5- fluoro-2- oxazole

Chemical Name 21 -(Acetyloxv)-9-fluoro-11 -hvdroxv-2 -methyl-5 H-pregna-1,4-dieno-[17,16-d] oxazole-3 0-dione... 

CN (lip,16(i)-21-(acetyloxy)-9-fluoro-ll-hydroxy-2 -methyl-5 H-pregna-l,4-dieno[17,16-d]oxazole-3,20-dione... 

Malonamid-ale 4-Fluoro-a-[(hydro-xymeihylamino)-benzyliden]-E15/1.682 (aus dcm 4.5-H, — 1,2-oxazol/hr)... 

CN (11 (3,16 3)-21 -(acetyloxy )-9-fluoro-11 -hydroxy-2 -methyl-5 //-prcgna-1,4-dienof 17,16-d]oxazole-3,20-... 

A wide variety of a-trifluoromethyl-substituted amino acids are now available from the reaction of 5-fluoro-4-trifluoromethyl-l,3-oxazoles with allylic alcohols and benzyl alcohols. The reaction sequence involves a low-temperature Claisen rearrangement or a radical 1,3-benzyl shift from oxygen to carbon, respectively [88AG(E)848 89S850] (Scheme 86). 

Transition metal compounds can be replaced by other substances, for example, by phosphites. Thus, 2-substituted 4-trifluoromethyl-5-fluoro-l,3-oxazole-2,4-dienes 9 were obtained by the reaction of 4,4-bis(trifluoromethyl)-N-acylimine 10 with trimethylphosphite (71CB1826, 74CB1448). The reaction occurs via the intermediate formation of 5-substituted 3,3-bis(trifluoromethyl)-2,2-dihydro-1,4,2-oxazaphos-pharol-4-ene 11 (Scheme 15). 

Reddy, A.C.S. Rao, P.S. Venkataratnam, R. V. Fluoro organics facile syntheses of novel 2-or 4-trifluoromethyl-l//-arylo-l,5-diazepines, oxazepines, thiazepines, 2-(l,l,l-trifluor-oacetonyl)imidazoles, oxazoles and thiazoles. Tetrahedron 1997, 53(16), 5847-5854. 

The authors adapted this methodology to prepare 3,3,3-trifluoroalanine 220. Benzamide was first converted to 217 (Ar = CgHs) followed by reductive cyclization to 5-fluoro-2-phenyl-4-(trifluoromethyl)oxazole 218 (Ar = C6H5). Displacement of fluoride in 218 gave 5-ethoxy-2-phenyl-4-(trifluoromethyl)oxazole 219, which was converted to 220 with iodotrimethylsilane (Scheme 1.61). 

Burger and co-workers extensively investigated the syntheses and reactions of 2-alkyl(aryl)-5-fluoro-4-(trifluoromethyl)oxazoles 218. They found that 218 react with a variety of oxygen, nitrogen, sulfur, and carbon nucleophiles to afford substitution products 646 in modest to excellent yield (Scheme i 173) 262,264,265 Representative examples are shown in Table 1.49. 

These same authors observed a similar reactivity pattern with 5-fluoro-2-heteroaryl-4-(trifluoromethyl)oxazoles 650. The starting materials were readily prepared from a heterocyclic amide according to their earlier protocol. Here again, displacement of fluoride in 650 was readily accomplished to afford 651, 652 and 653 (Scheme 1.179). 

TABLE 1.50. A/-BENZOYL-a-(TRIFLUOROMETHYL) AROMATIC a-AMINO ACIDS FROM 5-FLUORO-2-PHENYL-4-(TRIFLUOROMETHYL)OXAZOLE ... 

In 5-fluoro-4-trifluoromethyl oxazoles, the F JcFj-f couplings are generally 10-15 Hz (vide supra). nd, not determined. 

TABLE 1.49 2-ARYL-5-SUBSTITUTED 4-(TRIFLUOROMETHYL)OXAZOLES FROM NUCLEOPHILIC SUBSTITUTION OF 2-ARYL-5-FLUORO-4-(TRIFLUOROMETHYL) OXAZOLES, 142... 

Hilborn et al. demonstrated the synthesis of PBOs (Figure 5.29) by polymerization of bis(fluorophenyl benzoxazoles) with bisphenols. This polymerization was based on the activation of the fluoro group toward nucleophilic aromatic substitution by the oxazole component of the benzoxazole heterocyclic [51]. The TgS of the poly(arylene ether benzoxazoles) ranged from 213 to 303 °C, depending on the bisphenol and activated dihalide used in the synthesis. Generally, the TgS increased with the bulkiness of the bisphenol used. The polymers containing the >C(CF3)2 unit in both the benzoxazole and the bisphenol moiety in the monomers showed higher solubility (NMP) compared to the other PBOs. The physical properties of fluorinated poly(arylene ether benzoxazole) s are presented in Table 5.3. 

Keywords Fluoro- and fluoroalkyl-oxazoles -benzoxazoles -Ihiazoles -selenazoles -benzothiazoles... 

Fluoro-2-perfluoroalkyl-4-(trifluoromethyl)oxazoles were formed by reduction of perfluoroacyUmines with some metals. The reaction is promoted by catalytic amounts of Cul salts and crown ethers. Among the metals (magnesium, tin, aluminum, and zinc) only zinc and tin exerted as a defluorinating effect. The best yields of oxazoles were attained in the presence of zinc [22, 23]. A similar single electron transfer mechanism was described for cyclization of other hexafluoroacetone imines with metals. The role of crown ether is apparently reduced to the assistance in the elimination of ZnF with formation of 0-anion, which results in the intramolecular cyclization to oxazoles. 

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