Domino Cyclization/Trifluoromethylation of 2-Alknylphenols for the Synthesis of 3-(Trifluoromethyl)benzofurans and Evaluation of their Antibacterial and Antifungal Activities

Herein, we describe a one-step synthesis of pharmaceutically relevant 3-(trifluoromethyl)benzofurans from readily accessible 2-alkynylphenols. The method utilizes a domino cyclization/trifluoromethylation strategy with [CuCF3] as a reagent. The CF3 source is the low-cost industrial byproduct fluoroform (CF3H). The assays for antifungal and antibacterial activities conducted on these fluorinated benzofuran derivatives revealed that all were devoid of hemolytic activity toward rabbit erythrocytes indicating absence of toxicity. One of the compounds, 2g, containing a 4-NH2C6H4 moiety at the C-2 position of the benzofuran core, demonstrated suppressive activity against the fungal pathogens Candida albicans, C. glabrata, and the bacterium methicillin-resistant Staphylococcus aureus, showing minimal inhibitory concentrations (MICs) of 64 mu M, 128 mu M, and 128 mu M, respectively. Incubation of Candida cells with 2g elicited a time-dependent accumulation of reactive oxygen species (ROS).