Phenols are important building blocks in organic synthesis and are often found, e.g., in natural products, pharmaceutically active molecules, or materials. Phenols can be synthesized from different types of aryl precursors. Benzoic acid derivatives could be particularly useful as precursors because they are stable and readily available, and their conversion to phenols does not require directing groups. However, transforming benzoic acids to phenols can be challenging due to the high energy barrier of decarboxylation and often requires, e.g., high temperatures.
Wenbo H. Liu, Sun Yat-Sen University, Guangzhou, China, and colleagues have developed a practical approach for the preparation of phenols from benzoic acids under mild conditions. The team reacted a wide range of benzoic acid derivatives with meta-chloroperoxybenzoic acid (m-CPBA). The resulting peroxy derivatives were then reacted with triflic acid (F3CSO3H or TfOH), leading to an acid-induced migration that forms the desired Caryl–O bond. Finally, the desired phenol products were obtained by methanolysis.
The reactions were performed at room temperature and showed a broad substrate scope. The desired phenols were obtained in generally high yields. The approach can also be used with cinnamic acids, giving vinyl esters. The researchers propose that the mechanism of the migration step involves a free carbocation. According to the team, the easily accessible substrates, simple reagents, and the importance of phenol products indicate that the approach could have broad applications in organic synthesis.
- Simple and Practical Conversion of Benzoic Acids to Phenols at Room Temperature,
Wenzhang Xiong, Qiu Shi, Wenbo H. Liu,
J. Am. Chem. Soc. 2022.