Direct Deamination of Primary Amines via Isodiazene Intermediates

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.

Automated summary

The study reports a reaction that selectively deaminates primary amines and anilines under mild conditions with remarkable functional group tolerance, including pharmaceutical compounds, amino acids, amino sugars, and natural products. An anomeric amide reagent facilitates the reaction through the intermediacy of an unprecedented monosubstituted isodiazene intermediate, simplifying deamination and enabling strategic applications of iminium and amine-directed chemistries as traceless methods. Mechanistic and computational studies support the intermedicacy of a primary isodiazene, which exhibits unexpected divergence from previously studied secondary isodiazenes, leading to cage-escaping, free radical species undergoing a chain hydrogen-atom transfer process with aliphatic and diazenyl radical intermediates.