Regioselective Synthesis of Acyclic cis-Enediynes via an Acid-Catalyzed Rearrangement of 1,2-Dialkynylallyl Alcohols. Syntheses, Computational Calculations, and Mechanism†

A novel synthesis of acyclic cis-enediynes 2 has been established by an acid-catalyzed rearrangement of 1,2-diyn-2-propen-1-ols 1 possessing a C3-aryl group in the presence of water, alcohols, or thiols. Reactivity of allyl alcohols and regio- and cis/trans diastereoselectivity of the allylic migration were examined. In the presence of (±)-10-camphorsulfonic acid (CSA), the parent allyl alcohol 5 and the C3-methyl-substituted 9 failed to give enediynes, whereas the C3-aryl-substituted 12 and 29 underwent the allylic rearrangement to provide predominantly cis-enediynes 16 and 31 at room temperature or below. Under similar acidic conditions, enediyne alcohol 13 produced 16b and 16d with the same regio- and cis/trans diastereoselectivity observed for 12. Allyl alcohol 30, an isomer of 29, also provided enediynes 31c and 32c after a prolonged reaction (90 h) at room temperature in the presence of CSA and EtOH. These results suggested that the same allylic cations were obtained from allyl alcohols 12 and 13 or...