We report a new copper-catalyzed [2 + 2 + 1] annulation process through the selective cleavage of sigma and triple C-C and C-H bonds using two ynone units. This new methodology involves breaking multiple chemical bonds in a single operation, including C≡C, C-C, C-H, and N-O. These high-value adducts lead to a diverse collection of synthetically challenging trisubstituted indolizines by the simultaneous engagement of different bond-breaking events and show excellent fluorescence in green aqueous solutions.