Progress Toward a Total Synthesis of the Lycopodium Alkaloid Lycopladine H

Open Access
Sacher, Joshua Ryan
Graduate Program:
Doctor of Philosophy
Document Type:
Date of Defense:
Committee Members:
  • Steven M Weinreb, Dissertation Advisor
  • Raymond Lee Funk, Committee Member
  • Gong Chen, Committee Member
  • Ryan John Elias, Committee Member
  • organic
  • synthesis
  • lycopodium
  • lycopladine
  • quinone ketal
  • oxidative dearomatization
  • hydroaminomethylation
  • Henry reaction
In work directed toward a total synthesis of the Lycopodium alkaloid lycopladine H (21), several strategies have been explored based on key tandem oxidative dearomatization/Diels-Alder reactions of o-quinone ketals. Both intra- and intermolecular approaches were examined, with the greatest success coming from dearomatization of bromophenol 84b followed by cycloaddition of the resulting dienone with nitroethylene to provide the bicyclo[2.2.2]octane core 203 of the natural product. The C-5 center was established via a stereoselective Henry reaction with formaldehyde to form 228, and the C-12 center was set through addition of vinyl cerium to the C-12 ketone to give 272. A novel intramolecular hydroaminomethylation of vinyl amine 272 was used to construct the 8-membered azocane ring in intermediate 322, resulting in establishment of 3 of the 4 rings present in the natural product 21 in 9 steps from known readily available compounds.