α-Nitroacetophenones enabled the efficient synthesis of 2-acylbenzofurans via organocatalytic bond-forming sequential control.

Abstract

Controlling the order of C-C and C-O bond formation provides an effective strategy for developing alternative routes to furan heterocycles. Herein, we report an α-nitroacetophenone-enabled organocatalytic approach for the synthesis of 2-acylbenzofurans from 2-hydroxycarbonyl compounds. Using an aniline-derived organocatalyst in a choline chloride-urea deep eutectic solvent (DES), the reaction proceeds at room temperature under base- and metal-free conditions, affording target products in excellent yields of up to 95%. In contrast to conventional α-haloketone-based protocols that initiate via C-O bond formation followed by C-C coupling, the present strategy proceeds through a reverse sequence where C-C bond formation precedes intramolecular C-O cyclization. Control experiments, FT-IR, and HRMS analyses support this proposed pathway. Furthermore, the organocatalyst and DES medium were successfully recovered and reused across five consecutive cycles with sustained efficiency. These findings demonstrate that α-functional group selection can govern the bond-forming sequence in heterocycle synthesis.

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