Asymmetric Total Synthesis and Determination of the Absolute Configuration of (+)-Srilankenyne via Sequence-Sensitive Halogenations Guided by Conformational Analysis
This first asymmetric total synthesis of (+)-srilankenyne (1), a halogenated C15 tetrahydropyran acetogenin isolated from Aplysia oculifera, features a sequence-sensitive process guided by conformational analysis to solve the challenging problem of introducing halogens. A competing semipinacol rearrangement during the installation of C(12)-bromide was suppressed by our A1,3 strain-controlled bromination protocol with support from X-ray crystallographic and computational studies. The C(10)-chloride was then placed by the Nakata chloromesylate-mediated chlorination.
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (NRF-2020R1A2C2010329). We acknowledge the RMACC Summit supercomputer, supported by the NSF (ACI-1532235 and ACI-1532236), and the Extreme Science and Engineering Discovery Environment (XSEDE) allocations TG-CHE180056 and TG-CHE200033.
