Thursday, July 28, 2022 - 2:30pm


This dissertation describes our efforts towards a total synthesis of the isocyanoterpene natural product, isoneoamphilectane. We hypothesized a potential structural revision that guided our synthetic design and motivated the synthesis of two diastereomers of the reported natural product: 7,8-di-epi-isoneoamphilectane and 8-epi-isoneoamphilectane. With greater insight into the natural product’s stereochemical assignments, we embarked on a synthesis of isoneoamphilectane hinging on a challenging cis-to-trans decalone epimerization. We investigated multiple contrathermodynamic epimerization strategies and discovered a cyclic sulfite-based pinacol-like rearrangement to install the strained ring system. Additional key steps in our synthesis include an acyclic Mukaiyama–Michael addition, an intramolecular alkoxide-directed elimination, and an HAT-mediated alkene hydroazidation. In conclusion, we report the first total synthesis of isoneoamphilectane in 22 steps from known materials.


Natalie Dwulet


NS2 2201