Oxidative Fluorination of Cyclopropylamides through Organic Photoredox Catalysis

• Published in: Angewandte Chemie International Edition Vol. 59; no. 38; pp. 16420 - 16424
• Main Authors: Wang, Ming‐Ming, Waser, Jérôme
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 14-09-2020
• Edition: International ed. in English
• Subjects: Amines; aminocyclopropanes; Benzophenone; Catalysis; Catalysts; Fluorination; Fluorine; Imines; photocatalysis; Photoredox catalysis; ring-opening; Ultraviolet radiation; fluorination; ring-opening; benzophenone; photocatalysis; aminocyclopropanes
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202007864

We report an oxidative ring‐opening strategy to transform cyclopropylamides and cyclobutylamides into fluorinated imines. The imines can be isolated in their more stable hemiaminal form, with the fluorine atom installed selectively at the γ or δ position. Both inexpensive benzophenone with UVA light or organic and inorganic dyes with blue light could be used as photoredox catalysts to promote this process. Various fluorinated amines were then obtained by nucleophilic attack on the hemiaminals in one pot, giving access to a broad range of useful building blocks for medicinal chemistry.
Make it shine: We report a photocatalyzed ring‐opening fluorination of cyclopropylamides and cyclobutylamides. Both cheap benzophenone with UVA light or organic and inorganic dyes with blue light could be used to promote this process. Various fluorinated amines were obtained through nucleophilic attack on the formed hemiaminals in one pot, giving access to a broad range of useful building blocks for medicinal chemistry.