The first total synthesis of giffonin H, a highly strained 15-membered macrocyclic diaryl ether, has been achieved in eight linear steps with 10% overall yield. Key steps include Ullmann cross coupling, (Z)-selective Julia-Kocienski olefination, and fluoride-mediated macrocyclization of TMS-Alkyne and aldehyde. In particular, the strategy used for macrocyclization is an unprecedented and unique synthetic approach for cyclic diarylheptanoids. The fluoride-mediated macrocyclization strategy should be applicable to the synthesis of giffonin congeners under mild reaction conditions without affecting the integrity of subtle diene moieties.
Bibliographical noteFunding Information:
This work was supported by the National Research Foundation of Korea (NRF-2015R1D1A1A01056620, NRF-2014M3C1A3054139, NRF-2014M3A9C8024360 and NRF-2018M3A9C8024360).
All Science Journal Classification (ASJC) codes
- Organic Chemistry