Computational Exploration of Dirhodium Complex-Catalyzed Selective Intermolecular Amination of Tertiary vs. Benzylic C-H Bonds

The mechanism and origins of site-selectivity of Rh-2(S-tfpttl)(4)-catalyzed C(sp(3))-H bond aminations were studied using density functional theory (DFT) calculations. The synergistic combination of the dirhodium complex Rh-2(S-tfpttl)(4) with tert-butylphenol sulfamate TBPhsNH(2) composes a pocket that can access both tertiary and benzylic C-H bonds. The nonactivated tertiary C-H bond was selectively aminated in the presence of an electronically activated benzylic C-H bond. Both singlet and triplet energy surfaces were investigated in this study. The computational results suggest that the triplet stepwise pathway is more favorable than the singlet concerted pathway. In the hydrogen atom abstraction by Rh-nitrene species, which is the rate- and site-selectivity-determining step, there is an attractive pi-pi stacking interaction between the phenyl group of the substrate and the phthalimido group of the ligand in the tertiary C-H activation transition structure. By contrast, such attractive interaction is absent in the benzylic C-H amination transition structure. Therefore, the DFT computational results clearly demonstrate how the synergistic combination of the dirhodium complex with sulfamate overrides the intrinsic preference for benzylic C-H amination to achieve the amination of the nonactivated tertiary C-H bond.

Automated summary

The mechanism and origins of the site-selectivity of Rh-2(S-tfpttl)(4)-catalyzed C(sp(3))-H bond aminations were investigated using DFT calculations. The combination of Rh-2(S-tfpttl)(4) and TBPhsNH(2) composed a pocket that could access both tertiary and benzylic C-H bonds, leading to selective amination of the tertiary C-H bond in the presence of an electronically activated benzylic C-H bond. The computational results demonstrated the importance of the triplet stepwise pathway and the attractive pi-pi stacking interaction in achieving the amination of the nonactivated tertiary C-H bond.