Progress in using calcium carbide as acetylide source in ethynylation methods of various substrates

Terminal alkynes have found great applications in the synthesis of complex molecules in medicinal chemistry and agrisciences. This study aims to design practical ethynylation methods for various substrates using calcium carbide&mdash;an abundant, affordable acetylide source. Inspired by a fluoride-assisted activation of calcium carbide with ketones and subsequent retro-Favorskii reaction, we hypothesized that ketones could trap calcium carbide <em>in-situ</em> to form propargyl alcohols. These serve as ideal leaving groups to complete acetylide transfer after the propargyl alcohols are connected to the desired chemical moieties. Optimization studies revealed benzophenone as the ideal acetylide trap with mild deprotection conditions and low cost. Herein, we reported an effective three-step ethynylation method for various aryl halides by combining the well-established Sonogashira coupling with retro-Favorskii deprotection. Trials of ethynylations for other nucleophilic substrates like aldehydes and nitrones proved ineffective and needed further investigation. The current progress of this method would likely enable future expansion of ethynylation methods of other acetylide acceptors and contribute to synthesis of biomolecules.