Highly Cumulated Radical Cascade Reaction of aza‐1,6‐Enyenes: Stereoselective Synthesis of exo‐Methylene Piperidines

Abstract

Treatment of 1,6‐azaeneyne compounds with Ph3SnH resulted in the stereoselective formation of 5‐(E)‐alkylidene‐2,3‐cis‐piperidine in moderate to good yields. Intermediate products including methylenepyrrolidine and stannomethylene pyrrolidine were also detected in the reaction mixture, suggesting that the reaction progressed via a highly cumulated radical cascade process involving sequential six radical processes, i.e. radical addition, 5‐exo cyclization, substitution (1,4‐tin migration), 3‐exo cyclization, ring cleavage of cycloprolane, and hydrogen abstraction from Ph3SnH. The product distribution depended on the lower Ph3SnH concentration, resulting in higher piperidine yields. The E/Z selectivity of the exo‐methylene unit was also sensitive to the reaction temperature. The vinylic triphenyltin group was converted into hydrogen and iodine. A kinetic analysis of the reaction indicated that the 1,4‐tin migration and ring expansion progressed as irreversible reactions and that their reaction rates were large enough to progress the cascade reaction smoothly and to prevent side reactions such as hydrogen abstraction from Ph3SnH.