Chemoselective catalytic α -functionalization of carboxylic acid equivalent and carboxylic acid through radical process

Tsukushi Tanaka, Ryo Yazaki, Takashi Ohshima

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)417-426
Number of pages10
JournalYuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry
Issue number5
Publication statusPublished - May 1 2021

All Science Journal Classification (ASJC) codes

  • Organic Chemistry


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