benzoxazinones 103 and isocyanoacetic ester, are converted into 3-aminO 4-hydroxy-2-quinolones 105 in an acid medium [109]. 

PS-p-toluenesulfonylmethyl isocyanide (TosMIC) reagent, developed by Barrett et al. was found to be effective for the conversion of a range of aryl aldehydes into highly pure 4-aryl oxazoles in the presence of BTMG (2) [79] (Scheme 4.29b). A typical procedure involved the reaction of aldehyde with the gel (4 equiv.) in acetonitrile (0.2M sol) and BTMG (2) (4 equiv.) for 12 h at 65 °C. ... 

TABLE-1.3. 2-ALKYL(ARYL)OXAZOLES BY REARRANGEMENT OF N(1)-ACYL-1,2,3-TRIAZOLES ... 

This reaction was extended to prepare other 2-alkyl(aryl)-oxazoles 82 in modest to excellent yields (Table 1.3). The low yield obtained for the bis-oxazole (Table 1.3, entry 4) resulted from difficulties encountered with isolation of the product from sulfolane. 

TABLE 1.24. 2-ALKYL-, 2,4-DIALKYL-, AND 2-ALKYL-5-ARYL-OXAZOLES LROM PYROLYSIS OL CYCLIC ENAMINOESTERS"... 

TABLE 1.40. 2-ALKYL(ARYL)OXAZOLES VIA RETRO-DIEES-AEDER REACTION"... 

TABLE 1.73. 2-ALKENYL(ARYL)OXAZOLES OR 2-ALKENYL(ARYL)-5-SUBSTITUTED OXAZOLES FROM PALLADIUM-CATALYZED CROSS-COUPLING OF OXAZOL-2YLZINC CHLORIDES"... 

TABLE 1.40 2-AEKYL(ARYL)OXAZOLES VIA RETRO-DIELS-ALDER REACTION, 123... 

Jefferys has modified the Davidson oxazole synthesis by using phenacyl bromides and ammonium acetate to yield 2-methyl-4-(or 4,5-di-)-substituted oxazoles. He was also able to extend the syntheses outlined by Japp and Davidson to obtain 4,5-dialkyl and 4-aryl oxazoles. These oxazoles together with 2-methyloxazole were then quatemized and transformed into cyanine and merocyanine dyes. 

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. 

---