Sequential Cu(II)-Catalyzed Multicomponent C–N Coupling, Nucleophilic Addition, and Cyclization Cascade: A Diastereoselective Approach to Carboxamide-Embedded Hexahydrobenzofuran Core

Cascade or domino reactions serve as a powerful technique for the synthesis of complex organic scaffolds in one pot. Herein, a Cu(II)-catalyzed and silica gel-assisted multicomponent reaction (MCR) between bromoalkyne-tethered cyclohexadienones, amides, and water for the construction of hexahydrobenzofuran-3-carboxamide is developed. The reaction proceeds via a C–N coupling reaction followed by hydrative cyclization of ynamide intermediates. Notably, good to excellent diastereoselectivity is complementary of this reaction.