BF ₃ ·Et ₂ O‐Promoted Annulation of 2‐Propynolphenols With Thiophenols to Yield 2‐Substituted 3‐Sulfenylbenzofurans With Anti‐Prostate Cancer Activities

A BF 3 ·Et 2 O‐promoted cascade annulation of 2‐propynolphenols is described for the synthesis of 2‐substituted 3‐sulfenylbenzofurans. This protocol was achieved through a sequential Meyer–Schuster rearrangement/nucleophilic addition/intramolecular annulation sequence. Mechanistic studies and density functional theory (DFT) calculations provided robust support for the proposed reaction pathway and identified the combined process of the ring‐closing step and the hydrogen transfer process as the rate‐determining step. This method provides an efficient route to C─S bond formation for the assembly of a wide range of 3‐sulfenylbenzofurans in excellent yields under mild conditions. The screening of these 3‐sulfenylbenzofurans against four human cancer cell lines indicated their excellent anticancer activities, wherein compound 3y strongly inhibited prostate cancer cells, with a half‐maximal inhibitory concentration value of 7.24 ± 0.45 µM.