A highly stereoselective asymmetric total synthesis of (−)-jimenezin (1), a potent anticancer acetogenin, was efficiently completed with the key feature being a sequential intramolecular amide enolate alkylation (IAEA). Our investigation to probe the origin of the complete stereoselectivity in the second IAEA step to form the conformationally flexible tetrahydrofuran with perfect stereocontrol identified the presence of the oxygen atom in the adjacent tetrahydropyran ring to be crucial.
This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (NRF-2021R1A2C2010431). We are grateful to the Central Laboratory of Kangwon National University for their technical help on both the spectroscopic and spectrometric experiments.
