Direct Deamination of Primary Amines via Isodiazene Intermediates

• Published in: Journal of the American Chemical Society Vol. 143; no. 42; pp. 17366 - 17373
• Main Authors: Berger, Kathleen J, Driscoll, Julia L, Yuan, Mingbin, Dherange, Balu D, Gutierrez, Osvaldo, Levin, Mark D
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 27.10.2021
• Subjects: Alkanes - chemical synthesis; Amines - chemistry; Aniline Compounds - chemistry; Deamination; Imines - chemistry; Models, Chemical
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.1c09779

We report here a reaction that selectively deaminates primary amines and anilines under mild conditions and with remarkable functional group tolerance including a range of pharmaceutical compounds, amino acids, amino sugars, and natural products. An anomeric amide reagent is uniquely capable of facilitating the reaction through the intermediacy of an unprecedented monosubstituted isodiazene intermediate. In addition to dramatically simplifying deamination compared to existing protocols, our approach enables strategic applications of iminium and amine-directed chemistries as traceless methods. Mechanistic and computational studies support the intermedicacy of a primary isodiazene which exhibits an unexpected divergence from previously studied secondary isodiazenes, leading to cage-escaping, free radical species that engage in a chain, hydrogen-atom transfer process involving aliphatic and diazenyl radical intermediates.