Diverse reactivity by coupling of substituted anilines with ethyl trifluoropyruvate was developed under microwave irradiation without catalysts to generate 3-trifluoromethyl-3-hydroxy oxindoles, aromatic hydroxy trifluoromethyl esters, and 1,2-dicarbonyl compounds in a fast and efficient manner. The plausible mechanism for obtaining different products was proposed. Furthermore, the anti-HIV activity of aromatic hydroxy trifluoromethyl esters was first reported. The best inhibitory activity against wild-type HIV-1 IIIB was exemplified by trifluoromethyloxindole 3q with an IC50 = 5.8 μM, which also displayed potential activity against Y181C mutant virus with an IC50 = 7.5 μM. More significantly, the activities of oxindoles 3q and 3r to inhibit K103N/Y181C double mutant HIV-1 reverse transcriptase (RT) are probably similar to that of the second-generation nonnucleoside inhibitor HBY 097 by docking calculation.