Catalytic Intermolecular C(sp3)–H Amination: Selective Functionalization of Tertiary C–H Bonds vs Activated Benzylic C–H Bonds

• Published in: Journal of the American Chemical Society Vol. 143; no. 17; pp. 6407 - 6412
• Main Authors: Brunard, Erwan, Boquet, Vincent, Van Elslande, Elsa, Saget, Tanguy, Dauban, Philippe
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 05.05.2021; Amer Chemical Soc
• Subjects: Catalysis; Chemical Sciences; Chemistry; Chemistry, Multidisciplinary; Organic chemistry; Physical Sciences; Science & Technology; OXIDATION; NITRENE TRANSFER-REACTIONS; STEREOSELECTIVE FUNCTIONALIZATION; CHALLENGES
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.1c03872

A catalytic intermolecular amination of nonactivated tertiary C­(sp3)–H bonds (BDE of 96 kcal·mol–1) is reported for substrates displaying an activated benzylic site (BDE of 85 kcal·mol–1). The tertiary C­(sp3)–H bond is selectively functionalized to afford α,α,α-trisubstituted amides in high yields. This unusual site-selectivity results from the synergistic combination of Rh2(S-tfpttl)4, a rhodium­(II) complex with a well-defined catalytic pocket, with tert-butylphenol sulfamate (TBPhsNH2), which leads to a discriminating rhodium-bound nitrene species under mild oxidative conditions. This catalytic system is very robust, and the reaction was performed on a 50 mmol scale with only 0.01 mol % of catalyst. The TBPhs group can be removed under mild conditions to afford the corresponding NH-free amines.