Ternary Synthon Strategy for 1,3,5-Trisubstituted Benzenes via [3 + 3] Benzannulation of Propargyl Alcohols

The efficient synthesis of polysubstituted benzenes is an important goal in organic chemistry, yet the synthesis of 1,3,5-trisubstituted benzene derivatives remains challenging due to the absence of robust and efficient synthetic methods. Organic peroxides, typically employed as oxidants or monosynthons in organic reactions, have never been explored as multiple synthons, marking a void in the current research landscape. Herein, we report the first synthesis of 1,3,5-trisubstituted benzene derivatives under metal-free catalytic conditions using a [3 + 3] benzannulation strategy of propargyl alcohols with organic peroxides as three-carbon synthons. In addition, the combined experimental and density-functional theory (DFT) calculations results demonstrate that the product formation occurs through a sequence of processes consisting of the propargyl alcohol activation, the generation of olefins, an acid assisted [3 + 3] cyclization and oxidative aromatization.