Late‐Stage Functionalization of Arylacetic Acids by Photoredox‐Catalyzed Decarboxylative Carbon–Heteroatom Bond Formation

• Published in: Chemistry : a European journal 2018-07, Vol.24 (37), p.9254-9258
• Main Authors: Sakakibara, Yota, Ito, Eri, Fukushima, Tomohiro, Murakami, Kei, Itami, Kenichiro
• Format: Article
• Language: English
• Subjects: Acids; Agrochemicals; arylacetic acids; Bioactive compounds; Biocompatibility; Biological activity; Bonding; Carbon; Chemistry; Chlorine; Coupling (molecular); Decarboxylation; Drugs; Functional groups; imidation; Molecular chains; Natural products; Nitrogen; Organic chemistry; Oxygen; Pharmaceuticals; photoredox catalysts; ruthenium
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201802143

The rapid transformation of pharmaceuticals and agrochemicals enables access to unexplored chemical space and thus has accelerated the discovery of novel bioactive molecules. Because arylacetic acids are regarded as key structures in bioactive compounds, new transformations of these structures could contribute to drug/agrochemical discovery and chemical biology. This work reports carbon–nitrogen and carbon–oxygen bond formation through the photoredox‐catalyzed decarboxylation of arylacetic acids. The reaction shows good functional group compatibility without pre‐activation of the nitrogen‐ or oxygen‐based coupling partners. Under similar reaction conditions, carbon–chlorine bond formation was also feasible. This efficient derivatization of arylacetic acids makes it possible to synthesize pharmaceutical analogues and bioconjugates of pharmaceuticals and natural products. Decarboxylative functionalization: Carbon–nitrogen, carbon–oxygen, and carbon–chlorine bond formation through photoredox‐catalyzed decarboxylation of arylacetic acids is reported. The reaction shows good functional group compatibility without pre‐activation of a nitrogen‐ or oxygen‐based coupling partner. This efficient derivatization of arylacetic acids allows for the synthesis of pharmaceutical analogs and bioconjugates of pharmaceuticals and natural products (see scheme).