10.1016/0040-4039(96)01924-7
The study presents the first synthesis of cis-enediynes from 1,5-diyne 7 through an acid-mediated allylic rearrangement using (+)-10-camphorsulfonic acid (CSA) in CH2Cl2 at 20 °C in the presence of ROH or RSH. The key chemicals involved include the starting material 1,5-diyne 7, which is prepared from a-bromocinnamaldehyde (5) via cross-coupling with H2C(CH2)4OMe and subsequent addition of LiCCCH2SiMe3. The reaction yields cis-enediyne 10 as the major product, along with trans-enediyne 8 and 1,5-diyne 9. The study also explores the allylic rearrangement in the presence of various nucleophiles (ROH and RSH), achieving high regioselectivity and trans/cis stereoselectivity. The synthesized cis-enediynes can be oxidized to form diradicals capable of DNA cleavage. Additionally, an 11-membered ring enediyne 15 is synthesized using a similar acid-promoted allylic rearrangement strategy, highlighting the potential for enediyne prodrug design and synthesis.