Open AccessDirect Deamination of Primary Amines via Isodiazene Intermediates
Author(s) -
Kathleen J. Berger,
Julia L. Driscoll,
Mingbin Yuan,
Balu D. Dherange,
Osvaldo Gutiérrez,
Mark D. Levin
Publication year - 2021
Publication title -
journal of the american chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.115
H-Index - 612
eISSN - 1520-5126
pISSN - 0002-7863
DOI - 10.1021/jacs.1c09779
Subject(s) - chemistry , primary (astronomy) , iminium , deamination , amine gas treating , amide , reactive intermediate , reagent , combinatorial chemistry , organic chemistry , catalysis , enzyme , physics , astronomy
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.