Asymmetric Synthesis of 4,4-(Difluoro)glutamic Acid via Chiral Ni(II)-Complexes of Dehydroalanine Schiff Bases. Effect of the Chiral Ligands Structure on the Stereochemical Outcome

Yoshinori Tokairin; Yuhei Shigeno; Jianlin Han; Gerd-Volker Röschenthaler; Hiroyuki Konno; Hiroki Moriwaki; Vadim A Soloshonok

doi:10.1002/open.201900343

Asymmetric Synthesis of 4,4-(Difluoro)glutamic Acid via Chiral Ni(II)-Complexes of Dehydroalanine Schiff Bases. Effect of the Chiral Ligands Structure on the Stereochemical Outcome

ChemistryOpen. 2020 Jan 29;9(1):93-96. doi: 10.1002/open.201900343. eCollection 2020 Jan.

Authors

Yoshinori Tokairin¹, Yuhei Shigeno², Jianlin Han³, Gerd-Volker Röschenthaler¹, Hiroyuki Konno², Hiroki Moriwaki⁴, Vadim A Soloshonok^{5

6}

Affiliations

¹ Department of Life Sciences and Chemistry, Jacobs University Bremen GmbH, Campus Ring 1, 28759, Bremen, Germany.
² Department of Biochemical Engineering, Graduate School of Science and Technology, Yamagata University, Yonezawa, Yamagata, 992-8510, Japan.
³ College of Chemical Engineering, Nanjing Forestry University, Nanjing, 210037, China.
⁴ Hamari Chemicals Ltd., 1-4-29 Kunijima, Higashi-Yodogawa-ku, Osaka, 533-0024, Japan.
⁵ Department of Organic Chemistry I, Faculty of Chemistry, University of the Basque Country UPV/EHU, Paseo Manuel Lardizábal 3, 20018, San Sebastián, Spain.
⁶ IKERBASQUE, Basque Foundation for Science, María Díaz de Haro 3, Plaza Bizkaia, 48013, Bilbao, Spain.

Abstract

Four differently substituted chiral Ni(II)-complexes of dehydroalanine Schiff base were prepared and reacted with BrCF₂COOEt/Cu under the standard reaction conditions. The observed diastereoselectivity was found to depend on the degree and pattern of chlorine substitution for hydrogen in the structure of the dehydroalanine complexes. The unsubstituted complex gave the ratio of diastereomers (S)(2S)/(S)(2R) of 66/34. On the other hand, introduction of chlorine atoms in the strategic positions on the chiral ligands allowed to achieve a practically attractive diastereoselectivity of (∼98.5/1.5). Diastereomerically pure major product was disassembled to prepare 9-fluorenylmethyloxycarbonyl (Fmoc) derivative of (S)-4,4-difluoroglutamic acid.

Keywords: Ni(II)-complexes; Schiff bases; asymmetric synthesis; fluorine; tailor-made amino acids.

Publication types

Research Support, Non-U.S. Gov't