Bioinspired Radical-Mediated Transition-Metal-Free Synthesis of N-Heterocycles under Visible Light

A redox-active iminoquinone motif connected with pi-delocalized pyrene core has been reported that can perform efficient two-electron oxidation of a class of substrates. The design of the molecule was inspired by the organic redox cofactor topaquinone (TPQ), which executes amine oxidation in the enzyme, copper amine oxidase. Easy oxidation of both primary and secondary alcohols happened in the presence of catalytic KOtBu, which could reduce the ligand backbone to its iminosemiquinonate form under photoinduced conditions. Moreover, this easy oxidation of alcohols under aerobic condition could be elegantly extended to multi-component, one-pot coupling for the synthesis of quinoline and pyrimidine. This organocatalytic approach is very mild (70 degrees C, 8 h) compared to a multitude of transition-metal catalysts that have been used to prepare these heterocycles. A detailed mechanistic study proves the intermediacy of the iminosemiquinonate-type radical and a critical hydrogen atom transfer step to be involved in the dehydrogenation reaction.

Automated summary

This study reports a redox-active iminoquinone motif connected with a pi-delocalized pyrene core, capable of efficiently performing two-electron oxidation of a class of substrates. Inspired by the organic redox cofactor topaquinone (TPQ) in the enzyme copper amine oxidase, the molecule can easily oxidize primary and secondary alcohols in the presence of catalytic KOtBu. Under photoinduced conditions, the ligand backbone can be reduced to its iminosemiquinonate form, allowing for multi-component, one-pot coupling for the synthesis of quinoline and pyrimidine.