On the Mechanism of Ligand-Assisted, Copper-Catalyzed Benzylic Amination by Chloramine-T

The mechanism of hydrocarbon amination by chloramine-T derivatives catalyzed by (diimine)copper complexes has been investigated. The initial synthetic study of the reactions revealed ligand-accelerated catalysis, significant sensitivity to the electronic character of the substrates, and low to moderate enantioselectivities with homochiral ligands. Various mechanistic probes, both experimental and computational, have been focused on the C−H insertion process. A kinetic isotope effect of 4.6 was found in the amination of α-D(H)-cumenes catalyzed by [(diimine)Cu(solv)]Z. Amination of the isomeric substrates cis - and trans -4- tert -butyl-1-phenylcyclohexanes with 4-Me-C 6 H 4 SO 2 NNaCl (chloramine-T) or 4-NO 2 -C 6 H 4 SO 2 NNaCl (chloramine-N) catalyzed by [(diimine)Cu(CH 3 CN)]PF 6 produced in all cases an approximately 1:1 mixture of the corresponding cis - and trans -4- tert -butyl-1-phenyl-1-sulfonaminocyclohexanes. Amination of the radical-clock substrate 1-phenyl-2-benzylcyclopropane with chloramine-T/(diimine)Cu(CH 3 CN)]PF 6 gave a mixture of ring-opened and cyclopropylmethylamino derivatives. Together, these results are most consistent with a stepwise insertion of an N-Ts(Ns) unit into the C−H bond, via carbon radicals, and a secondary contribution from a concerted insertion pathway. B3LYP and CASSCF computations suggest that the C−H insertion step involves the reaction of the hydrocarbon with a Cu-imido (nitrene) complex, [(diimine)Cu═NSO 2 R] + . The ground-state triplet of the Cu-imido complex is calculated to be 3−13 kcal/mol more stable that the singlet complex, depending on the method and basis sets employed. The reaction of each complex with toluene is modeled to find that the C−H insertion transition state for the triplet (Δ G ‡ = 8.2 kcal/mol) is lower in energy than the singlet. The former reacts by a stepwise H-atom abstraction, while the latter reacts by a concerted C−H insertion. These results and kinetic isotope effect calculations for the singlet (2.9) and triplet (4.8) pathways, respectively, agree with the experimental observations (4.6) and point to a major role for the triplet complex in the stepwise, nonstereoselective insertion pathway.