Catalytic Ugi-Type Condensation of α-Isocyanoacetamide and Chiral Cyclic Imine: Access to Asymmetric Construction of Several Heterocycles

Abstract

Several novel heterocycles have been constructed asymmetrically on the basis of a catalytic Ugi-type condensation of α-isocyanoacetamide and chiral cyclic imine. The combination of phenylphosphilic acid and trifluoroethanol is exploited to promote an Ugi-type reaction with α-isocyanoacetamide for the first time. By means of this reaction, chiral 3-oxazolyl morpholin-2-one/piperazin-2-one derivatives are synthesized with high yields and excellent stereoselectivities. As electron-rich azadienes, these condensation products are further transformed to fused tricyclic frameworks by treatment with appropriate dienophiles such as maleic anhydride and unsaturated acyl chlorides via domino processes. Moreover, a one-pot, three-component synthesis of the chiral tricyclic frameworks from isocyanoacetamide, imine, and maleic anhydride is also feasible.