Site‐Selective Decarboxylative Direct Formylation of Nitrogen Heterocycles (Azaindoles, Indoles, Pyrroles) and Anilines Utilizing Glyoxylic Acid

• Published in: Advanced synthesis & catalysis Vol. 365; no. 8; pp. 1238 - 1246
• Main Authors: Laha, Joydev K., Hunjan, Mandeep Kaur, Maity, Tapas, Hazra, Amitava
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 25.04.2023; Wiley Subscription Services, Inc
• Subjects: aldehydes; Aniline; azaindoles; Chemistry; Chemistry, Applied; Chemistry, Organic; decarboxylative formylation; formylation; Glyoxylic acid; Indoles; K2S2O8; Natural products; Nitrogen; Physical Sciences; Potassium persulfate; Pyrroles; Reagents; Science & Technology; METHANOL; HEXAMETHYLENETETRAMINE; formylation; glyoxylic acid; ACYLATION; LIGHT; N-FORMYLATION; CATALYST; K2S2O8; C3-FORMYLATION; decarboxylative formylation; aldehydes; AMINES; CHEMISTRY; azaindoles
• ISSN: 1615-4150; 1615-4169
• DOI: 10.1002/adsc.202201384

A new method for formylation of nitrogen heterocycles overcoming the limitations of classical approaches using a cheap feedstock formylating agent especially under mild and neutral conditions is the subject of this current investigation. This work describes direct formylation of nitrogen heterocycles (azaindoles, indoles, pyrroles) and anilines using glyoxylic acid as the formyl source and K2S2O8 as the exclusive reagent. The key features include a general method for both C‐ and N‐formylation under neutral and mild reaction conditions. The application of the method is further demonstrated in the tandem synthesis of nitrogen heterocycles, pharmaceuticals, and a natural product. Unlike aroylation with arylglyoxylic acids, a previously unknown pathway for the direct formylation with glyoxylic acid in the presence of K2S2O8 is now unveiled.