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 alpha, alpha, alpha-trisubstituted amides in high yields. This unusual site-selectivity results from the synergistic combination of Rh-2(Stfpttl)(4), a rhodium(II) complex with a well-defined catalytic pocket, with tert-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.