Selective Hydrolysis of Primary and Secondary Amides Enabled by Visible Light

Abstract

Amide hydrolysis is a fundamentally important transformation in organic chemistry. Developing hydrolysis procedures under mild conditions with a broad substrate scope is desirable. Herein, by leveraging a photoresponsive auxiliary o-nitroanilide, we established a mild two-step protocol for the hydrolysis of primary and secondary amides. This protocol is driven by visible light irradiation at room temperature under neutral conditions, which tolerates numerous acid- and base-sensitive functional groups. Various drugs, natural product-, and amino acid-derived amides can be selectively hydrolyzed.

Ring Opening of N-Acyl Lactams Using Nickel-Catalyzed Transamidation

“…In the recent literature, there have been notable publications that focus on reactions with amides used as starting materials to facilitate the conversion of diverse carbonyl compounds, including other amide functional groups . This strategic approach involves the introduction of new substituents by inducing the dissociation of carbon–nitrogen bonds in amides through the manipulation of the steric and electronic attributes of the amide skeleton, thereby leading to the perturbation of their resonance stability . While investigations into methods involving transition metal catalysts are ongoing, interesting findings pertaining to reactions conducted without transition metal catalysts have also been reported …”