Diastereo‐ and Enantioselective Silver‐Catalyzed [3+3] Cycloaddition and Kinetic Resolution of Azomethine Imines with Activated Isocyanides

Abstract In contrast to the well‐established [3+2] cycloaddition reactions, the catalytic enantioselective [3+ n ] ( n ≥3) cycloaddition reaction of activated isocyanides for the preparation of six‐membered or larger ring systems has remained underdeveloped. Herein, we report the first example of highly diastereo‐ and enantioselective [3+3] cycloaddition of activated isocyanides with azomethine imines. By employing silver catalysis, a wide range of biologically important bicyclic 1,2,4‐triazines were obtained in high yields (up to 99 %) with good to excellent stereoselectivities (up to >20 : 1 dr, 99 % ee). In addition, the same catalytic system could be applied to both the late‐stage functionalization of complex bioactive molecules and the kinetic resolution of racemic azomethine imines, further highlighting its versatility and synthetic utility.