Synthesis of α‑Aminonitriles via Ammonium-Catalyzed Reactions of Aminoacetonitrile
α-Aminonitriles are not only broadly useful building blocks but also structural motifs in bioactive molecules. The Strecker reaction is one of the most widely used methods for α-aminonitrile synthesis. However, a severe drawback in Strecker reactions is the required use of a stoichiometric amount of...
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Veröffentlicht in: | Journal of the American Chemical Society 2024-09, Vol.146 (38), p.25934-25942 |
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Hauptverfasser: | , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | α-Aminonitriles are not only broadly useful building blocks but also structural motifs in bioactive molecules. The Strecker reaction is one of the most widely used methods for α-aminonitrile synthesis. However, a severe drawback in Strecker reactions is the required use of a stoichiometric amount of toxic cyanation reagents. Thus, the development of a greener and widely applicable method for the synthesis of aminonitriles from readily available starting materials presents an important yet unmet challenge. We developed a general and new method for the synthesis of aminonitriles from readily available aminoacetonitrile. This method utilized off-the-shelf ammonium salts as catalysts, tolerated air and moisture, and avoided the use of cyanation reagents, which rendered it a greener alternative to the widely practiced Strecker reaction approach. We further illustrated that chiral ammonium-catalyzed asymmetric reactions of N-arylidene aminoacetonitriles could provide chiral α-tertiary and α-quaternary aminonitriles and α-aminonitriles bearing two continuous stereocenters. |
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ISSN: | 0002-7863 1520-5126 1520-5126 |
DOI: | 10.1021/jacs.4c09789 |