Process Development of the Copper(II)-Catalyzed Dehydration of a Chiral Aldoxime and Rational Selection of the Co-Substrate

Nonnhoff J, Gröger H (2021)
ChemistryOpen .

Zeitschriftenaufsatz | E-Veröff. vor dem Druck | Englisch
 
Download
OA 1.84 MB
Abstract / Bemerkung
The access towards chiral nitriles remains crucial in the synthesis of several pharmaceuticals. One approach is based on metal-catalyzed dehydration of chiral aldoximes, which are generated from chiral pool-derived aldehydes as substrates, and the use of a cheap and readily available nitrile as co-substrate and water acceptor. Dehydration of N-acyl alpha-amino aldoximes such as N-Boc-l-prolinal oxime catalyzed by copper(II) acetate provides access to the corresponding N-acyl alpha-amino nitriles, which are substructures of the pharmaceuticals Vildagliptin and Saxagliptin. In this work, a detailed investigation of the formation of the amide as a by-product at higher substrate loadings is performed. The amide formation depends on the electronic properties of the nitrile co-substrate. We could identify an acceptor nitrile which completely suppressed amide formation at high substrate loadings of 0.5 m even when being used with only 2 equivalents. In detail, utilization of trichloroacetonitrile as such an acceptor nitrile enabled the synthesis of N-Boc-cyanopyrrolidine in a high yield of 92% and with full retention of the absolute configuration. © 2021 The Authors. Published by Wiley-VCH GmbH.
Erscheinungsjahr
2021
Zeitschriftentitel
ChemistryOpen
eISSN
2191-1363
Finanzierungs-Informationen
Open-Access-Publikationskosten wurden durch die Universität Bielefeld gefördert.
Page URI
https://pub.uni-bielefeld.de/record/2959873

Zitieren

Nonnhoff J, Gröger H. Process Development of the Copper(II)-Catalyzed Dehydration of a Chiral Aldoxime and Rational Selection of the Co-Substrate. ChemistryOpen . 2021.
Nonnhoff, J., & Gröger, H. (2021). Process Development of the Copper(II)-Catalyzed Dehydration of a Chiral Aldoxime and Rational Selection of the Co-Substrate. ChemistryOpen . https://doi.org/10.1002/open.202100230
Nonnhoff, Jannis, and Gröger, Harald. 2021. “Process Development of the Copper(II)-Catalyzed Dehydration of a Chiral Aldoxime and Rational Selection of the Co-Substrate”. ChemistryOpen .
Nonnhoff, J., and Gröger, H. (2021). Process Development of the Copper(II)-Catalyzed Dehydration of a Chiral Aldoxime and Rational Selection of the Co-Substrate. ChemistryOpen .
Nonnhoff, J., & Gröger, H., 2021. Process Development of the Copper(II)-Catalyzed Dehydration of a Chiral Aldoxime and Rational Selection of the Co-Substrate. ChemistryOpen .
J. Nonnhoff and H. Gröger, “Process Development of the Copper(II)-Catalyzed Dehydration of a Chiral Aldoxime and Rational Selection of the Co-Substrate”, ChemistryOpen , 2021.
Nonnhoff, J., Gröger, H.: Process Development of the Copper(II)-Catalyzed Dehydration of a Chiral Aldoxime and Rational Selection of the Co-Substrate. ChemistryOpen . (2021).
Nonnhoff, Jannis, and Gröger, Harald. “Process Development of the Copper(II)-Catalyzed Dehydration of a Chiral Aldoxime and Rational Selection of the Co-Substrate”. ChemistryOpen (2021).
Alle Dateien verfügbar unter der/den folgenden Lizenz(en):
Creative Commons Namensnennung 4.0 International Public License (CC-BY 4.0):
Volltext(e)
Access Level
OA Open Access
Zuletzt Hochgeladen
2022-01-05T12:56:37Z
MD5 Prüfsumme
bd4e0ebc14e0f4499cb24fd769f71700

Export

Markieren/ Markierung löschen
Markierte Publikationen

Open Data PUB

Web of Science

Dieser Datensatz im Web of Science®
Quellen

PMID: 34889532
PubMed | Europe PMC

Suchen in

Google Scholar