Radical Amination of C(sp3)–H Bonds Using N‑Hydroxyphthalimide and Dialkyl Azodicarboxylate

• Published in: Journal of organic chemistry Vol. 77; no. 22; pp. 9959 - 9969
• Main Authors: Amaoka, Yuuki, Kamijo, Shin, Hoshikawa, Tamaki, Inoue, Masayuki
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 16.11.2012; Amer Chemical Soc
• Subjects: Aliphatic compounds; Alkanes - chemistry; Amination; Azo Compounds - chemistry; Catalysis; Chemistry; Chemistry, Organic; Exact sciences and technology; Free radicals chemistry; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Hydrogen Bonding; Molecular Structure; Nitrogen - chemistry; Noncondensed benzenic compounds; Organic chemistry; Phthalimides - chemistry; Physical Sciences; Preparations and properties; Reactivity and mechanisms; Science & Technology; Stereoisomerism; OXIDATION; FUNCTIONALIZATION; BENZYLIC POSITIONS; ACTIVATION; INTERMOLECULAR AMINATION; HYDROCARBONS; HYPERVALENT SULFONYLIMINO-LAMBDA-BROMANE; C-H AMINATION; CATALYSTS; MOLECULAR-OXYGEN; Stoichiometry; Catalytic reaction; Nitroxyl; Acetylenic compound; Carbon-hydrogen bond; Chemoselectivity; Aliphatic compound; Chemical bond; Propargylic compound; Natural compound; Organic carbamate; Imide; Trapping; Amine; Amination; Functionalization; Benzylic compound; Organic free radical; Hydrazine
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo301840e

A direct conversion of C(sp3)–H bonds to C(sp3)–N bonds has been achieved by utilizing catalytic N-hydroxyphthalimide (NHPI) and stoichiometric dialkyl azodicarboxylate. NHPI functions as a precursor of the electron-deficient phthalimide N-oxyl radical (PINO) to abstract hydrogens, and dialkyl azodicarboxylate acts as a trapping agent of the resultant carbon radical to generate the hydrazine derivatives. This C–H amination proceeds in a highly chemoselective manner with a wide applicability to functionalize benzylic, propargylic, and aliphatic C–H bonds. Furthermore, the obtained hydrazine compounds were readily converted to the corresponding carbamates or amines. Hence, the present protocol for direct introduction of the nitrogen functionality serves as a powerful tool for efficient construction of nitrogen-substituted natural products and pharmaceuticals.