Novel one-pot protocol for the synthesis of unsymmetrical 1,3-diynes

Novel one-pot, fast and efficient protocol was developed to synthesize unsymmetrical 1,3-diynes. The procedure involved two sequential reactions: deprotection of diacetylenic alcohol in a retro-Favorskii reaction to furnish terminal diacetylenic compound, and its coupling with aryl iodides in a Sonogashira cross-coupling reaction catalyzed by Pd(PPh3)4 and CuI using TBAOH as an activator in toluene under reflux for ten minutes. The reaction was optimized as well as the scope and limitations were examined. It was obtained 23 examples with 55 up to 98% yield (Figure 1). It tolerates a variety of functional groups as electron-donating and electron-withdrawing attached to the benzene ring, heterocyclic ring, and alkyl chain. Noteworthy, the unwanted homocoupling product reported to some procedures1 was not detected. The operational simplicity and easy access to diacetylenic alcohol2 prompt us to further study the applicability of 1,3-diynes as intermediates in different transformations.