Nickel(II)-Catalyzed [5 + 1] Annulation of 2‑Carbonyl-1-propargylindoles with Hydroxylamine To Synthesize Pyrazino[1,2‑a]indole-2-oxides in Water

An atom-economical and practical method for the efficient synthesis of various pyrazino­[1,2-a]­indole-2-oxides was developed through a nickel­(II)-catalyzed [5 + 1] annulation of 2-carbonyl-1-propargylindoles with hydroxylamine in water without using an organic solvent. The reaction involved an initial condensation of 2-carbonyl-1-propargylindoles with hydroxylamine to afford oxime intermediates, which then underwent a nickel­(II)-catalyzed 6-exo-dig cyclization. Preliminary studies showed that (n-Bu)4NI served as a phase transfer catalyst and promoted the formation of active nickel­(II) species. More importantly, the nickel­(II) salt and phase transfer catalyst-in-water could be recycled seven times, and a gram scalable product was easily obtained in good yields through a filtration and washing protocol.