Highly Cumulated Radical Cascade Reaction of aza‐1, 6‐Enyenes: Stereoselective Synthesis of exo‐Methylene Piperidines. Issue 11 (11th March 2020)

• Record Type: Journal Article
• Authors: Kamimura, Akio; Itaya, Tomoyuki; Yoshinaga, Tatsuro; Nozawa, Ryo; Kawamoto, Takuji; Sumimoto, Michinori; Uno, Hidemitsu
• Is Part Of: European journal of organic chemistry. Issue 11(2020)
• Page Start: 1700
• Page End: 1707
• Publication Date: 2020-03-11
• Subjects: Radical cascade -- Radical substitution -- 1, 4‐Tin migration -- Piperidine synthesis -- Aza‐1, 6‐Enyne compounds; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.202000034
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract : Treatment of 1, 6‐azaeneyne compounds with Ph3 SnH 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 Ph3 SnH. The product distribution depended on the lower Ph3 SnH 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 Ph3 SnH. Abstract : Triphenyltin radical undergoes radical reaction with aza‐1, 6‐enynes, which leads to a radical addition to alkene, 5‐ exo ‐cyclization, 1, 4‐tin migration, 3‐ exo cyclization, cleavage of cyclopropane, and hydrogen abstraction in one‐pot to give 5‐alkylidene piperidines in a 2, 3‐ cis ‐5‐ exo ‐ E selective manner. Kinetic studies suggest that the 1, 4‐tin migration reaction and ring expansion reaction are very fast, and the rate constants are estimated to be 10 8 s – 1 and 10 5 s – 1 orders, respectively.