A Concise Total Synthesis of (-)-Himalensine A

The daphniphyllum alkaloids are a structurally fascinating and remarkably diverse family of natural products. General strategies for the chemical synthesis of their challenging architectures are highly desirable for efficiently accessing these intriguing alkaloids and addressing their pharmaceutical potential. Herein, a concise strategy designed to provide general and diversifiable access to various daphniphyllum alkaloids is described and utilized in the asymmetric synthesis of (-)-himalensine A, which was accomplished in 14 steps. Key features of this strategy include a Cu-catalyzed nitrile hydration, a Heck reaction to construct the challenging 2-azabicyclo[3.3.1]nonane motif, a Meinwald rearrangement reaction, six, pot-economic reactions, and the minimal use of protecting groups, which significantly improved the overall synthetic efficiency.