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

A catalytic intermolecular amination of nonactivated tertiary C(sp 3 )-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(sp 3 )-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 Rh 2 ( S -tfpttl) 4 , a rhodium(II) complex with a well-defined catalytic pocket, with er -butylphenol sulfamate (TBPhsNH 2 ), 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.