Hydrogen Bonding-directed Sequential 1,6/1,4-Addition of Heteroatom Nucleophiles onto Electron-deficient 1,3-Diynes

A sequential inter- and intramolecular 1,6/1,4-addition on electron-deficient 1,3-diynes conjugated with a ketone, ester, or imide functionality is described. This tandem process is effectively directed by a propargylic -OH or -NH functionality. Alcohols, amines, and thiols show excellent reactivity for the initial 1,6-addition. The addition of amines occurs at ambient temperature, whereas other nucleophiles require high temperatures up to 100 °C and a base additive such as DABCO. Substrates with propargylic hydrogen undergo double bond isomerization at higher temperatures (70-100 °C) to form furan and pyrrole rings. Nonenolizable 1,3-diynones with an electron-withdrawing group provide good yields (72-86%) with most nucleophiles.