Ynamides as Three-Atom Components in Cycloadditions: An Unexplored Chemical Reaction Space.

While 1,3-dipolar cycloadditions have appeared to be a fertile area for research, as attested by the numerous synthetic transformations and resulting applications that have been developed during the past 60 years, the use of neutral three-atom components (TACs) in (3+2) cycloadditions remains comparatively sparse. Neutral TACs, however, have great synthetic potential given that their reaction with a π system can produce zwitterionic cycloadducts that may be manipulated for further chemistry. We report herein that ynamides, a class of carbon π systems that has seen wide interest over the last two decades, can be used as neutral TACs in thermally induced intramolecular (3+2) cycloaddition reactions with alkynes to yield a variety of functionalized pyrroles. The transformation is proposed to occur in a stepwise manner via the intermediacy of a pyrrolium ylide, from which the electron-withdrawing group on the nitrogen atom undergoes an intramolecular 1,2-shift to produce the neutral pyrrole. This work demonstrates a yet unexplored facet of ynamide reactivity with great potential in heterocyclic chemistry.