- 著者
-
田中 津久志
矢崎 亮
大嶋 孝志
- 出版者
- 公益社団法人 有機合成化学協会
- 雑誌
- 有機合成化学協会誌 (ISSN:00379980)
- 巻号頁・発行日
- vol.79, no.5, pp.417-426, 2021-05-01 (Released:2021-05-11)
- 参考文献数
- 72
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, acylpyra-zole, 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.