Tuesday, 29 January 2019

Large scale synthesis of chiral (3Z,5Z)-2,7-dihydro-1H-azepine-derived Hamari ligand for general asymmetric synthesis of tailor-made amino acids.

str3 str4
(R)-2,2′-bis(bromomethyl)-1,1′-binaphthalene ((R)-17) was prepared in the identical manner and had identical analytical properties to those given here.
1H NMR (400 MHz, CDCl3): δ 4.25 (4H, s, 2 × CH2), 7.07 (2H, dd, J = 8.4, 0.8 Hz, ArH), 7.27 (2H, ddd, J = 8.4, 6.8, 1.2 Hz, ArH), 7.48 (2H, ddd, J = 8.2, 6.8, 1.2 Hz, ArH), 7.74 (2H, d, J = 8.6 Hz, ArH), 7.92 (2H, d, J = 8.2 Hz, ArH), 8.02 (2H, d, J = 8.6 Hz, ArH).
13C NMR (100.6 MHz, CDCl3): δ 32.6 (CH2), 126.80 (ArCH), 126.82 (ArCH), 126.84 (ArCH), 127.7 (ArCH), 128.0 (ArCH), 129.4 (ArCH), 132.5 (quaternary ArC), 133.3 (quaternary ArC), 134.1 (quaternary ArC), 134.2 (quaternary ArC).
[α]20D = +173.8° (c = 1.0, CHCl3).

Abstract Image
An advanced process for large scale (500 g) preparation of a (3Z,5Z)-2,7-dihydro-1H-azepine-derived chiral tridentate ligand (Hamari ligand), widely used for asymmetric synthesis of tailor-made α-amino acids via the corresponding glycine Schiff base Ni(II) complex, is disclosed. The process includes amidation, bis-alkylation, and precipitation/purification of the target compound by TFA as a counterion.
Large Scale Synthesis of Chiral (3Z,5Z)-2,7-Dihydro-1H-azepine-Derived Hamari Ligand for General Asymmetric Synthesis of Tailor-Made Amino Acids
 Hamari Chemicals Ltd., 1-4-29 Kunijima, Higashi-Yodogawa-ku, Osaka 533-0024, Japan
 Hamari Chemicals USA, San Diego Research Center11494 Sorrento Valley Road, San Diego, California 92121, United States
§ Department of Organic Chemistry I, Faculty of ChemistryUniversity of the Basque Country UPV/EHUPaseo Manuel Lardizábal 3, 20018 San Sebastián, Spain
 IKERBASQUE, Basque Foundation for ScienceMaría Díaz de Haro 3, Plaza Bizkaia, 48013 Bilbao, Spain
Org. Process Res. Dev., Article ASAP
DOI: 10.1021/acs.oprd.8b00406
Publication Date (Web): January 18, 2019
Copyright © 2019 American Chemical Society
This article is part of the Japanese Society for Process Chemistry special issue.