Synthesis of cyano-substituted γ-lactams through a copper-catalyzed cascade cyclization/cyanation reaction

A convenient copper-catalyzed cascade cyclization/cyanation reaction for the construction of cyano-containing γ-lactams was developed. The protocol employed TMSCN as the cyano source and proceeded in water under simple conditions. Mechanistic studies indicated this reaction involved an amidyl radical initiated cascade 5- exo-trig cyclization/cyanation process. It is capable of generating a series of cyano-substituted γ-lactams and relative 2-oxazolidinone derivatives with a broad substrate scope. A copper-catalyzed cascade cyclization/cyanation of N -aryl-4-pentenamides with TMSCN was developed. The reaction proceeded in water under simple conditions to generate a series of cyano-substituted γ-lactam derivatives.