Reaction with N-Unprotected Ketimines

　　α,α-disubstituted amino acids are important compounds for pharmaceutical science. The nucleophilic addition to ketimines is one of the synthetic methods for these compounds. Many reactions with N-protected ketimines have been reported. However, these processes are not environmentally friendly for the deprotection process. We are interested in the reactions with N-unprotected ketimines, which directly give N-unprotected amines. These processes are environmentally friendly as they do not require deprotection (Scheme 1).
 

 
 
　　We also developed new methods for the synthesis of N-unprotected ketimines (Scheme 2). A variety of N-unprotected ketimines which were difficult to synthesize by conventional methods can be easily accessed, greatly expanding the utility of N-unprotected ketimines. By applying these reactions to one-pot reactions, we also achieved synthetic routes without the isolation process of N-unprotected ketimines.
 

 
 
＜Related Papers＞
Addition to N-Unprotected Ketimines
1. Kazuhiro Morisaki, Hiroyuki Morimoto, Takashi Ohshima
Chem. Commun. 2017, 53, 6319–6322. DOI: 10.1039/C7CC02194A
 
2. Masanao Sawa, Kazuhiro Morisaki, Yuta Kondo, Hiroyuki Morimoto, Takashi Ohshima
Chem. Eur. J. 2017, 23, 17022–17028. DOI: 10.1002/chem.201703516
 
3. Ryohei Yonesaki, Yuta Kondo, Walaa Akkad, Masanao Sawa, Kazuhiro Morisaki, Hiroyuki Morimoto, Takashi Ohshima
Chem. Eur. J. 2018, 24, 15211–15214. DOI: 10.1002/chem.201804078
 
4. Masanao Sawa, Shotaro Miyazaki, Ryohei Yonesaki, Hiroyuki Morimoto, Takashi Ohshima
Org. Lett. 2018, 20, 5393–5397. DOI: 10.1021/acs.orglett.8b02306
 
5. Ryohei Yonesaki, Ibuki Kusagawa, Hiroyuki Morimoto, Tamio Hayashi, Takashi Ohshima
Chem. Asian. J. 2020, 15, 499–502. DOI: 10.1002/asia.201901745
 
6. Tetsuya Kadota, Masanao Sawa, Yuta Kondo, Hiroyuki Morimoto, Takashi Ohshima
Org. Lett. 2021, 23, 4553–4558. DOI: 10.1021/acs.orglett.1c01194
 
7. Koki Yamada, Yuta Kondo, Akihiko Kitamura, Tetsuya Kadota, Hiroyuki Morimoto, Takashi Ohshima
ACS Catal. 2023, 13, 3158–3163. DOI: 10.1021/acscatal.2c05953
 
 
Direct Catalytic Synthesis of N-Unprotected Ketimines
1. Yuta Kondo, Kazuhiro Morisaki, Yoshinobu Hirazawa, Hiroyuki Morimoto, Takashi Ohshima
Org. Process Res. Dev. 2019, 23, 1718–1724. DOI: 10.1021/acs.oprd.9b00226
 
2. Yuta Kondo, Tetsuya Kadota, Yoshinobu Hirazawa, Kazuhiro Morisaki, Hiroyuki Morimoto, Takashi Ohshima
Org. Lett. 2020, 22, 120–125. DOI: 10.1021/acs.orglett.9b04038
 
3. Yuta Kondo, Yoshinobu Hirazawa, Tetsuya Kadota, Koki Yamada, Kazuhiro Morisaki, Hiroyuki Morimoto, Takashi Ohshima
Org. Lett. 2022,  24, 6594–6598. DOI: 10.1021/acs.orglett.2c02587