Base‐Catalyzed Unexpected Cyclization of β ‐Trifluoromethyl 2′‐Hydroxychalcones: Novel Synthesis of 2‐Substituted Benzofuran‐3(2 H )‐Ones

The introduction of a trifluoromethyl group into the β ‐position of 2′‐hydroxychalcones completely changes the direction of the cyclization process. DBU‐catalyzed reaction of β ‐trifluoromethyl 2′‐hydroxychalcones under mild conditions provides regioselectively 2‐substituted α ‐trifluoromethyl‐benzyl benzofuran‐3(2 H )‐ones, typically in good yields (80%–93% after 0.5 h) and dr close to 4:1. However, relatively small changes in substrate structure at the β ‐position, e.g., replacement of CF 3 with CF 2 H or a phenyl with a cyclohexyl group, lead to the formation of chroman‐4‐one framework. Moreover, 2′‐hydroxychalcones containing CF 2 Cl or CF 2 CF 3 group cyclize to a five‐membered ring with elimination of hydrogen halide. Results of DFT calculations explain the reaction course and how the selectivity of the reaction is influenced by electronics and geometries of the substrates, intermediates, and transition states.