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Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
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Asymmetric Total Synthesis of Norzoanthamine
Zhengyuan Xin1, Hui Wang1, Haibing He2
1Shanghai Key Laboratory of Green Chemistry and Chemical, Processes, School of Chemistry and Molecular Engineering, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062, China.
Abstract:
We report herein the asymmetric total synthesis of norzoanthamine using radical reactions as key steps for rapid access to the congested carbocyclic core, which is the major synthetic challenge for most zoanthamine alkaloids. (1) The Ueno-Stork radical cyclization was applied to construct the adjacent quaternary centers at the C-9 and C-22 positions; (2) a Co-catalyzed HAT radical reaction was successfully applied to construct the quaternary center at C-12 via Csp3 -Csp2 bond formation; (3) a Mn-catalyzed HAT radical reaction was used to stereospecifically reduce the tetra-substituted olefin (C13=C18) and install the contiguous stereocenters in proximity to the quaternary center. A one-pot bio-inspired cyclization step was finally applied to forge the unstable bis-amino acetal skeleton. Our approach can precisely control the stereochemistry of seven vicinal stereocenters and effectively construct the highly congested heptacyclic skeleton.
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