Isocyanoalkynes: Leveraging a High-Energy Interstellar Lead for Unique Multi-Bond-Forming Cascades

The reactivity of isocyanoalkynes─alkynes bearing a terminal isocyanide─is an unexplored frontier. The absence of any isocyanoalkyne-based reactions stems from their particularly challenging synthesis, a route originally developed to determine the possible presence of isocyanoacetylene in interstellar gas clouds. The difficult flash-vacuum, pyrolysis-condensation synthesis (240 → -196 °C), the low yield (<10%), and the rapid polymerization of simple isocyanoacetylenes likely dissuaded attempts to investigate the chemistry of these highly energetic molecules. Described here is a robust, scalable synthesis of substituted isocyanoalkynes bearing aromatic, heterocyclic, and aliphatic substituents, and a structural analysis complemented by computations that identify molecular hot spots. These analyses have been particularly important in developing several exploratory reactions that reveal the high reactivity of isocyanoalkynes in unique, multi-bond-forming cascades. The synthesis, structural analyses, and reactivity of isocyanoalkynes provides a robust foundation for exploring, what augurs to be, a versatile new family of nitrogen-substituted alkynes.