Iridium-Catalyzed Reductive (3+2) Annulation of Lactams Enabling the Rapid Total Synthesis of (±)-Eburnamonine
Yasukazu Sugiyama1, Kento Yamada1, Daiki Kaneko1
1Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1, Hiyoshi, Kohoku-ku, Yokohama, 223-8522, Japan.
Abstract:
A reductive (3+2) annulation of lactams through iridium-catalyzed hydrosilylation and photoredox coupling with α-bromoacetic acid was developed. The iridium-catalyzed hydrosilylation of the lactam carbonyl group and subsequent elimination provide a transient cyclic enamine, which undergoes iridium-catalyzed photoredox coupling with α-bromoacetic acid in a one-pot process. The developed conditions show high functional-group tolerance and provide cyclic N,O-acetals containing a quaternary carbon center. The resulting N,O-acetals undergo a variety of acid-mediated nucleophilic addition reactions via iminium ions to give substituted cyclic amines. The developed sequence including reductive (3+2) annulation and acid-mediated nucleophilic addition was successfully applied to the four-step total synthesis of (±)-eburnamonine.
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