Stereoretentive N-Arylation of Amino Acid Esters with Cyclohexanones Utilizing a Continuous-Flow System.

Tomohiro Ichitsuka, Shingo Komatsuzaki, Koichiro Masuda, Nagatoshi Koumura, Kazuhiko Sato, Shū Kobayashi

Chemistry (Weinheim an der Bergstrasse, Germany) 2021 Jul 26

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The N-arylation of chiral amino acid esters with minimal racemization is a challenging transformation because of the sensitivity of the α-stereocenter. A versatile synthetic method was developed to prepare N-arylated amino acid esters using cyclohexanones as aryl sources under continuous-flow conditions. The designed flow system, which consists of a coil reactor and a packed-bed reactor containing a Pd(OH)2 /C catalyst, efficiently afforded the desired N-arylated amino acids without significant racemization, accompanied by only small amounts of easily removable co-products (i. e., H2 O and alkanes). The efficiency and robustness of this method allowed for the continuous synthesis of the desired product in very high yield and enantiopurity with high space-time yield (74.1 g L-1 h-1 ) and turnover frequency (5.9 h-1 ) for at least 3 days. © 2021 Wiley-VCH GmbH.

Citation

Tomohiro Ichitsuka, Shingo Komatsuzaki, Koichiro Masuda, Nagatoshi Koumura, Kazuhiko Sato, Shū Kobayashi. Stereoretentive N-Arylation of Amino Acid Esters with Cyclohexanones Utilizing a Continuous-Flow System. Chemistry (Weinheim an der Bergstrasse, Germany). 2021 Jul 26;27(42):10844-10848