Synthesis Of2-（Trifluoromethyl）Oxazoles From Enamines Via PhI（OCOCF₃）₂-Mediated Trifluoroacetoxylation

Oxazoles are a class of important heterocycles with various bioactivitiesincluding antibacterial, antiviral and anticancer activities. Also oxazole ring is animportant building block in organic synthesis. Trifluoromethyl group could modifythe physical-chemical characters and bioactivities of some molecules, and is animportant functional group in the pharmaceutical development. However, accordingto the literature, only a few methods to synthesize such compounds have beenreported, most of which chose trifluoromethyl acid or trifluoromethyl acidicanhydride as fluorine sources. In this project, we choose the hypervalent iodinereagent [bis(trifluoroacetoxy)iodo] benzene (PIFA) as the fluorine source. So we haveprovided a novel method with mild reaction condition, easy workup and moderateyield to synthesize2-trifluoromethyl oxazoles.In this project the substrates-monosubstituted enamines reacted with PIFA inDCE at45oC. Trifluoacetate group was incorporated into the final product viatrifluoroacetoxylation on the-position of the enamines. Then the oxazole ring wasformed via intramolecular condensation and cyclization.In this project we have successfully synthesized a series of2-trifluoromethyloxazoles, including4-aryl or alkyl-5-carbonyl or ester groups substituted oxazoles.All the structures of these oxazoles were identified by1H,13C,19F-NMR and HRMS.The model oxazole has been identified by X-ray single crystal diffraction analyses.Also we have analyzed the mechanism and approved it through experiments.