Facile Amine Formation by Intermolecular Catalytic Amidation of Carbon−Hydrogen Bonds (original) (raw)

Copper-Catalyzed Aliphatic C–H Amination with an Amidine Moiety

Organic Letters, 2013

A method for amination of aliphatic CÀH bonds of N-alkylamidines is described that utilizes Cu(OAc) 2 as the catalyst in the presence of PhI(OAc) 2 and K 3 PO 4. The resulting products, dihydroimidazoles and tetrahydropyrimidines, could be converted into the corresponding diamines by hydride reduction.

Catalytic CH Amination with Unactivated Amines through Copper(II) Amides

Angewandte Chemie International Edition, 2010

Alexander von Humboldt Foundation (re-invitation award to T.H.W.), and the Chemical Computing Group (MOE software to T.R.C.). Y.M.B. thanks Georgetown University for a Dissertation Fellowship and M.M.M. is grateful to the Luce Foundation for a predoctoral fellowship.

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

Organometallics, 2010

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 ligandaccelerated 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 R-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 ringopened 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)-CudNSO 2 R] þ. 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 (ΔG ‡ = 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.

Efficient Copper-Catalyzed Multicomponent Synthesis of N-Acyl Amidines via Acyl Nitrenes

Journal of the American Chemical Society, 2019

Direct synthetic routes to amidines are desired, as they are widely present in many biologically active compounds and organometallic complexes. N-Acyl amidines in particular can be used as a starting material for the synthesis of heterocycles and have several other applications. Here, we describe a fast and practical copper-catalyzed three-component reaction of aryl acetylenes, amines, and easily accessible 1,4,2-dioxazol-5-ones to N-acyl amidines, generating CO 2 as the only byproduct. Transformation of the dioxazolones on the Cu catalyst generates acyl nitrenes that rapidly insert into the copper acetylide Cu−C bond rather than undergoing an undesired Curtius rearrangement. For nonaromatic dioxazolones, [Cu(OAc)(Xantphos)] is a superior catalyst for this transformation, leading to full substrate conversion within 10 min. For the direct synthesis of N-benzoyl amidine derivatives from aromatic dioxazolones, [Cu(OAc)(Xantphos)] proved to be inactive, but moderate to good yields were obtained when using simple copper(I) iodide (CuI) as the catalyst. Mechanistic studies revealed the aerobic instability of one of the intermediates at low catalyst loadings, but the reaction could still be performed in air for most substrates when using catalyst loadings of 5 mol %. The herein reported procedure not only provides a new, practical, and direct route to N-acyl amidines but also represents a new type of C−N bond formation.