Simple and Efficient Aromatic C–H Oxazolination

• Published in: Precision Chemistry Vol. 1; no. 5; pp. 316 - 325
• Main Authors: Shi, Qiu, Huang, Yu, Liu, Wenbo H.
• Format: Journal Article
• Language: English
• Published: University of Science and Technology of China and American Chemical Society 24.07.2023; American Chemical Society
• Subjects: aromatic C−H functionalization; oxazolines; aromatic electrophilic substitution; late-stage functionalization; metal free
• ISSN: 2771-9316; 2771-9316
• DOI: 10.1021/prechem.3c00035

Aromatic oxazolines are versatile in organic synthesis as directing groups, ligands, and protected carboxylic acids. Developing efficient approaches to oxazoline from an aromatic C–H bond is more desirable compared to the established protocols from carboxylic acid and its equivalents. Herein, a simple and efficient aromatic C–H oxazolination with broad substrate scope is described. By employing this transformation as an enabling step, diversity-oriented synthesis of functionalized arenes and target-oriented synthesis of four drugs were accomplished. Mechanistic experiments suggest that this aromatic oxazolination is an electrophilic aromatic substitution. It is anticipated that this transformation will find applications in aromatic C–H functionalization with oxazoline either as a removable directing group or as a masked carboxylic acid.