Enolization of carboxylic acid derivatives is the central science of fundamental carbonyl chemistry. The catalytic methods to activate carboxylic acid remained unexplored due to the intrinsic low acidity of α -protons, although enormous examples of catalytic activation (enolization) method for aldehydes, ketones, and ester derivatives have been reported. The innate Brønsted acidic carboxylic acid functionality also disrupts the deprotonation of α -protons. Therefore, more than two equivalents of a strong base such as lithium diisopropylamide are required for efficient enolization, which makes chemoselective enolization of carboxylic acid over more acidic carbonyls a formidable task. Furthermore, recent enolization methods were only applied to redox-neutral coupling using 2e - electrophiles and catalytic α -functionalization of carboxylic acids through a 1e - radical process, which could complement the chemoselectivity, and functional group tolerance restricted in the classical 2e - ion reaction, has never been achieved. Herein, we developed chemoselective catalytic activation of carboxylic acid equivalent, acylpyrazole, and carboxylic acid for a 1e - radical process without external addition of stoichiometric amounts of Brønsted base. The present chemoselective catalysis could be applied to late-stage α - amination and oxidation, allowing for concise access to highly versatile unnatural α -amino acid and hydroxy acid derivatives. Moreover, chemoselective α -functionalization of less reactive carboxylic acids was achieved over innately more reactive carbonyl functionalities.
|Number of pages||10|
|Journal||Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry|
|Publication status||Published - May 1 2021|
All Science Journal Classification (ASJC) codes
- Organic Chemistry