Catalytic α–Functionalization of Carboxylic Acid Equivalents and Unprotected Carboxylic Acids

　　arboxylic acid derivatives, such as esters and amides, or carboxylic acids themselves are important structures found in pharmaceuticals and natural products. Therefore, it is important for the more efficient synthesis methods of various functionalized carboxylic acids.
　　Enolate is an important intermediate in the α–functionalization of carbonyl compounds. Enolate, as a nucleophilic agent, is generally used for reactions with electrophilic agents. However, some problems have remained in such classical ionic reactions.
　　Therefore, we have been developing non-classical α–functionalization reactions that take advantage of the properties of each catalyst to complement classical ionic reactions. Nitrenoid-type α–amination and radical-type α–oxidation using copper catalysts, and radical-type α–alkylation using iron catalyst were reported.
 

 
 
　　However, since carboxylic acid equivalents having directing groups are used for efficient enolization in these reactions, the increase in synthesis steps and the limitation of the synthetic scope were issued. In recent years, we have focused on carboxylic acids, which are more ideal building blocks in availability and utility. As a result, we were reported radical-type α–oxidation in the iron/alkali metal cooperative catalytic system.
 

 
 
＜Related Papers＞
1. Keisuke Tokumasu, Ryo Yazaki, Takashi Ohshima
J. Am. Chem. Soc. 2016, 138, 2664–2669. DOI: 10.1021/jacs.5b11773
 
2. Seiya Taninokuchi, Ryo Yazaki, Takashi Ohshima
Org. Lett. 2017, 19, 3187–3190. DOI: 10.1021/acs.orglett.7b01293
 
3. Tsukushi Tanaka, Kayoko Hashiguchi, Takafumi Tanaka, Ryo Yazaki, Takashi Ohshima
ACS Catal. 2018, 8, 8430–8440. DOI: 10.1021/acscatal.8b02361
 
4. Tsukushi Tanaka, Ryo Yazaki, Takashi Ohshima
J. Am. Chem. Soc. 2020, 142, 4517–4524. DOI: 10.1021/jacs.0c00727
 
5. Tsukushi Tanaka, Yunosuke Koga, Yusaku Honda, Akito Tsuruta, Naoya Matsunaga, Satoru Koyanagi, Shigehiro Ohdo, Ryo Yazaki, Takashi Ohshima
Nat. Synth. 2022, in press. DOI: 10.1038/s44160-022-00139-9