Cu(I) and I ₂  as Reagent Combination for the Conversion of β‐Hydroxy Nitroso Scaffolds and Acetophenones into 2‐Ketoaryl Naphthoxazoles: Studies of Antiproliferative Activities

Abstract An effective domino method has been devised toward the preparation of 2‐ketoaryl naphthoxazoles using readily available 1‐nitroso‐2‐naphtholes and 2‐ketoaryl ketones in the presence of Cu(I) and I 2 reagent combination. It has been revealed that a series of substrates were tolerated under the described reaction conditions toward the synthesis of 2‐ketoaryl naphthoxazoles up to 75% yields. The developed method avoids the decarbonylation of synthesized compounds and overcomes the challenges of previously developed processes. The newly synthesized compounds were tested for cytotoxic activities against three cancer cell lines. Among the tested compounds, 3b and 3n exhibited very good activities against leukemia (K562) cell lines with IC 50 values of 11.5 and 22.5 µM, respectively; molecules 3b and 3h have shown good activities against metastatic breast cancer (MDA‐MB‐231), while the rest of the compounds were moderately active. The active compounds can be used as leads for synthesis of more potent anticancer agents.