One-Pot Synthesis of Quinoxaline N-Oxides via Radical-Mediated Cyclization of Ketene N,S-Acetals

A facile and efficient one-pot synthesis of bench-stable quinoxaline N-oxides has been realized using a-oxoketene N,S-acetals and tert-butyl nitrite (TBN) in open air via cascade annulation. The double functionalization of N,S-acetals proceeds through an unanticipated (Csp(2))-H nitrosation by NO radical (generated in situ by TBN) and subsequent intramolecular N-arylation leading to quinoxaline, which undergoes oxidation to quinoxaline N-oxides harboring three variegated substituents on their framework. Notably, two new C-N bonds are formed with the same N-oxide nitrogen. This protocol features short reaction time, good functional group tolerance and mild conditions, and does not require the use of either catalyst or external additive.

Automated summary

A one-pot synthesis of bench-stable quinoxaline N-oxides was achieved using a-oxoketene N,S-acetals and tert-butyl nitrite in open air. The double functionalization of N,S-acetals proceeds via an unexpected (Csp(2))-H nitrosation by NO radical and subsequent intramolecular N-arylation leading to quinoxaline, which is then oxidized to quinoxaline N-oxides. This protocol offers short reaction time, good functional group tolerance, and mild conditions without the need for a catalyst or external additive.